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Sample records for adult mammalian central

  1. Regeneration strategies after the adult mammalian central nervous system injury—biomaterials

    PubMed Central

    Gao, Yudan; Yang, Zhaoyang; Li, Xiaoguang

    2016-01-01

    The central nervous system (CNS) has very restricted intrinsic regeneration ability under the injury or disease condition. Innovative repair strategies, therefore, are urgently needed to facilitate tissue regeneration and functional recovery. The published tissue repair/regeneration strategies, such as cell and/or drug delivery, has been demonstrated to have some therapeutic effects on experimental animal models, but can hardly find clinical applications due to such methods as the extremely low survival rate of transplanted cells, difficulty in integrating with the host or restriction of blood–brain barriers to administration patterns. Using biomaterials can not only increase the survival rate of grafts and their integration with the host in the injured CNS area, but also sustainably deliver bioproducts to the local injured area, thus improving the microenvironment in that area. This review mainly introduces the advances of various strategies concerning facilitating CNS regeneration. PMID:27047678

  2. Nitric oxide negatively regulates mammalian adult neurogenesis

    NASA Astrophysics Data System (ADS)

    Packer, Michael A.; Stasiv, Yuri; Benraiss, Abdellatif; Chmielnicki, Eva; Grinberg, Alexander; Westphal, Heiner; Goldman, Steven A.; Enikolopov, Grigori

    2003-08-01

    Neural progenitor cells are widespread throughout the adult central nervous system but only give rise to neurons in specific loci. Negative regulators of neurogenesis have therefore been postulated, but none have yet been identified as subserving a significant role in the adult brain. Here we report that nitric oxide (NO) acts as an important negative regulator of cell proliferation in the adult mammalian brain. We used two independent approaches to examine the function of NO in adult neurogenesis. In a pharmacological approach, we suppressed NO production in the rat brain by intraventricular infusion of an NO synthase inhibitor. In a genetic approach, we generated a null mutant neuronal NO synthase knockout mouse line by targeting the exon encoding active center of the enzyme. In both models, the number of new cells generated in neurogenic areas of the adult brain, the olfactory subependyma and the dentate gyrus, was strongly augmented, which indicates that division of neural stem cells in the adult brain is controlled by NO and suggests a strategy for enhancing neurogenesis in the adult central nervous system.

  3. Evidence for an Age-Dependent Decline in Axon Regeneration in the Adult Mammalian Central Nervous System.

    PubMed

    Geoffroy, Cédric G; Hilton, Brett J; Tetzlaff, Wolfram; Zheng, Binhai

    2016-04-12

    How aging impacts axon regeneration after CNS injury is not known. We assessed the impact of age on axon regeneration induced by Pten deletion in corticospinal and rubrospinal neurons, two neuronal populations with distinct innate regenerative abilities. As in young mice, Pten deletion in older mice remains effective in preventing axotomy-induced decline in neuron-intrinsic growth state, as assessed by mTOR activity, neuronal soma size, and axonal growth proximal to a spinal cord injury. However, axonal regeneration distal to injury is greatly diminished, accompanied by increased expression of astroglial and inflammatory markers at the injury site. Thus, the mammalian CNS undergoes an age-dependent decline in axon regeneration, as revealed when neuron-intrinsic growth state is elevated. These results have important implications for developing strategies to promote axonal repair after CNS injuries or diseases, which increasingly affect middle-aged to aging populations. PMID:27050519

  4. Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

    ERIC Educational Resources Information Center

    Drew, Liam J.; Fusi, Stefano; Hen, René

    2013-01-01

    In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

  5. Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain.

    PubMed

    Feliciano, David M; Bordey, Angélique; Bonfanti, Luca

    2015-10-01

    Two decades after the discovery that neural stem cells (NSCs) populate some regions of the mammalian central nervous system (CNS), deep knowledge has been accumulated on their capacity to generate new neurons in the adult brain. This constitutive adult neurogenesis occurs throughout life primarily within remnants of the embryonic germinal layers known as "neurogenic sites." Nevertheless, some processes of neurogliogenesis also occur in the CNS parenchyma commonly considered as "nonneurogenic." This "noncanonical" cell genesis has been the object of many claims, some of which turned out to be not true. Indeed, it is often an "incomplete" process as to its final outcome, heterogeneous by several measures, including regional location, progenitor identity, and fate of the progeny. These aspects also strictly depend on the animal species, suggesting that persistent neurogenic processes have uniquely adapted to the brain anatomy of different mammals. Whereas some examples of noncanonical neurogenesis are strictly parenchymal, others also show stem cell niche-like features and a strong link with the ventricular cavities. This work will review results obtained in a research field that expanded from classic neurogenesis studies involving a variety of areas of the CNS outside of the subventricular zone (SVZ) and subgranular zone (SGZ). It will be highlighted how knowledge concerning noncanonical neurogenic areas is still incomplete owing to its regional and species-specific heterogeneity, and to objective difficulties still hampering its full identification and characterization. PMID:26384869

  6. Towards regenerating the mammalian heart: challenges in evaluating experimentally induced adult mammalian cardiomyocyte proliferation.

    PubMed

    Zebrowski, David C; Becker, Robert; Engel, Felix B

    2016-05-01

    In recent years, there has been a dramatic increase in research aimed at regenerating the mammalian heart by promoting endogenous cardiomyocyte proliferation. Despite many encouraging successes, it remains unclear if we are any closer to achieving levels of mammalian cardiomyocyte proliferation for regeneration as seen during zebrafish regeneration. Furthermore, current cardiac regenerative approaches do not clarify whether the induced cardiomyocyte proliferation is an epiphenomena or responsible for the observed improvement in cardiac function. Moreover, due to the lack of standardized protocols to determine cardiomyocyte proliferation in vivo, it remains unclear if one mammalian regenerative factor is more effective than another. Here, we discuss current methods to identify and evaluate factors for the induction of cardiomyocyte proliferation and challenges therein. Addressing challenges in evaluating adult cardiomyocyte proliferation will assist in determining 1) which regenerative factors should be pursued in large animal studies; 2) if a particular level of cell cycle regulation presents a better therapeutic target than another (e.g., mitogenic receptors vs. cyclins); and 3) which combinatorial approaches offer the greatest likelihood of success. As more and more regenerative studies come to pass, progress will require a system that not only can evaluate efficacy in an objective manner but can also consolidate observations in a meaningful way. PMID:26921436

  7. Adult neurogenesis in the mammalian hippocampus: Why the dentate gyrus?

    PubMed Central

    Drew, Liam J.; Fusi, Stefano; Hen, René

    2013-01-01

    In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity after the perinatal period suggests that unique aspects of the structure and function of DG and olfactory bulb circuits allow them to benefit from the adult generation of neurons. In this review, we consider the distinctive features of the DG that may account for it being able to profit from this singular form of neural plasticity. Approaches to the problem of neurogenesis are grouped as “bottom-up,” where the phenotype of adult-born granule cells is contrasted to that of mature developmentally born granule cells, and “top-down,” where the impact of altering the amount of neurogenesis on behavior is examined. We end by considering the primary implications of these two approaches and future directions. PMID:24255101

  8. Epicardial FSTL1 reconstitution regenerates the adult mammalian heart

    PubMed Central

    Wei, Ke; Serpooshan, Vahid; Hurtado, Cecilia; Diez-Cuñado, Marta; Zhao, Mingming; Maruyama, Sonomi; Zhu, Wenhong; Fajardo, Giovanni; Noseda, Michela; Nakamura, Kazuto; Tian, Xueying; Liu, Qiaozhen; Wang, Andrew; Matsuura, Yuka; Bushway, Paul; Cai, Wenqing; Savchenko, Alex; Mahmoudi, Morteza; Schneider, Michael D.; van den Hoff, Maurice J. B.; Butte, Manish J.; Yang, Phillip C.; Walsh, Kenneth; Zhou, Bin; Bernstein, Daniel; Mercola, Mark; Ruiz-Lozano, Pilar

    2016-01-01

    The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin-like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1) via an epicardial patch stimulates cell cycle entry and division of pre-existing cardiomyocytes, improving cardiac function and survival in mouse and swine models of myocardial infarction. The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans. PMID:26375005

  9. Epicardial FSTL1 reconstitution regenerates the adult mammalian heart.

    PubMed

    Wei, Ke; Serpooshan, Vahid; Hurtado, Cecilia; Diez-Cuñado, Marta; Zhao, Mingming; Maruyama, Sonomi; Zhu, Wenhong; Fajardo, Giovanni; Noseda, Michela; Nakamura, Kazuto; Tian, Xueying; Liu, Qiaozhen; Wang, Andrew; Matsuura, Yuka; Bushway, Paul; Cai, Wenqing; Savchenko, Alex; Mahmoudi, Morteza; Schneider, Michael D; van den Hoff, Maurice J B; Butte, Manish J; Yang, Phillip C; Walsh, Kenneth; Zhou, Bin; Bernstein, Daniel; Mercola, Mark; Ruiz-Lozano, Pilar

    2015-09-24

    The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin-like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1) via an epicardial patch stimulates cell cycle entry and division of pre-existing cardiomyocytes, improving cardiac function and survival in mouse and swine models of myocardial infarction. The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans. PMID:26375005

  10. Beneficial effects of x-irradiation on recovery of lesioned mammalian central nervous tissue

    SciTech Connect

    Kalderon, N.; Alfieri, A.A.; Fuks, Z. )

    1990-12-01

    We examined the potential of x-irradiation, at clinical dose levels, to manipulate the cellular constituents and thereby change the consequences of transection injury to adult mammalian central nervous tissue (rat olfactory bulb). Irradiation resulted in reduction or elimination of reactive astrocytes at the site of incision provided that it was delivered within a defined time window postinjury. Under conditions optimal for the elimination of gliosis (15-18 days postinjury), irradiation of severed olfactory bulbs averted some of the degenerative consequences of lesion. We observed that irradiation was accompanied by prevention of tissue degeneration around the site of lesion, structural healing with maintenance of the typical cell lamination, and rescue of some axotomized mitral cells (principal bulb neurons). Thus radiation resulted in partial preservation of normal tissue morphology. It is postulated that intrusive cell populations are generated in response to injury and reactive astrocytes are one such group. Our results suggest that selective elimination of these cells by irradiation enabled some of the regenerative processes that are necessary for full recovery to maintain their courses. The cellular targets of these cells, their modes of intervention in recovery, and the potential role of irradiation as a therapeutic modality for injured central nervous system are discussed.

  11. The Social Environment and Neurogenesis in the Adult Mammalian Brain

    PubMed Central

    Lieberwirth, Claudia; Wang, Zuoxin

    2012-01-01

    Adult neurogenesis – the formation of new neurons in adulthood – has been shown to be modulated by a variety of endogenous (e.g., trophic factors, neurotransmitters, and hormones) as well as exogenous (e.g., physical activity and environmental complexity) factors. Research on exogenous regulators of adult neurogenesis has focused primarily on the non-social environment. More recently, however, evidence has emerged suggesting that the social environment can also affect adult neurogenesis. The present review details the effects of adult–adult (e.g., mating and chemosensory interactions) and adult–offspring (e.g., gestation, parenthood, and exposure to offspring) interactions on adult neurogenesis. In addition, the effects of a stressful social environment (e.g., lack of social support and dominant–subordinate interactions) on adult neurogenesis are reviewed. The underlying hormonal mechanisms and potential functional significance of adult-generated neurons in mediating social behaviors are also discussed. PMID:22586385

  12. Seasonal regulation of structural plasticity and neurogenesis in the adult mammalian brain: focus on the sheep hypothalamus.

    PubMed

    Migaud, Martine; Butrille, Lucile; Batailler, Martine

    2015-04-01

    To cope with variations in the environment, most mammalian species exhibit seasonal cycles in physiology and behaviour. Seasonal plasticity during the lifetime contributes to seasonal physiology. Over the years, our ideas regarding adult brain plasticity and, more specifically, hypothalamic plasticity have greatly evolved. Along with the two main neurogenic regions, namely the hippocampal subgranular and lateral ventricle subventricular zones, the hypothalamus, which is the central homeostatic regulator of numerous physiological functions that comprise sexual behaviours, feeding and metabolism, also hosts neurogenic niches. Both endogenous and exogenous factors, including the photoperiod, modulate the hypothalamic neurogenic capacities. The present review describes the effects of season on adult morphological plasticity and neurogenesis in seasonal species, for which the photoperiod is a master environmental cue for the successful programming of seasonal functions. In addition, the potential functional significance of adult neurogenesis in the mediation of the seasonal control of reproduction and feeding is discussed. PMID:25462590

  13. Development-Inspired Reprogramming of the Mammalian Central Nervous System

    PubMed Central

    Amamoto, Ryoji; Arlotta, Paola

    2014-01-01

    In 2012, John Gurdon and Shinya Yamanaka shared the Nobel Prize for the exciting demonstration that the identity of differentiated cells is not irreversibly determined but can be changed back to a pluripotent state under appropriate instructive signals. The principle that differentiated cells can revert to an embryonic state and even be converted directly from one cell-type into another not only turns fundamental principles of development on their head but also has profound implications for regenerative medicine. Replacement of diseased tissue with newly reprogrammed cells and modeling of human disease are concrete opportunities. Here, we focus on the central nervous system to consider whether and how reprogramming of cell identity may impact regeneration and modeling of a system historically considered immutable and hardwired. PMID:24482482

  14. Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function.

    PubMed

    Garza-Lombó, Carla; Gonsebatt, María E

    2016-01-01

    The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

  15. Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function

    PubMed Central

    Garza-Lombó, Carla; Gonsebatt, María E.

    2016-01-01

    The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

  16. Potential for neural regeneration after neurotoxic injury in the adult mammalian retina

    NASA Astrophysics Data System (ADS)

    Ooto, Sotaro; Akagi, Tadamichi; Kageyama, Ryoichiro; Akita, Joe; Mandai, Michiko; Honda, Yoshihito; Takahashi, Masayo

    2004-09-01

    It has long been believed that the retina of mature mammals is incapable of regeneration. In this study, using the N-methyl-D-aspartate neurotoxicity model of adult rat retina, we observed that some Müller glial cells were stimulated to proliferate in response to a toxic injury and produce bipolar cells and rod photoreceptors. Although these newly produced neurons were limited in number, retinoic acid treatment promoted the number of regenerated bipolar cells. Moreover, misexpression of basic helix-loop-helix and homeobox genes promoted the induction of amacrine, horizontal, and rod photoreceptor specific phenotypes. These findings demonstrated that retinal neurons regenerated even in adult mammalian retina after toxic injury. Furthermore, we could partially control the fate of the regenerated neurons with extrinsic factors or intrinsic genes. The Müller glial cells constitute a potential source for the regeneration of adult mammalian retina and can be a target for drug delivery and gene therapy in retinal degenerative diseases.

  17. ssiRNA Induced Gene Silencing is Transmitted Between Cells From the Mammalian Central Nervous System

    PubMed Central

    Zhao, Tian-Yong; Zou, Shi-Ping; Alimova, Yelena V.; Wang, Guoying; Hauser, Kurt F.; Ghandour, M. Said; Knapp, Pamela E.

    2014-01-01

    Although siRNA induced gene silencing can be transmitted between cells in plants and in C. elegans, this phenomenon has been barely studied in mammalian cells. Both immortalized oligodendrocytes and SNB-19 glioblastoma cells were transfected with siRNA constructs for PTEN (phosphatase and tensin homolog deleted on chromosome 10) or Akt (Akt/protein kinase B). Co-cultures were established between silenced cells and non-silenced cells which were hygromycin resistant and/or expressed green fluorescent protein (GFP). After fluorescence sorting or hygromycin selection to remove the silenced cells, the expression of PTEN or Akt genes in the originally unsilenced cells was in all cases significantly decreased. Importantly, silencing did not occur in transwell culture studies, suggesting that transmission of the silencing signal requires a close association between cells. These results provide the first direct demonstration that an siRNA induced silencing signal can be transmitted between mammalian central nervous system (CNS) cells. PMID:16923165

  18. Disrupted in schizophrenia 1 and synaptic function in the mammalian central nervous system

    PubMed Central

    Randall, Andrew D; Kurihara, Mai; Brandon, Nicholas J; Brown, Jon T

    2014-01-01

    The disrupted in schizophrenia 1 (DISC1) gene is found at the breakpoint of an inherited chromosomal translocation, and segregates with major mental illnesses. Its potential role in central nervous system (CNS) malfunction has triggered intensive investigation of the biological roles played by DISC1, with the hope that this may shed new light on the pathobiology of psychiatric disease. Such work has ranged from investigations of animal behavior to detailed molecular-level analysis of the assemblies that DISC1 forms with other proteins. Here, we discuss the evidence for a role of DISC1 in synaptic function in the mammalian CNS. PMID:24712987

  19. Disrupted in schizophrenia 1 and synaptic function in the mammalian central nervous system.

    PubMed

    Randall, Andrew D; Kurihara, Mai; Brandon, Nicholas J; Brown, Jon T

    2014-04-01

    The disrupted in schizophrenia 1 (DISC1) gene is found at the breakpoint of an inherited chromosomal translocation, and segregates with major mental illnesses. Its potential role in central nervous system (CNS) malfunction has triggered intensive investigation of the biological roles played by DISC1, with the hope that this may shed new light on the pathobiology of psychiatric disease. Such work has ranged from investigations of animal behavior to detailed molecular-level analysis of the assemblies that DISC1 forms with other proteins. Here, we discuss the evidence for a role of DISC1 in synaptic function in the mammalian CNS. PMID:24712987

  20. Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia.

    PubMed Central

    Lois, C; Alvarez-Buylla, A

    1993-01-01

    Subventricular zone (SVZ) cells proliferate spontaneously in vivo in the telencephalon of adult mammals. Several studies suggest that SVZ cells do not differentiate after mitosis into neurons or glia but die. In the present work, we show that SVZ cells labeled in the brains of adult mice with [3H]thymidine differentiate directly into neurons and glia in explant cultures. In vitro labeling with [3H]thymidine shows that 98% of the neurons that differentiate from the SVZ explants are derived from precursor cells that underwent their last division in vivo. This report identifies the SVZ cells as neuronal precursors in an adult mammalian brain. Images Fig. 1 Fig. 2 Fig. 3 PMID:8446631

  1. The Intrinsic Electrophysiological Properties of Mammalian Neurons: Insights into Central Nervous System Function

    NASA Astrophysics Data System (ADS)

    Llinas, Rodolfo R.

    1988-12-01

    This article reviews the electroresponsive properties of single neurons in the mammalian central nervous system (CNS). In some of these cells the ionic conductances responsible for their excitability also endow them with autorhythmic electrical oscillatory properties. Chemical or electrical synaptic contacts between these neurons often result in network oscillations. In such networks, autorhytmic neurons may act as true oscillators (as pacemakers) or as resonators (responding preferentially to certain firing frequencies). Oscillations and resonance in the CNS are proposed to have diverse functional roles, such as (i) determining global functional states (for example, sleep-wakefulness or attention), (ii) timing in motor coordination, and (iii) specifying connectivity during development. Also, oscillation, especially in the thalamo-cortical circuits, may be related to certain neurological and psychiatric disorders. This review proposes that the autorhythmic electrical properties of central neurons and their connectivity form the basis for an intrinsic functional coordinate system that provides internal context to sensory input.

  2. Holocene mammalian change in the central Columbia Basin of eastern Washington state, USA

    NASA Astrophysics Data System (ADS)

    Lyman, R. Lee

    2016-08-01

    Predictions of changes in the Holocene mammalian fauna of the central Columbia Basin in eastern Washington (USA) based on environmental changes are largely met. Taxonomic richness is greatest during periods of cool-moist climate. Rates of input of faunal remains to the paleozoological record may suggest greater mammalian biomass during periods of greater moisture but are difficult to interpret without data on sampling intensity in the form of volume of sediment excavated. Abundances of leporids and grazing ungulates fluctuate in concert with abundance of grass. Several biogeographic records are tantalizing but require additional study and data before being accepted as valid. Records of red fox (Vulpes vulpes) indicate this species was present in the central basin during the Holocene contrary to historic records and recent suggestions modern foxes there are escapees from fur farms. Bison (Bison bison) and bighorn sheep (Ovis canadensis) underwent diminution of body size during the Holocene. Modern efforts to conserve the Columbia Basin ecosystem are advised to consider the Holocene record as indicative of what may happen to that ecosystem in the future.

  3. Control of adult neurogenesis by programmed cell death in the mammalian brain.

    PubMed

    Ryu, Jae Ryun; Hong, Caroline Jeeyeon; Kim, Joo Yeon; Kim, Eun-Kyoung; Sun, Woong; Yu, Seong-Woon

    2016-01-01

    The presence of neural stem cells (NSCs) and the production of new neurons in the adult brain have received great attention from scientists and the public because of implications to brain plasticity and their potential use for treating currently incurable brain diseases. Adult neurogenesis is controlled at multiple levels, including proliferation, differentiation, migration, and programmed cell death (PCD). Among these, PCD is the last and most prominent process for regulating the final number of mature neurons integrated into neural circuits. PCD can be classified into apoptosis, necrosis, and autophagic cell death and emerging evidence suggests that all three may be important modes of cell death in neural stem/progenitor cells. However, the molecular mechanisms that regulate PCD and thereby impact the intricate balance between self-renewal, proliferation, and differentiation during adult neurogenesis are not well understood. In this comprehensive review, we focus on the extent, mechanism, and biological significance of PCD for the control of adult neurogenesis in the mammalian brain. The role of intrinsic and extrinsic factors in the regulation of PCD at the molecular and systems levels is also discussed. Adult neurogenesis is a dynamic process, and the signals for differentiation, proliferation, and death of neural progenitor/stem cells are closely interrelated. A better understanding of how adult neurogenesis is influenced by PCD will help lead to important insights relevant to brain health and diseases. PMID:27098178

  4. Lentiviral vectors as tools to understand central nervous system biology in mammalian model organisms

    PubMed Central

    Parr-Brownlie, Louise C.; Bosch-Bouju, Clémentine; Schoderboeck, Lucia; Sizemore, Rachel J.; Abraham, Wickliffe C.; Hughes, Stephanie M.

    2015-01-01

    Lentiviruses have been extensively used as gene delivery vectors since the mid-1990s. Usually derived from the human immunodeficiency virus genome, they mediate efficient gene transfer to non-dividing cells, including neurons and glia in the adult mammalian brain. In addition, integration of the recombinant lentiviral construct into the host genome provides permanent expression, including the progeny of dividing neural precursors. In this review, we describe targeted vectors with modified envelope glycoproteins and expression of transgenes under the regulation of cell-selective and inducible promoters. This technology has broad utility to address fundamental questions in neuroscience and we outline how this has been used in rodents and primates. Combining viral tract tracing with immunohistochemistry and confocal or electron microscopy, lentiviral vectors provide a tool to selectively label and trace specific neuronal populations at gross or ultrastructural levels. Additionally, new generation optogenetic technologies can be readily utilized to analyze neuronal circuit and gene functions in the mature mammalian brain. Examples of these applications, limitations of current systems and prospects for future developments to enhance neuroscience knowledge will be reviewed. Finally, we will discuss how these vectors may be translated from gene therapy trials into the clinical setting. PMID:26041987

  5. Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family

    PubMed Central

    Porrello, Enzo R.; Mahmoud, Ahmed I.; Simpson, Emma; Johnson, Brett A.; Grinsfelder, David; Canseco, Diana; Mammen, Pradeep P.; Rothermel, Beverly A.; Olson, Eric N.; Sadek, Hesham A.

    2013-01-01

    We recently identified a brief time period during postnatal development when the mammalian heart retains significant regenerative potential after amputation of the ventricular apex. However, one major unresolved question is whether the neonatal mouse heart can also regenerate in response to myocardial ischemia, the most common antecedent of heart failure in humans. Here, we induced ischemic myocardial infarction (MI) in 1-d-old mice and found that this results in extensive myocardial necrosis and systolic dysfunction. Remarkably, the neonatal heart mounted a robust regenerative response, through proliferation of preexisting cardiomyocytes, resulting in full functional recovery within 21 d. Moreover, we show that the miR-15 family of microRNAs modulates neonatal heart regeneration through inhibition of postnatal cardiomyocyte proliferation. Finally, we demonstrate that inhibition of the miR-15 family from an early postnatal age until adulthood increases myocyte proliferation in the adult heart and improves left ventricular systolic function after adult MI. We conclude that the neonatal mammalian heart can regenerate after myocardial infarction through proliferation of preexisting cardiomyocytes and that the miR-15 family contributes to postnatal loss of cardiac regenerative capacity. PMID:23248315

  6. Imaging single synaptic vesicles in Mammalian central synapses with quantum dots.

    PubMed

    Zhang, Qi

    2013-01-01

    This protocol describes a sensitive and rigorous method to monitor the movement and turnover of single synaptic vesicles in live presynaptic terminals of mammalian central nervous system. This technique makes use of Photoluminescent semiconductor nanocrystals, quantum dots (Qdots), by their nanometer size, superior photoproperties, and pH-sensitivity. In comparison with previous fluorescent probes like styryl dyes and pH-sensitive fluorescent proteins, Qdots offer strict loading ratio, multi-modality detection, single vesicle precision, and most importantly distinctive signals for different modes of vesicle fusion. Qdots are spectrally compatible with existing fluorescent probes for synaptic vesicles and thus allow multichannel -imaging. With easy modification, this technique can be applied to other types of synapses and cells. PMID:23494380

  7. Animal Models for Investigating the Central Control of the Mammalian Diving Response

    PubMed Central

    McCulloch, Paul Frederick

    2012-01-01

    Pioneering studies by Per Scholander indicated that the diving response consists of reflexly induced apnea, bradycardia and an alteration of blood flow that maintains perfusion of the heart and brain. More recently field physiological studies have shown that many marine animals can adjust cardiorespiratory aspects of their diving response depending upon the behavioral situation. This could suggest that the very labile heart rate during diving is under direct cortical control. However, the final control of autonomic nervous system functioning resides within the brainstem and not the cortex. Many physiologists regard the brain as a “black box” where important neuronal functioning occurs, but the complexity of such functioning leaves systematic investigation a daunting task. As a consequence the central control of the diving response has been under-investigated. Thus, to further advance the field of diving physiology by understanding its central neuronal control, it would be first necessary to understand the reflex circuitry that exists within the brainstem of diving animals. To do this will require an appropriate animal model. In this review, two animals, the muskrat and rat, will be offered as animal models to investigate the central aspects of the diving response. Firstly, although these rodents are not marine animals, natural histories indicate that both animals can and do exploit aquatic environments. Secondly, physiological recordings during natural and simulated diving indicate that both animals possess the same basic physiological responses to underwater submersion that occur in marine animals. Thirdly, the size and ease of housing of both animals makes them attractive laboratory research animals. Finally, the enormous amount of scientific literature regarding rodent brainstem autonomic control mechanisms, and the availability of brain atlases, makes these animals ideal choices to study the central control of the mammalian diving response. PMID:22661956

  8. Animal models for investigating the central control of the Mammalian diving response.

    PubMed

    McCulloch, Paul Frederick

    2012-01-01

    Pioneering studies by Per Scholander indicated that the diving response consists of reflexly induced apnea, bradycardia and an alteration of blood flow that maintains perfusion of the heart and brain. More recently field physiological studies have shown that many marine animals can adjust cardiorespiratory aspects of their diving response depending upon the behavioral situation. This could suggest that the very labile heart rate during diving is under direct cortical control. However, the final control of autonomic nervous system functioning resides within the brainstem and not the cortex. Many physiologists regard the brain as a "black box" where important neuronal functioning occurs, but the complexity of such functioning leaves systematic investigation a daunting task. As a consequence the central control of the diving response has been under-investigated. Thus, to further advance the field of diving physiology by understanding its central neuronal control, it would be first necessary to understand the reflex circuitry that exists within the brainstem of diving animals. To do this will require an appropriate animal model. In this review, two animals, the muskrat and rat, will be offered as animal models to investigate the central aspects of the diving response. Firstly, although these rodents are not marine animals, natural histories indicate that both animals can and do exploit aquatic environments. Secondly, physiological recordings during natural and simulated diving indicate that both animals possess the same basic physiological responses to underwater submersion that occur in marine animals. Thirdly, the size and ease of housing of both animals makes them attractive laboratory research animals. Finally, the enormous amount of scientific literature regarding rodent brainstem autonomic control mechanisms, and the availability of brain atlases, makes these animals ideal choices to study the central control of the mammalian diving response. PMID:22661956

  9. Overview of Central Auditory Processing Deficits in Older Adults.

    PubMed

    Atcherson, Samuel R; Nagaraj, Naveen K; Kennett, Sarah E W; Levisee, Meredith

    2015-08-01

    Although there are many reported age-related declines in the human body, the notion that a central auditory processing deficit exists in older adults has not always been clear. Hearing loss and both structural and functional central nervous system changes with advancing age are contributors to how we listen, hear, and process auditory information. Even older adults with normal or near normal hearing sensitivity may exhibit age-related central auditory processing deficits as measured behaviorally and/or electrophysiologically. The purpose of this article is to provide an overview of assessment and rehabilitative approaches for central auditory processing deficits in older adults. It is hoped that the outcome of the information presented here will help clinicians with older adult patients who do not exhibit the typical auditory processing behaviors exhibited by others at the same age and with comparable hearing sensitivity all in the absence of other health-related conditions. PMID:27516715

  10. Overview of Central Auditory Processing Deficits in Older Adults

    PubMed Central

    Atcherson, Samuel R.; Nagaraj, Naveen K.; Kennett, Sarah E.W.; Levisee, Meredith

    2015-01-01

    Although there are many reported age-related declines in the human body, the notion that a central auditory processing deficit exists in older adults has not always been clear. Hearing loss and both structural and functional central nervous system changes with advancing age are contributors to how we listen, hear, and process auditory information. Even older adults with normal or near normal hearing sensitivity may exhibit age-related central auditory processing deficits as measured behaviorally and/or electrophysiologically. The purpose of this article is to provide an overview of assessment and rehabilitative approaches for central auditory processing deficits in older adults. It is hoped that the outcome of the information presented here will help clinicians with older adult patients who do not exhibit the typical auditory processing behaviors exhibited by others at the same age and with comparable hearing sensitivity all in the absence of other health-related conditions. PMID:27516715

  11. The neonate versus adult mammalian immune system in cardiac repair and regeneration.

    PubMed

    Sattler, Susanne; Rosenthal, Nadia

    2016-07-01

    The immune system is a crucial player in tissue homeostasis and wound healing. A sophisticated cascade of events triggered upon injury ensures protection from infection and initiates and orchestrates healing. While the neonatal mammal can readily regenerate damaged tissues, adult regenerative capacity is limited to specific tissue types, and in organs such as the heart, adult wound healing results in fibrotic repair and loss of function. Growing evidence suggests that the immune system greatly influences the balance between regeneration and fibrotic repair. The neonate mammalian immune system has impaired pro-inflammatory function, is prone to T-helper type 2 responses and has an immature adaptive immune system skewed towards regulatory T cells. While these characteristics make infants susceptible to infection and prone to allergies, it may also provide an immunological environment permissive of regeneration. In this review we will give a comprehensive overview of the immune cells involved in healing and regeneration of the heart and explore differences between the adult and neonate immune system that may explain differences in regenerative ability. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID:26801961

  12. [Proliferation of adult mammalian ventricular cardiomyocytes: a sporadic but feasible phenomenon].

    PubMed

    Vargas-González, Alvaro

    2014-01-01

    Proliferation of adult mammalian ventricular cardiomyocytes has been ruled out by some researchers, who have argued that these cells are terminally differentiated; however, this dogma has been rejected because other researchers have reported that these cells can present the processes necessary to proliferate, that is, DNA synthesis, mitosis and cytokinesis when the heart is damaged experimentally through pharmacological and surgical strategies or due to pathological conditions concerning the cardiovascular system. This review integrates some of the available works in the literature evaluating the DNA synthesis, mitosis and cytokinesis in these myocytes, when the myocardium is damaged, with the purpose of knowing if their proliferation can be considered as a feasible phenomenon. The review is concluded with a reflection about the perspectives of the knowledge generated in this area. PMID:24792902

  13. Scanning Electron Microscopy Reveals Two Distinct Classes of Erythroblastic Island Isolated from Adult Mammalian Bone Marrow.

    PubMed

    Yeo, Jia Hao; McAllan, Bronwyn M; Fraser, Stuart T

    2016-04-01

    Erythroblastic islands are multicellular clusters in which a central macrophage supports the development and maturation of red blood cell (erythroid) progenitors. These clusters play crucial roles in the pathogenesis observed in animal models of hematological disorders. The precise structure and function of erythroblastic islands is poorly understood. Here, we have combined scanning electron microscopy and immuno-gold labeling of surface proteins to develop a better understanding of the ultrastructure of these multicellular clusters. The erythroid-specific surface antigen Ter-119 and the transferrin receptor CD71 exhibited distinct patterns of protein sorting during erythroid cell maturation as detected by immuno-gold labeling. During electron microscopy analysis we observed two distinct classes of erythroblastic islands. The islands varied in size and morphology, and the number and type of erythroid cells interacting with the central macrophage. Assessment of femoral marrow isolated from a cavid rodent species (guinea pig, Cavis porcellus) and a marsupial carnivore species (fat-tailed dunnarts, Sminthopsis crassicaudata) showed that while the morphology of the central macrophage varied, two different types of erythroblastic islands were consistently identifiable. Our findings suggest that these two classes of erythroblastic islands are conserved in mammalian evolution and may play distinct roles in red blood cell production. PMID:26898901

  14. Cholesterol Regulates Multiple Forms of Vesicle Endocytosis at a Mammalian Central Synapse

    PubMed Central

    Yue, Hai-Yuan; Xu, Jianhua

    2015-01-01

    Endocytosis in synapses sustains neurotransmission by recycling vesicle membrane and maintaining the homeostasis of synaptic membrane. A role of membrane cholesterol in synaptic endocytosis remains controversial because of conflicting observations, technical limitations in previous studies, and potential interference from nonspecific effects after cholesterol manipulation. Furthermore, it is unclear whether cholesterol participates in distinct forms of endocytosis that function under different activity levels. In this study, applying the whole-cell membrane capacitance measurement to monitor endocytosis in real time at the rat calyx of Held terminals, we found that disrupting cholesterol with dialysis of cholesterol oxidase (COase) or methyl-β-cyclodextrin (MCD) impaired three different forms of endocytosis, i.e., slow endocytosis, rapid endocytosis, and endocytosis of the retrievable membrane that exists at the surface before stimulation. The effects were observed when disruption of cholesterol was mild enough not to change Ca2+ channel current or vesicle exocytosis, indicative of stringent cholesterol requirement in synaptic endocytosis. Extracting cholesterol with high concentrations of MCD reduced exocytosis, mainly by decreasing the readily releasable pool (RRP) and the vesicle replenishment after RRP depletion. Our study suggests that cholesterol is an important, universal regulator in multiple forms of vesicle endocytosis at mammalian central synapses. PMID:25893258

  15. Long-term, stable differentiation of human embryonic stem cell-derived neural precursors grafted into the adult mammalian neostriatum.

    PubMed

    Nasonkin, Igor; Mahairaki, Vasiliki; Xu, Leyan; Hatfield, Glen; Cummings, Brian J; Eberhart, Charles; Ryugo, David K; Maric, Dragan; Bar, Eli; Koliatsos, Vassilis E

    2009-10-01

    Stem cell grafts have been advocated as experimental treatments for neurological diseases by virtue of their ability to offer trophic support for injured neurons and, theoretically, to replace dead neurons. Human embryonic stem cells (HESCs) are a rich source of neural precursors (NPs) for grafting, but have been questioned for their tendency to form tumors. Here we studied the ability of HESC-derived NP grafts optimized for cell number and differentiation stage prior to transplantation, to survive and stably differentiate and integrate in the basal forebrain (neostriatum) of young adult nude rats over long periods of time (6 months). NPs were derived from adherent monolayer cultures of HESCs exposed to noggin. After transplantation, NPs showed a drastic reduction in mitotic activity and an avid differentiation into neurons that projected via major white matter tracts to a variety of forebrain targets. A third of NP-derived neurons expressed the basal forebrain-neostriatal marker dopamine-regulated and cyclic AMP-regulated phosphoprotein. Graft-derived neurons formed mature synapses with host postsynaptic structures, including dendrite shafts and spines. NPs inoculated in white matter tracts showed a tendency toward glial (primarily astrocytic) differentiation, whereas NPs inoculated in the ventricular epithelium persisted as nestin(+) precursors. Our findings demonstrate the long-term ability of noggin-derived human NPs to structurally integrate tumor-free into the mature mammalian forebrain, while maintaining some cell fate plasticity that is strongly influenced by particular central nervous system (CNS) niches. PMID:19609935

  16. Sodium currents activate without a Hodgkin-and-Huxley-type delay in central mammalian neurons.

    PubMed

    Baranauskas, Gytis; Martina, Marco

    2006-01-11

    Hodgkin and Huxley established that sodium currents in the squid giant axons activate after a delay, which is explained by the model of a channel with three identical independent gates that all have to open before the channel can pass current (the HH model). It is assumed that this model can adequately describe the sodium current activation time course in all mammalian central neurons, although there is no experimental evidence to support such a conjecture. We performed high temporal resolution studies of sodium currents gating in three types of central neurons. The results show that, within the tested voltage range from -55 to -35 mV, in all of these neurons, the activation time course of the current could be fit, after a brief delay, with a monoexponential function. The duration of delay from the start of the voltage command to the start of the extrapolated monoexponential fit was much smaller than predicted by the HH model. For example, in prefrontal cortex pyramidal neurons, at -46 mV and 12 degrees C, the observed average delay was 140 micros versus the 740 micros predicted by the two-gate HH model and the 1180 micros predicted by the three-gate HH model. These results can be explained by a model with two closed states and one open state. In this model, the transition between two closed states is approximately five times faster than the transition between the second closed state and the open state. This model captures all major properties of the sodium current activation. In addition, the proposed model reproduces the observed action potential shape more accurately than the traditional HH model. PMID:16407565

  17. Sensory Response of Transplanted Astrocytes in Adult Mammalian Cortex In Vivo.

    PubMed

    Zhang, Kuan; Chen, Chunhai; Yang, Zhiqi; He, Wenjing; Liao, Xiang; Ma, Qinlong; Deng, Ping; Lu, Jian; Li, Jingcheng; Wang, Meng; Li, Mingli; Zheng, Lianghong; Zhou, Zhuan; Sun, Wei; Wang, Liting; Jia, Hongbo; Yu, Zhengping; Zhou, Zhou; Chen, Xiaowei

    2016-09-01

    Glial precursor transplantation provides a potential therapy for brain disorders. Before its clinical application, experimental evidence needs to indicate that engrafted glial cells are functionally incorporated into the existing circuits and become essential partners of neurons for executing fundamental brain functions. While previous experiments supporting for their functional integration have been obtained under in vitro conditions using slice preparations, in vivo evidence for such integration is still lacking. Here, we utilized in vivo two-photon Ca(2+) imaging along with immunohistochemistry, fluorescent indicator labeling-based axon tracing and correlated light/electron microscopy to analyze the profiles and the functional status of glial precursor cell-derived astrocytes in adult mouse neocortex. We show that after being transplanted into somatosensory cortex, precursor-derived astrocytes are able to survive for more than a year and respond with Ca(2+) signals to sensory stimulation. These sensory-evoked responses are mediated by functionally-expressed nicotinic receptors and newly-established synaptic contacts with the host cholinergic afferents. Our results provide in vivo evidence for a functional integration of transplanted astrocytes into adult mammalian neocortex, representing a proof-of-principle for sensory cortex remodeling through addition of essential neural elements. Moreover, we provide strong support for the use of glial precursor transplantation to understand glia-related neural development in vivo. PMID:27405333

  18. Sensory Response of Transplanted Astrocytes in Adult Mammalian Cortex In Vivo

    PubMed Central

    Zhang, Kuan; Chen, Chunhai; Yang, Zhiqi; He, Wenjing; Liao, Xiang; Ma, Qinlong; Deng, Ping; Lu, Jian; Li, Jingcheng; Wang, Meng; Li, Mingli; Zheng, Lianghong; Zhou, Zhuan; Sun, Wei; Wang, Liting; Jia, Hongbo; Yu, Zhengping; Zhou, Zhou; Chen, Xiaowei

    2016-01-01

    Glial precursor transplantation provides a potential therapy for brain disorders. Before its clinical application, experimental evidence needs to indicate that engrafted glial cells are functionally incorporated into the existing circuits and become essential partners of neurons for executing fundamental brain functions. While previous experiments supporting for their functional integration have been obtained under in vitro conditions using slice preparations, in vivo evidence for such integration is still lacking. Here, we utilized in vivo two-photon Ca2+ imaging along with immunohistochemistry, fluorescent indicator labeling-based axon tracing and correlated light/electron microscopy to analyze the profiles and the functional status of glial precursor cell-derived astrocytes in adult mouse neocortex. We show that after being transplanted into somatosensory cortex, precursor-derived astrocytes are able to survive for more than a year and respond with Ca2+ signals to sensory stimulation. These sensory-evoked responses are mediated by functionally-expressed nicotinic receptors and newly-established synaptic contacts with the host cholinergic afferents. Our results provide in vivo evidence for a functional integration of transplanted astrocytes into adult mammalian neocortex, representing a proof-of-principle for sensory cortex remodeling through addition of essential neural elements. Moreover, we provide strong support for the use of glial precursor transplantation to understand glia-related neural development in vivo. PMID:27405333

  19. Alternative splicing contributes to K+ channel diversity in the mammalian central nervous system.

    PubMed Central

    Luneau, C J; Williams, J B; Marshall, J; Levitan, E S; Oliva, C; Smith, J S; Antanavage, J; Folander, K; Stein, R B; Swanson, R

    1991-01-01

    In an attempt to define the molecular basis of the functional diversity of K+ channels, we have isolated overlapping rat brain cDNAs that encoded a neuronal delayed rectifier K+ channel, K,4, that is structurally related to the Drosophila Shaw protein. Unlike previously characterized mammalian K+ channel genes, which each contain a single protein-coding exon, K,4 arises from alternative exon usage at a locus that also encodes another mammalian Shaw homolog, NGK2. Thus, the enormous diversity of K+ channels in mammals can be generated not just through gene duplication and divergence but also through alternative splicing of RNA. Images PMID:2023941

  20. Growth Arrest Specific 1 (GAS1) Is Abundantly Expressed in the Adult Mouse Central Nervous System

    PubMed Central

    Zarco, Natanael; Bautista, Elizabeth; Cuéllar, Manola; Vergara, Paula; Flores-Rodriguez, Paola; Aguilar-Roblero, Raúl

    2013-01-01

    Growth arrest specific 1 (GAS1) is a pleiotropic protein that induces apoptosis and cell arrest in different tumors, but it is also involved in the development of the nervous system and other tissues and organs. This dual ability is likely caused by its capacity to interact both by inhibiting the intracellular signaling cascade induced by glial cell-line derived neurotrophic factor and by facilitating the activity of the sonic hedgehog pathway. The presence of GAS1 mRNA has been described in adult mouse brain, and here we corroborated this observation. We then proceeded to determine the distribution of the protein in the adult central nervous system (CNS). We detected, by western blot analysis, expression of GAS1 in olfactory bulb, caudate-putamen, cerebral cortex, hippocampus, mesencephalon, medulla oblongata, cerebellum, and cervical spinal cord. To more carefully map the expression of GAS1, we performed double-label immunohistochemistry and noticed expression of GAS1 in neurons in all brain areas examined. We also observed expression of GAS1 in astroglial cells, albeit the pattern of expression was more restricted than that seen in neurons. Briefly, in the present article, we report the widespread distribution and cellular localization of the GAS1 native protein in adult mammalian CNS. PMID:23813868

  1. Leucine Zipper-bearing Kinase promotes axon growth in mammalian central nervous system neurons

    PubMed Central

    Chen, Meifan; Geoffroy, Cédric G.; Wong, Hetty N.; Tress, Oliver; Nguyen, Mallorie T.; Holzman, Lawrence B.; Jin, Yishi; Zheng, Binhai

    2016-01-01

    Leucine Zipper-bearing Kinase (LZK/MAP3K13) is a member of the mixed lineage kinase family with high sequence identity to Dual Leucine Zipper Kinase (DLK/MAP3K12). While DLK is established as a key regulator of axonal responses to injury, the role of LZK in mammalian neurons is poorly understood. By gain- and loss-of-function analyses in neuronal cultures, we identify LZK as a novel positive regulator of axon growth. LZK signals specifically through MKK4 and JNKs among MAP2Ks and MAPKs respectively in neuronal cells, with JNK activity positively regulating LZK protein levels. Neuronal maturation or activity deprivation activates the LZK-MKK4-JNK pathway. LZK and DLK share commonalities in signaling, regulation, and effects on axon extension. Furthermore, LZK-dependent regulation of DLK protein expression and the lack of additive effects on axon growth upon co-manipulation suggest complex functional interaction and cross-regulation between these two kinases. Together, our data support the possibility for two structurally related MAP3Ks to work in concert to mediate axonal responses to external insult or injury in mammalian CNS neurons. PMID:27511108

  2. Leucine Zipper-bearing Kinase promotes axon growth in mammalian central nervous system neurons.

    PubMed

    Chen, Meifan; Geoffroy, Cédric G; Wong, Hetty N; Tress, Oliver; Nguyen, Mallorie T; Holzman, Lawrence B; Jin, Yishi; Zheng, Binhai

    2016-01-01

    Leucine Zipper-bearing Kinase (LZK/MAP3K13) is a member of the mixed lineage kinase family with high sequence identity to Dual Leucine Zipper Kinase (DLK/MAP3K12). While DLK is established as a key regulator of axonal responses to injury, the role of LZK in mammalian neurons is poorly understood. By gain- and loss-of-function analyses in neuronal cultures, we identify LZK as a novel positive regulator of axon growth. LZK signals specifically through MKK4 and JNKs among MAP2Ks and MAPKs respectively in neuronal cells, with JNK activity positively regulating LZK protein levels. Neuronal maturation or activity deprivation activates the LZK-MKK4-JNK pathway. LZK and DLK share commonalities in signaling, regulation, and effects on axon extension. Furthermore, LZK-dependent regulation of DLK protein expression and the lack of additive effects on axon growth upon co-manipulation suggest complex functional interaction and cross-regulation between these two kinases. Together, our data support the possibility for two structurally related MAP3Ks to work in concert to mediate axonal responses to external insult or injury in mammalian CNS neurons. PMID:27511108

  3. Adult stem cells and mammalian epimorphic regeneration-insights from studying annual renewal of deer antlers.

    PubMed

    Li, Chunyi; Yang, Fuhe; Sheppard, Allan

    2009-09-01

    Mammalian organ regeneration is the "Holy Grail" of modern regenerative biology and medicine. The most dramatic organ replacement is known as epimorphic regeneration. To date our knowledge of epimorphic regeneration has come from studies of amphibians. Notably, these animals have the ability to reprogram phenotypically committed cells at the amputation plane toward an embryonic-like cell phenotype (dedifferentiation). The capability of mammals to initiate analogous regeneration, and whether similar mechanisms would be involved if it were to occur, remain unclear. Deer antlers are the only mammalian appendages capable of full renewal, and therefore offer a unique opportunity to explore how nature has solved the problem of mammalian epimorphic regeneration. Following casting of old hard antlers, new antlers regenerate from permanent bony protuberances, known as pedicles. Studies through morphological and histological examinations, tissue deletion and transplantation, and cellular and molecular techniques have demonstrated that antler renewal is markedly different from that of amphibian limb regeneration (dedifferentiation-based), being a stem cell-based epimorphic process. Antler stem cells reside in the pedicle periosteum. We envisage that epimorphic regeneration of mammalian appendages, other than antler, could be made possible by recreating comparable milieu to that which supports the elaboration of that structure from the pedicle periosteum. PMID:19492976

  4. Mammalian Fetal Cardiac Regeneration Following Myocardial Infarction is Associated with Differential Gene Expression Compared to the Adult

    PubMed Central

    Zgheib, Carlos; Allukian, Myron W.; Xu, Junwang; Morris, Michael W.; Caskey, Robert C.; Herdrich, Benjamin J.; Hu, Junyi; Gorman, Joseph H.; Gorman, Robert C.; Liechty, Kenneth W.

    2014-01-01

    Background In adults, MI results in a brisk inflammatory response, myocardium loss and scar formation. We have recently reported the first mammalian large animal model of cardiac regeneration following MI in fetal sheep. We hypothesize that the fetus ability to regenerate functional myocardium following MI is due to differential gene expression regulating the response to MI in the fetus compared to the adult. Methods MI was created in adult (n=4) or early gestation fetal (n=4) sheep. Tissue harvested after 3 or 30 days, RNA extracted for microarray, followed by PCA and global gene expression analysis for the gene ontology (GO) terms: “response to wounding”, “inflammatory response”, “extracellular matrix”, “cell cycle”, “cell migration”, “cell proliferation” and “apoptosis”. Results PCA demonstrated that the global gene expression pattern in adult infarcts was distinctly different from uninfarcted region at 3 days and remained different 30 days post-MI. In contrast, gene expression in the fetal infarct was different from the uninfarcted region at 3 days, but by 30 days it returned to a baseline expression pattern similar to the uninfarcted region. 3 days post-MI there was an increase in the expression of genes related to all GO terms in fetal and adult infarcts, but this increase was much more pronounced in adults. By 30 days, the fetal gene expression returned to baseline, whereas in the adult remained significantly elevated. Conclusions These data demonstrate that the global gene expression pattern is dramatically different in the fetal regenerative response to MI compared to the adult response and may partly be responsible for the regeneration. PMID:24792251

  5. A compact light-sheet microscope for the study of the mammalian central nervous system

    PubMed Central

    Yang, Zhengyi; Haslehurst, Peter; Scott, Suzanne; Emptage, Nigel; Dholakia, Kishan

    2016-01-01

    Investigation of the transient processes integral to neuronal function demands rapid and high-resolution imaging techniques over a large field of view, which cannot be achieved with conventional scanning microscopes. Here we describe a compact light sheet fluorescence microscope, featuring a 45° inverted geometry and an integrated photolysis laser, that is optimized for applications in neuroscience, in particular fast imaging of sub-neuronal structures in mammalian brain slices. We demonstrate the utility of this design for three-dimensional morphological reconstruction, activation of a single synapse with localized photolysis, and fast imaging of neuronal Ca2+ signalling across a large field of view. The developed system opens up a host of novel applications for the neuroscience community. PMID:27215692

  6. A compact light-sheet microscope for the study of the mammalian central nervous system

    NASA Astrophysics Data System (ADS)

    Yang, Zhengyi; Haslehurst, Peter; Scott, Suzanne; Emptage, Nigel; Dholakia, Kishan

    2016-05-01

    Investigation of the transient processes integral to neuronal function demands rapid and high-resolution imaging techniques over a large field of view, which cannot be achieved with conventional scanning microscopes. Here we describe a compact light sheet fluorescence microscope, featuring a 45° inverted geometry and an integrated photolysis laser, that is optimized for applications in neuroscience, in particular fast imaging of sub-neuronal structures in mammalian brain slices. We demonstrate the utility of this design for three-dimensional morphological reconstruction, activation of a single synapse with localized photolysis, and fast imaging of neuronal Ca2+ signalling across a large field of view. The developed system opens up a host of novel applications for the neuroscience community.

  7. A compact light-sheet microscope for the study of the mammalian central nervous system.

    PubMed

    Yang, Zhengyi; Haslehurst, Peter; Scott, Suzanne; Emptage, Nigel; Dholakia, Kishan

    2016-01-01

    Investigation of the transient processes integral to neuronal function demands rapid and high-resolution imaging techniques over a large field of view, which cannot be achieved with conventional scanning microscopes. Here we describe a compact light sheet fluorescence microscope, featuring a 45° inverted geometry and an integrated photolysis laser, that is optimized for applications in neuroscience, in particular fast imaging of sub-neuronal structures in mammalian brain slices. We demonstrate the utility of this design for three-dimensional morphological reconstruction, activation of a single synapse with localized photolysis, and fast imaging of neuronal Ca(2+) signalling across a large field of view. The developed system opens up a host of novel applications for the neuroscience community. PMID:27215692

  8. The mammalian tachykinin ligand-receptor system: an emerging target for central neurological disorders

    PubMed Central

    Pantaleo, Nick; Chadwick, Wayne; Park, Sung-Soo; Wang, Liyun; Zhou, Yu; Martin, Bronwen; Maudsley, Stuart

    2010-01-01

    Our understanding of the complex signaling neurophysiology of the central nervous system has facilitated the exploration of potential novel receptor-ligand system targets for disorders of this most complex organ. In recent years, many relatively neglected receptor-ligand systems have been re-evaluated with respect to their ability to potently modulate discrete tracts in the central nervous system. One such system is the tachykinin (previously neurokinin) system. The multiple heptahelical G protein-coupled receptors and neuropeptide ligands that comprise this system may be significantly involved in more central nervous systems actions than previously thought, including sleep disorders, amyotrophic lateral sclerosis, Alzheimer’s and Machado-Joseph disease. The development of our understanding of the role of the tachykinin receptor-ligand system in higher order central functions is likely to allow the creation of more specific and selective tachykinin-related neurotherapeutics. PMID:20632965

  9. Mammalian Axoneme Central Pair Complex Proteins: Broader Roles Revealed by Gene Knockout Phenotypes

    PubMed Central

    Teves, Maria E.; Nagarkatti-Gude, David R.; Zhang, Zhibing; Strauss, Jerome F.

    2016-01-01

    The axoneme genes, their encoded proteins, their functions and the structures they form are largely conserved across species. Much of our knowledge of the function and structure of axoneme proteins in cilia and flagella is derived from studies on model organisms like the green algae, Chlamydomonas reinhardtii. The core structure of cilia and flagella is the axoneme, which in most motile cilia and flagella contains a 9 + 2 configuration of microtubules. The two central microtubules are the scaffold of the central pair complex (CPC). Mutations that disrupt CPC genes in Chlamydomonas and other model organisms result in defects in assembly, stability and function of the axoneme, leading to flagellar motility defects. However, targeted mutations generated in mice in the orthologous CPC genes have revealed significant differences in phenotypes of mutants compared to Chlamydomonas. Here we review observations that support the concept of cell-type specific roles for the CPC genes in mice, and an expanded repertoire of functions for the products of these genes in cilia, including non-motile cilia, and other microtubule-associated cellular functions. PMID:26785425

  10. Central nervous system vasculitis in adults and children.

    PubMed

    Twilt, Marinka; Benseler, Susanne M

    2016-01-01

    Primary angiitis of the central nervous system (PACNS) is an inflammatory brain disease targeting the cerebral blood vessels, leading to a wide spectrum of signs and symptoms, including neurologic deficits, cognitive dysfunction, and psychiatric symptoms. The inflammation could be reversible if diagnosed and treated early. The diagnosis requires the careful consideration and rapid evaluation of systemic underlying conditions and disease mimics. The differential diagnosis is distinctly different for angiography-positive and -negative PACNS subtypes and differs depending on age, so there is childhood PACNS or adult PACNS. Distinct disease subtypes have been described, with characteristic disease course, neuroimaging findings, and histopathologic features. Novel and traditional biomarkers, including von Willebrand factor antigen and cytokine levels, can help diagnose, and define subtype and disease activity. Treatment of PACNS should be tailored to the disease subtypes and clinical symptoms. Beyond immunosuppression it should include medications to control symptoms in order to support and enhance the child's or adult's ability to actively participate in rehabilitation. The mortality of PACNS has decreased; studies determining the morbidity and its determinants are urgently needed. PMID:27112683

  11. Amino acids as central synaptic transmitters or modulators in mammalian thermoregulation

    SciTech Connect

    Bligh, J.

    1981-11-01

    Of the amino acids that affect the activity of central neurons, aspartate and glutamate (which exert generally excitatory influences) and glycine, taurine, and ..gamma..-aminobutyric acid (GABA) (which generally exert inhibitory influences) are the strongest neurotransmitter candidates. As with other putative transmitter substances, their effects on body temperature when injected into the cerebral ventricles or the preoptic hypothalamus tend to vary within and between species. These effects are uninterpretable without accompanying information regarding effector activity changes and the influences of dose and ambient temperature. Observations necessary for analysis of apparent action have been made in studies of the effects of intracerebroventricular injections of these amino acids into sheep. Aspartate and glutamate have similar excitatory effects on the pathway from cold sensors, whereas taurine and GABA exert inhibitory influences on the neural pathways that activate both heat production and heat loss effectors. Glycine appears to be without effect.

  12. Mutations in mammalian tolloid-like 1 gene detected in adult patients with ASD

    PubMed Central

    Stańczak, Paweł; Witecka, Joanna; Szydło, Anna; Gutmajster, Ewa; Lisik, Małgorzata; Auguściak-Duma, Aleksandra; Tarnowski, Maciej; Czekaj, Tomasz; Czekaj, Hanna; Sieroń, Aleksander L

    2009-01-01

    Atrial septal defect (ASD) is an incomplete septation of atria in human heart causing circulatory problems. Its frequency is estimated at one per 10 000. Actions of numerous genes have been linked to heart development. However, no single gene defect causing ASD has yet been identified. Incomplete heart septation similar to ASD was reported in transgenic mice with both inactive alleles of gene encoding mammalian zinc metalloprotease a mammalian tolloid-like 1 (tll1). Here, we have screened 19 ASD patients and 15 healthy age-matched individuals for mutations in TLL1 gene. All 22 exons were analyzed exon by exon for heteroduplex formation. Subsequently, DNA fragments forming heteroduplexes were sequenced. In four nonrelated patients, three missense mutations in coding sequence, and one single base change in the 5′UTR have been detected. Two mutations (Met182Leu, and Ala238Val) were detected in ASD patients with the same clinical phenotype. As the second mutation locates immediately upstream of the catalytic zinc-binding signature, it might change the enzyme substrate specificity. The third change, Leu627Val in the CUB3 domain, has been found in an ASD patient with interatrial septum aneurysm in addition to ASD. The CUB3 domain is important for substrate-specific recognition. In the remaining 15 patients as well as in 15 reference samples numerous base substitutions, deletions, and insertions have been detected, but no mutations changing the coding sequence have been found. Lack of mutations in relation to ASD of these patients could possibly be because of genetic heterogeneity of the syndrome. PMID:18830233

  13. Evaluation of Central Auditory Discrimination Abilities in Older Adults

    PubMed Central

    Freigang, Claudia; Schmidt, Lucas; Wagner, Jan; Eckardt, Rahel; Steinhagen-Thiessen, Elisabeth; Ernst, Arne; Rübsamen, Rudolf

    2011-01-01

    The present study focuses on auditory discrimination abilities in older adults aged 65–89 years. We applied the “Leipzig inventory for patient psychoacoustic” (LIPP), a psychoacoustic test battery specifically designed to identify deficits in central auditory processing. These tests quantify the just noticeable differences (JND) for the three basic acoustic parameters (i.e., frequency, intensity, and signal duration). Three different test modes [monaural, dichotic signal/noise (s/n) and interaural] were used, stimulus level was 35 dB sensation level. The tests are designed as three-alternative forced-choice procedure with a maximum-likelihood procedure estimating p = 0.5 correct response value. These procedures have proven to be highly efficient and provide a reliable outcome. The measurements yielded significant age-dependent deteriorations in the ability to discriminate single acoustic features pointing to progressive impairments in central auditory processing. The degree of deterioration was correlated to the different acoustic features and to the test modes. Most prominent, interaural frequency and signal duration discrimination at low test frequencies was elevated which indicates a deterioration of time- and phase-dependent processing at brain stem and cortical levels. LIPP proves to be an effective tool to identify basic pathophysiological mechanisms and the source of a specific impairment in auditory processing of the elderly. PMID:21577251

  14. A simple assessment model to quantifying the dynamic hippocampal neurogenic process in the adult mammalian brain.

    PubMed

    Choi, Minee L; Begeti, Faye; Barker, Roger A; Kim, Namho

    2016-04-01

    Adult hippocampal neurogenesis is a highly dynamic process in which new cells are born, but only some of which survive. Of late it has become clear that these surviving newborn neurons have functional roles, most notably in certain forms of memory. Conventional methods to look at adult neurogenesis are based on the quantification of the number of newly born neurons using a simple cell counting methodology. However, this type of approach fails to capture the dynamic aspects of the neurogenic process, where neural proliferation, death and differentiation take place continuously and simultaneously. In this paper, we propose a simple mathematical approach to better understand the adult neurogenic process in the hippocampus which in turn will allow for a better analysis of this process in disease states and following drug therapies. © 2015 Wiley Periodicals, Inc. PMID:26443687

  15. NMR imaging and spectroscopy of the mammalian central nervous system after heavy ion radiation

    SciTech Connect

    Richards, T.

    1984-09-01

    NMR imaging, NMR spectroscopic, and histopathologic techniques were used to study the proton relaxation time and related biochemical changes in the central nervous system after helium beam in vivo irradiation of the rodent brain. The spectroscopic observations reported in this dissertation were made possible by development of methods for measuring the NMR parameters of the rodent brain in vivo and in vitro. The methods include (1) depth selective spectroscopy using an optimization of rf pulse energy based on a priori knowledge of N-acetyl aspartate and lipid spectra of the normal brain, (2) phase-encoded proton spectroscopy of the living rodent using a surface coil, and (3) dual aqueous and organic tissue extraction technique for spectroscopy. Radiation induced increases were observed in lipid and p-choline peaks of the proton spectrum, in vivo. Proton NMR spectroscopy measurements on brain extracts (aqueous and organic solvents) were made to observe chemical changes that could not be seen in vivo. Radiation-induced changes were observed in lactate, GABA, glutamate, and p-choline peak areas of the aqueous fraction spectra. In the organic fraction, decreases were observed in peak area ratios of the terminal-methyl peaks, the N-methyl groups of choline, and at a peak at 2.84 ppM (phosphatidyl ethanolamine and phosphatidyl serine resonances) relative to TMS. With histology and Evans blue injections, blood-brain barrier alternations were seen as early as 4 days after irradiation. 83 references, 53 figures.

  16. Novel Action of FSH on Stem Cells in Adult Mammalian Ovary Induces Postnatal Oogenesis and Primordial Follicle Assembly.

    PubMed

    Bhartiya, Deepa; Parte, Seema; Patel, Hiren; Sriraman, Kalpana; Zaveri, Kusum; Hinduja, Indira

    2016-01-01

    Adult mammalian ovary has been under the scanner for more than a decade now since it was proposed to harbor stem cells that undergo postnatal oogenesis during reproductive period like spermatogenesis in testis. Stem cells are located in the ovary surface epithelium and exist in adult and menopausal ovary as well as in ovary with premature failure. Stem cells comprise two distinct populations including spherical, very small embryonic-like stem cells (VSELs which express nuclear OCT-4 and other pluripotent and primordial germ cells specific markers) and slightly bigger ovarian germ stem cells (OGSCs with cytoplasmic OCT-4 which are equivalent to spermatogonial stem cells in the testes). These stem cells have the ability to spontaneously differentiate into oocyte-like structures in vitro and on exposure to a younger healthy niche. Bone marrow may be an alternative source of these stem cells. The stem cells express FSHR and respond to FSH by undergoing self-renewal, clonal expansion, and initiating neo-oogenesis and primordial follicle assembly. VSELs are relatively quiescent and were recently reported to survive chemotherapy and initiate oogenesis in mice when exposed to FSH. This emerging understanding and further research in the field will help evolving novel strategies to manage ovarian pathologies and also towards oncofertility. PMID:26635884

  17. Novel Action of FSH on Stem Cells in Adult Mammalian Ovary Induces Postnatal Oogenesis and Primordial Follicle Assembly

    PubMed Central

    Bhartiya, Deepa; Parte, Seema; Patel, Hiren; Sriraman, Kalpana; Zaveri, Kusum; Hinduja, Indira

    2016-01-01

    Adult mammalian ovary has been under the scanner for more than a decade now since it was proposed to harbor stem cells that undergo postnatal oogenesis during reproductive period like spermatogenesis in testis. Stem cells are located in the ovary surface epithelium and exist in adult and menopausal ovary as well as in ovary with premature failure. Stem cells comprise two distinct populations including spherical, very small embryonic-like stem cells (VSELs which express nuclear OCT-4 and other pluripotent and primordial germ cells specific markers) and slightly bigger ovarian germ stem cells (OGSCs with cytoplasmic OCT-4 which are equivalent to spermatogonial stem cells in the testes). These stem cells have the ability to spontaneously differentiate into oocyte-like structures in vitro and on exposure to a younger healthy niche. Bone marrow may be an alternative source of these stem cells. The stem cells express FSHR and respond to FSH by undergoing self-renewal, clonal expansion, and initiating neo-oogenesis and primordial follicle assembly. VSELs are relatively quiescent and were recently reported to survive chemotherapy and initiate oogenesis in mice when exposed to FSH. This emerging understanding and further research in the field will help evolving novel strategies to manage ovarian pathologies and also towards oncofertility. PMID:26635884

  18. Adult mammalian stem cells: the role of Wnt, Lgr5 and R-spondins.

    PubMed

    Schuijers, Jurian; Clevers, Hans

    2012-06-13

    After its discovery as oncogen and morphogen, studies on Wnt focused initially on its role in animal development. With the finding that the colorectal tumour suppressor gene APC is a negative regulator of the Wnt pathway in (colorectal) cancer, attention gradually shifted to the study of the role of Wnt signalling in the adult. The first indication that adult Wnt signalling controls stem cells came from a Tcf4 knockout experiment: mutant mice failed to build crypt stem cell compartments. This observation was followed by similar findings in multiple other tissues. Recent studies have indicated that Wnt agonists of the R-spondin family provide potent growth stimuli for crypts in vivo and in vitro. Independently, Lgr5 was found as an exquisite marker for these crypt stem cells. The story has come full circle with the finding that the stem cell marker Lgr5 constitutes the receptor for R-spondins and occurs in complex with Frizzled/Lrp. PMID:22617424

  19. The herb community of a tropical forest in central Panamá: dynamics and impact of mammalian herbivores.

    PubMed

    Royo, Alejandro A; Carson, Walter P

    2005-08-01

    Mammals are hypothesized to either promote plant diversity by preventing competitive exclusion or limit diversity by reducing the abundance of sensitive plant species through their activities as browsers or disturbance agents. Previous studies of herbivore impacts in plant communities have focused on tree species and ignored the herbaceous community. In an experiment in mature-phase, tropical moist forest sites in central Panamá, we studied the impact of excluding ground-dwelling mammals on the richness and abundance of herbs in 16, 30x45-m plots. Within each plot, we censused the herbaceous community in 28, 2x2-m subplots (1,792 m2 total area sampled). We identified over 54 species of herbs averaging 1.21 ramets m-2 and covering approximately 4.25% of the forest floor. Excluding mammals for 5 years had no impact on overall species richness. Within exclosures, however, there was a significant two-fold increase in the density of rare species. Overall herbaceous density and percent cover did not differ between exclosures and adjacent control plots, although cover did increase over time. Mammalian exclusion significantly increased the total cover of three-dominant herb species, Pharus latifolius, Calathea inocephala, and Adiantum lucidum, but did not affect their density. This study represents one of the most extensive herbaceous community censuses conducted in tropical forests and is among a few that quantify herbaceous distribution and abundance in terms of both density and cover. Additionally, this work represents the first community level test of mammalian impacts on the herbaceous community in a tropical forest to date. Our results suggest that ground dwelling mammals do not play a key role in altering the relative abundance patterns of tropical herbs in the short term. Furthermore, our results contrast sharply with prior studies on similar temporal and spatial scales that demonstrate mammals strongly alter tree seedling composition and reduce seedling density

  20. Residential Pesticide Usage in Older Adults Residing in Central California

    PubMed Central

    Armes, Mary N.; Liew, Zeyan; Wang, Anthony; Wu, Xiangmei; Bennett, Deborah H.; Hertz-Picciotto, Irva; Ritz, Beate

    2011-01-01

    Information on residential pesticide usage and behaviors that may influence pesticide exposure was collected in three population-based studies of older adults residing in the three Central California counties of Fresno, Kern, and Tulare. We present data from participants in the Study of Use of Products and Exposure Related Behaviors (SUPERB) study (N = 153) and from community controls ascertained in two Parkinson’s disease studies, the Parkinson’s Environment and Gene (PEG) study (N = 359) and The Center for Gene-Environment Studies in Parkinson’s Disease (CGEP; N = 297). All participants were interviewed by telephone to obtain information on recent and lifetime indoor and outdoor residential pesticide use. Interviews ascertained type of product used, frequency of use, and behaviors that may influence exposure to pesticides during and after application. Well over half of all participants reported ever using indoor and outdoor pesticides; yet frequency of pesticide use was relatively low, and appeared to increase slightly with age. Few participants engaged in behaviors to protect themselves or family members and limit exposure to pesticides during and after treatment, such as ventilating and cleaning treated areas, or using protective equipment during application. Our findings on frequency of use over lifetime and exposure related behaviors will inform future efforts to develop population pesticide exposure models and risk assessment. PMID:21909294

  1. Exploring the Altered Dynamics of Mammalian Central Carbon Metabolic Pathway in Cancer Cells: A Classical Control Theoretic Approach

    PubMed Central

    Paul, Debjyoti; Dasgupta, Abhijit; De, Rajat K.

    2015-01-01

    Background In contrast with normal cells, most of the cancer cells depend on aerobic glycolysis for energy production in the form of adenosine triphosphate (ATP) bypassing mitochondrial oxidative phosphorylation. Moreover, compared to normal cells, cancer cells exhibit higher consumption of glucose with higher production of lactate. Again, higher rate of glycolysis provides the necessary glycolytic intermediary precursors for DNA, protein and lipid synthesis to maintain high active proliferation of the tumor cells. In this scenario, classical control theory based approach may be useful to explore the altered dynamics of the cancer cells. Since the dynamics of the cancer cells is different from that of the normal cells, understanding their dynamics may lead to development of novel therapeutic strategies. Method We have developed a model based on the state space equations of classical control theory along with an order reduction technique to mimic the actual dynamic behavior of mammalian central carbon metabolic (CCM) pathway in normal cells. Here, we have modified Michaelis Menten kinetic equation to incorporate feedback mechanism along with perturbations and cross talks associated with a metabolic pathway. Furthermore, we have perturbed the proposed model to reduce the mitochondrial oxidative phosphorylation. Thereafter, we have connected proportional-integral (PI) controller(s) with the model for tuning it to behave like the CCM pathway of a cancer cell. This methodology allows one to track the altered dynamics mediated by different enzymes. Results and Discussions The proposed model successfully mimics all the probable dynamics of the CCM pathway in normal cells. Moreover, experimental results demonstrate that in cancer cells, a coordination among enzymes catalyzing pentose phosphate pathway and intermediate glycolytic enzymes along with switching of pyruvate kinase (M2 isoform) plays an important role to maintain their altered dynamics. PMID:26367460

  2. Analogs of 2-amino-4-phosphonobutanoic acid (APB) as antagonists of excitatory neurotransmission in the mammalian central nervous system

    SciTech Connect

    Crooks, S.L.

    1986-01-01

    The status of L-glutamate as an excitatory neurotransmitter in the mammalian central nervous system awaits elucidation due to the lack of potent and specific antagonists. The glutamate analog L-2-amino-4-phosphonobutanoic acid (L-APB) is a moderately potent antagonist of excitatory neurotransmission in the rate hippocampus (IC/sub 50/) = 2.5 ..mu..M), and this compound invites development of potentially more potent analogs. The directions of exploration in this research include: (1) modification of the dianionic capability on the side chain of APB; (2) variation of the spatial relationships between the charged groups on APB; (3) substitution of methyl groups for hydrogens at the N-, 2-, 3-, and 4-positions of APB in order to probe the steric tolerance of the APB recognition site; and (4) restriction of the conformations available to APB by including its structure in cyclic analogs. The biological activity of the analogs was measured electrophysiologically in the rat hippocampal slice. The ability of the APB analogs to displace DL-(/sup 3/H)-APB from a rat brain synaptosomal membrane preparation was also measured. The dianionic capability of the phosphonate moiety was not crucial for antagonist activity but appeared to contribute greatly to potency. An ..cap alpha..-relationship of the amino group to the carboxylate moiety appeared to be crucial for activity. The cyclic analogs were weaker than APB, although cyclopentyl analogs of APB did retain useful activity. The differences in potency noted for the APB analogs in these two assays suggested that the APB recognition sites in these two systems were not identical.

  3. Long-Term, Stable Differentiation Of Human Embryonic Stem Cell-Derived Neural Precursors Grafted Into The Adult Mammalian Neostriatum

    PubMed Central

    Nasonkin, I.; Mahairaki, V.; Xu, L.; Hatfield, G.; Cummings, B.J.; Eberhart, C.; Ryugo, D.; Maric, D.; Bar, E.; Koliatsos, V.E.

    2010-01-01

    Stem-cell grafts have been advocated as experimental treatments for neurological diseases by virtue of their ability to offer trophic support for injured neurons and, theoretically, to replace dead neurons. Human embryonic stem cells (HESCs) are a rich source of neural precursors (NPs) for grafting, but have been questioned for their tendency to form tumors. Here we studied the ability of HESC-derived NP grafts optimized for cell number and differentiation stage prior to transplantation, to survive and stably differentiate and integrate in the basal forebrain (neostriatum) of young adult nude rats over long periods of time (6 months). NPs were derived from adherent monolayer cultures of HESCs exposed to noggin. After transplantation, NPs showed a drastic reduction in mitotic activity and an avid differentiation into neurons that projected via major white matter tracts to a variety of forebrain targets. A third of NP-derived neurons expressed the basal forebrain-neostriatal marker Dopamine- and cyclic AMP-Regulated Phosphoprotein. Graft-derived neurons formed mature synapses with host post-synaptic structures, including dendrite shafts and spines. NPs inoculated in white matter tracts showed a tendency towards glial (primarily astrocytic) differentiation, whereas NPs inoculated in the ventricular epithelium persisted as nestin (+) precursors. Our findings demonstrate the long-term ability of noggin-derived human NPs to structurally integrate tumor-free into the mature mammalian forebrain, while maintaining some cell fate plasticity that is strongly influenced by particular CNS niches. PMID:19609935

  4. Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain

    PubMed Central

    Guo, Junjie U.; Su, Yijing; Shin, Joo Heon; Shin, Jaehoon; Li, Hongda; Xie, Bin; Zhong, Chun; Hu, Shaohui; Le, Thuc; Fan, Guoping; Zhu, Heng; Chang, Qiang; Gao, Yuan; Ming, Guo-li; Song, Hongjun

    2014-01-01

    DNA methylation plays critical roles in the nervous system and has been traditionally considered to be restricted to CpG dinucleotides in metazoan genomes. Here we show that the single-base resolution DNA methylome from adult mouse dentate neurons consists of both CpG (~75%) and CpH (~25%) methylation (H = A/C/T). Neuronal CpH methylation is conserved in human brains, enriched in low CpG-density regions, depleted at protein-DNA interaction sites, and anti-correlated with gene expression. Functionally, both mCpGs and mCpHs can repress transcription in vitro and are recognized by MeCP2 in neurons in vivo. Unlike most CpG methylation, CpH methylation is established de novo during neuronal maturation and requires DNMT3A for active maintenance in post-mitotic neurons. These characteristics of CpH methylation suggest a significantly expanded proportion of the neuronal genome under cytosine methylation regulation and provide a new foundation for understanding the role of this key epigenetic modification in the nervous system. PMID:24362762

  5. Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System

    PubMed Central

    Baer, Matthew L.; Henderson, Scott C.; Colello, Raymond J.

    2015-01-01

    Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50–100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair. PMID:26562295

  6. Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System.

    PubMed

    Baer, Matthew L; Henderson, Scott C; Colello, Raymond J

    2015-01-01

    Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50-100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair. PMID:26562295

  7. Southern Hemisphere humpback whales wintering off Central America: insights from water temperature into the longest mammalian migration.

    PubMed

    Rasmussen, Kristin; Palacios, Daniel M; Calambokidis, John; Saborío, Marco T; Dalla Rosa, Luciano; Secchi, Eduardo R; Steiger, Gretchen H; Allen, Judith M; Stone, Gregory S

    2007-06-22

    We report on a wintering area off the Pacific coast of Central America for humpback whales (Megaptera novaeangliae) migrating from feeding areas off Antarctica. We document seven individuals, including a mother/calf pair, that made this migration (approx. 8300km), the longest movement undertaken by any mammal. Whales were observed as far north as 11 degrees N off Costa Rica, in an area also used by a boreal population during the opposite winter season, resulting in unique spatial overlap between Northern and Southern Hemisphere populations. The occurrence of such a northerly wintering area is coincident with the development of an equatorial tongue of cold water in the eastern South Pacific, a pattern that is repeated in the eastern South Atlantic. A survey of location and water temperature at the wintering areas worldwide indicates that they are found in warm waters (21.1-28.3 degrees C), irrespective of latitude. We contend that while availability of suitable reproductive habitat in the wintering areas is important at the fine scale, water temperature influences whale distribution at the basin scale. Calf development in warm water may lead to larger adult size and increased reproductive success, a strategy that supports the energy conservation hypothesis as a reason for migration. PMID:17412669

  8. Theory of Mind and Central Coherence in Adults with High-Functioning Autism or Asperger Syndrome

    ERIC Educational Resources Information Center

    Beaumont, Renae; Newcombe, Peter

    2006-01-01

    The study investigated theory of mind and central coherence abilities in adults with high-functioning autism (HFA) or Asperger syndrome (AS) using naturalistic tasks. Twenty adults with HFA/AS correctly answered significantly fewer theory of mind questions than 20 controls on a forced-choice response task. On a narrative task, there were no…

  9. Axonal Elongation into Peripheral Nervous System ``Bridges'' after Central Nervous System Injury in Adult Rats

    NASA Astrophysics Data System (ADS)

    David, Samuel; Aguayo, Albert J.

    1981-11-01

    The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model. When peripheral nerve segments were used as ``bridges'' between the medulla and spinal cord, axons from neurons at both these levels grew approximately 30 millimeters. The regenerative potential of these central neurons seems to be expressed when the central nervous system glial environment is changed to that of the peripheral nervous system.

  10. Comparison of ultrasonography-guided central venous catheterization between adult and pediatric populations.

    PubMed

    Tercan, Fahri; Oguzkurt, Levent; Ozkan, Ugur; Eker, Hatice Evren

    2008-01-01

    The purpose of this study was to compare the technical success and complication rates of ultrasonography-guided central venous catheterization between adult and pediatric patients which have not been reported previously. In a 4-year period, 859 ultrasonography-guided central vein catheterizations in 688 adult patients and 247 catheterizations in 156 pediatric patients were retrospectively evaluated. Mean age was 56.3 years (range, 18 to 95 years) for adults and 3.3 years (range, 0.1 to 16.3 years) for children. The preferred catheterization site was internal jugular vein in 97% of adults and 85% of children. The technical success rate, mean number of punctures, and rate of single wall puncture were 99.4%, 1.04 (range, 1-3), and 83% for adults and 90.3%, 1.25 (range, 1-5), and 49% for children, respectively. All the differences were statistically significant (p < 0.05). Complication rates were 2.3% and 2.4% for adults and children, respectively (p > 0.05). Major complications such as pneumothorax and hemothorax were not seen in any group. In conclusion, ultrasonography-guided central venous catheterization has a high technical success rate, lower puncture attempt rate, and higher single wall puncture rate in adults compared to children. Complication rates are comparable in the two groups. PMID:18330631

  11. Comparison of Ultrasonography-Guided Central Venous Catheterization Between Adult and Pediatric Populations

    SciTech Connect

    Tercan, Fahri Oguzkurt, Levent; Ozkan, Ugur; Eker, Hatice Evren

    2008-05-15

    The purpose of this study was to compare the technical success and complication rates of ultrasonography-guided central venous catheterization between adult and pediatric patients which have not been reported previously. In a 4-year period, 859 ultrasonography-guided central vein catheterizations in 688 adult patients and 247 catheterizations in 156 pediatric patients were retrospectively evaluated. Mean age was 56.3 years (range, 18 to 95 years) for adults and 3.3 years (range, 0.1 to 16.3 years) for children. The preferred catheterization site was internal jugular vein in 97% of adults and 85% of children. The technical success rate, mean number of punctures, and rate of single wall puncture were 99.4%, 1.04 (range, 1-3), and 83% for adults and 90.3%, 1.25 (range, 1-5), and 49% for children, respectively. All the differences were statistically significant (p < 0.05). Complication rates were 2.3% and 2.4% for adults and children, respectively (p > 0.05). Major complications such as pneumothorax and hemothorax were not seen in any group. In conclusion, ultrasonography-guided central venous catheterization has a high technical success rate, lower puncture attempt rate, and higher single wall puncture rate in adults compared to children. Complication rates are comparable in the two groups.

  12. Clonal development and organization of the adult Drosophila central brain

    PubMed Central

    Yu, Hung-Hsiang; Awasaki, Takeshi; Schroeder, Mark David; Long, Fuhui; Yang, Jacob S.; He, Yisheng; Ding, Peng; Kao, Jui-Chun; Wu, Gloria Yueh-Yi; Peng, Hanchuan; Myers, Gene; Lee, Tzumin

    2013-01-01

    Summary Background The insect brain can be divided into neuropils that are formed by neurites of both local and remote origin. The complexity of the interconnections obscures how these neuropils are established and interconnected through development. The Drosophila central brain develops from a fixed number of neuroblasts (NBs) that deposit neurons in regional clusters. Results By determining individual NB clones and pursuing their projections into specific neuropils we unravel the regional development of the brain neural network. Exhaustive clonal analysis revealed 95 stereotyped neuronal lineages with characteristic cell body locations and neurite trajectories. Most clones show complex projection patterns, but despite the complexity, neighboring clones often co-innervate the same local neuropil(s) and further target a restricted set of distant neuropils. Conclusions These observations argue for regional clonal development of both neuropils and neuropil connectivity throughout the Drosophila central brain. PMID:23541733

  13. Growth factor enhanced retroviral gene transfer to the adult central nervous system.

    PubMed

    King, L A; Mitrophanous, K A; Clark, L A; Kim, V N; Rohll, J B; Kingsman, A J; Colello, R J

    2000-07-01

    The use of viral vectors for gene delivery into mammalian cells provides a new approach in the treatment of many human diseases. The first viral vector approved for human clinical trials was murine leukemia virus (MLV), which remains the most commonly used vector in clinical trials to date. However, the application of MLV vectors is limited since MLV requires cells to be actively dividing in order for transduction and therefore gene delivery to occur. This limitation precludes the use of MLV for delivering genes to the adult CNS, where very little cell division is occurring. However, we speculated that this inherent limitation of ML V may be overcome by utilizing the known mitogenic effect of growth factors on cells of the CNS. Specifically, an in vivo application of growth factor to the adult brain, if able to induce cell division, could enhance MLV-based gene transfer to the adult brain. We now show that an exogenous application of basic fibroblast growth factor induces cell division in vivo. Under these conditions, where cells of the adult brain are stimulated to divide, MLV-based gene transfer is significantly enhanced. This novel approach precludes any vector modifications and provides a simple and effective way of delivering genes to cells of the adult brain utilizing MLV-based retroviral vectors. PMID:10918476

  14. Mammalian sleep

    NASA Astrophysics Data System (ADS)

    Staunton, Hugh

    2005-05-01

    This review examines the biological background to the development of ideas on rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its relation to dreaming. Aspects of the phenomenon which are discussed include physiological changes and their anatomical location, the effects of total and selective sleep deprivation in the human and animal, and REM sleep behavior disorder, the latter with its clinical manifestations in the human. Although dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human, there is a contingent relation between REM sleep and dreaming. Thus, REM is taken as a marker for dreaming and as REM is distributed ubiquitously throughout the mammalian class, it is suggested that other mammals also dream. It is suggested that the overall function of REM sleep/dreaming is more important than the content of the individual dream; its function is to place the dreamer protagonist/observer on the topographical world. This has importance for the developing infant who needs to develop a sense of self and separateness from the world which it requires to navigate and from which it is separated for long periods in sleep. Dreaming may also serve to maintain a sense of ‘I’ness or “self” in the adult, in whom a fragility of this faculty is revealed in neurological disorders.

  15. College and Adult Reading XI: The Eleventh Yearbook of the North Central Reading Association.

    ERIC Educational Resources Information Center

    Fisher, Joseph A., Ed.

    This yearbook contains selected papers presented at the twenty-third and twenty-fourth annual meetings of the North Central Reading Association, held in October of 1981 and 1982. Papers in the yearbook include: "History of Adult Reading Programs" (Clarence Anderson); "About Creativity and Study Skills" (Mark E. Thompson); "Recent Changes in…

  16. Cellular and Molecular Characterization of Multipolar Map5-Expressing Cells: A Subset of Newly Generated, Stage-Specific Parenchymal Cells in the Mammalian Central Nervous System

    PubMed Central

    Crociara, Paola; Parolisi, Roberta; Conte, Daniele; Fumagalli, Marta; Bonfanti, Luca

    2013-01-01

    Although extremely interesting in adult neuro-glio-genesis and promising as an endogenous source for repair, parenchymal progenitors remain largely obscure in their identity and physiology, due to a scarce availability of stage-specific markers. What appears difficult is the distinction between real cell populations and various differentiation stages of the same population. Here we focused on a subset of multipolar, polydendrocyte-like cells (mMap5 cells) expressing the microtubule associated protein 5 (Map5), which is known to be present in most neurons. We characterized the morphology, phenotype, regional distribution, proliferative dynamics, and stage-specific marker expression of these cells in the rabbit and mouse CNS, also assessing their existence in other mammalian species. mMap5 cells were never found to co-express the Ng2 antigen. They appear to be a population of glial cells sharing features but also differences with Ng2+progenitor cells. We show that mMap5 cells are newly generated, postmitotic parenchymal elements of the oligodendroglial lineage, thus being a stage-specific population of polydendrocytes. Finally, we report that the number of mMap5 cells, although reduced within the brain of adult/old animals, can increase in neurodegenerative and traumatic conditions. PMID:23667595

  17. Next generation of non-mammalian blood-brain barrier models to study parasitic infections of the central nervous system

    PubMed Central

    Siddiqui, Ruqaiyyah; Edwards-Smallbone, James; Flynn, Robin; Khan, Naveed Ahmed

    2012-01-01

    Transmigration of neuropathogens across the blood-brain barrier is a key step in the development of central nervous system infections, making it a prime target for drug development. The ability of neuropathogens to traverse the blood-brain barrier continues to inspire researchers to understand the specific strategies and molecular mechanisms that allow them to enter the brain. The availability of models of the blood-brain barrier that closely mimic the situation in vivo offers unprecedented opportunities for the development of novel therapeutics. PMID:21921682

  18. National Economic Development Status May Affect the Association between Central Adiposity and Cognition in Older Adults

    PubMed Central

    Maharani, Asri; Tampubolon, Gindo

    2016-01-01

    Background Obesity is becoming a global problem, rather than one found only in developed countries. Although recent studies have suggested a detrimental effect of obesity on cognition, studies of the relationship between obesity and cognition among older adults have been limited to developed countries. We aimed to examine the associations between central obesity, as measured by waist circumference, and cognition level in adults aged 50 years and older in England and Indonesia. Methods We used linear regression models to analyse these associations and multiple imputation to manage missing data. The 2006 English Longitudinal Study of Ageing Wave 3 is the source of data from England, while data from Indonesia is sourced from the 2007 Indonesian Family Life Survey Wave 4. Findings Centrally obese respondents had lower cognition levels than non-centrally obese respondents in England. In contrast, central adiposity had a statistically significant positive association with cognition in Indonesia. Higher levels of education and higher economic status were associated with higher cognitive ability, while age was associated with lower cognition in both countries. Elevated C-reactive protein (CRP) concentrations and smoking behaviour, both linked to higher risk of obesity, were negatively associated with cognitive ability among older adults in England, but they had no statistically significant association with cognition among Indonesians. Interpretation The contradictory findings on obesity and cognition in England and Indonesia not only create a puzzle, but they may also have different policy implications in these countries. Reducing the prevalence of obesity may be the main focus in England and other developed countries to maintain older adults’ cognition. However, Indonesia and other developing countries should place more emphasis on education, in addition to continued efforts to tackle the double burden of malnutrition, in order to prevent cognitive impairment among

  19. Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system.

    PubMed

    Marques, Sueli; Zeisel, Amit; Codeluppi, Simone; van Bruggen, David; Mendanha Falcão, Ana; Xiao, Lin; Li, Huiliang; Häring, Martin; Hochgerner, Hannah; Romanov, Roman A; Gyllborg, Daniel; Muñoz-Manchado, Ana B; La Manno, Gioele; Lönnerberg, Peter; Floriddia, Elisa M; Rezayee, Fatemah; Ernfors, Patrik; Arenas, Ernest; Hjerling-Leffler, Jens; Harkany, Tibor; Richardson, William D; Linnarsson, Sten; Castelo-Branco, Gonçalo

    2016-06-10

    Oligodendrocytes have been considered as a functionally homogeneous population in the central nervous system (CNS). We performed single-cell RNA sequencing on 5072 cells of the oligodendrocyte lineage from 10 regions of the mouse juvenile and adult CNS. Thirteen distinct populations were identified, 12 of which represent a continuum from Pdgfra(+) oligodendrocyte precursor cells (OPCs) to distinct mature oligodendrocytes. Initial stages of differentiation were similar across the juvenile CNS, whereas subsets of mature oligodendrocytes were enriched in specific regions in the adult brain. Newly formed oligodendrocytes were detected in the adult CNS and were responsive to complex motor learning. A second Pdgfra(+) population, distinct from OPCs, was found along vessels. Our study reveals the dynamics of oligodendrocyte differentiation and maturation, uncoupling them at a transcriptional level and highlighting oligodendrocyte heterogeneity in the CNS. PMID:27284195

  20. Using DNA barcoding to link cystacanths and adults of the acanthocephalan Polymorphus brevis in central Mexico.

    PubMed

    Alcántar-Escalera, F J; García-Varela, M; Vázquez-Domínguez, E; Pérez-Ponce de León, G

    2013-11-01

    In parasitic organisms, particularly helminths, the usage of the mitochondrial cytochrome c oxidase subunit I gene as the standard DNA barcoding region for species identification and discovery has been very limited. Here, we present an integrated study, based on both DNA barcoding and morphological analyses, for acanthocephalans belonging to the genus Polymorphus, whose larvae (cystacanths) are commonly found in the mesentery of freshwater fishes, while adults are found in the intestine of fish-eating birds. The alpha taxonomy of parasitic helminths is based on adult morphological traits, and because of that larval forms cannot be identified to species level based on morphology alone. DNA barcoding offers an alternative tool for linking larval stages of parasitic organisms to known adults. We sequenced cystacanths collected from freshwater fishes in localities across central Mexico and adults obtained from fish-eating birds, to determine whether they were conspecific. To corroborate the molecular results, we conducted a morphometric analysis with 'Proboscis profiler', which is a software tool developed to detect heterogeneity in morphologically similar acanthocephalans based on the multivariate statistical analysis of proboscis hook dimensions. Both sources of information indicate that cystacanths infecting freshwater fishes in central Mexico belong to a single species, Polymorphus brevis. PMID:23480472

  1. Non-human primate fetal kidney transcriptome analysis indicates mammalian target of rapamycin (mTOR) is a central nutrient-responsive pathway

    PubMed Central

    Nijland, Mark J; Schlabritz-Loutsevitch, Natalia E; Hubbard, Gene B; Nathanielsz, Peter W; Cox, Laura A

    2007-01-01

    Developmental programming is defined as the process by which gene–environment interaction in the developing organism leads to permanent changes in phenotype and function. Numerous reports of maternal nutrient restriction during pregnancy demonstrate altered renal development. Typically this alteration manifests as a reduction in the total number of glomeruli in the mature kidney of the offspring, and suggests that predisposition to develop chronic renal disease may include an in utero origin. In a previous study, we defined the transcriptome in the kidney from fetuses of control (CON, fed ad libitum) and nutrient-restricted (NR, fed 70% of CON starting at 0.16 gestation (G)) pregnancies at half-way through gestation (0.5G), and established transcriptome and morphological changes in NR kidneys compared to CON. One goal of the present study was to use transcriptome data from fetal kidneys of CON and NR mothers at 0.5G with histological data to identify the molecular mechanisms that may regulate renal development. A second goal was to identify mechanisms by which NR elicits its affect on fetal baboon kidney. We have used an end-of-pathway gene expression analysis to prioritize and identify key pathways regulating the 0.5G kidney phenotype in response NR. From these data we have determined that the mammalian target of rapamycin (mTOR) signalling pathway is central to this phenotype. PMID:17185341

  2. A fuzzy logic controller based approach to model the switching mechanism of the mammalian central carbon metabolic pathway in normal and cancer cells.

    PubMed

    Dasgupta, Abhijit; Paul, Debjyoti; De, Rajat K

    2016-07-19

    Dynamics of large nonlinear complex systems, like metabolic networks, depend on several parameters. A metabolic pathway may switch to another pathway in accordance with the current state of parameters in both normal and cancer cells. Here, most of the parameter values are unknown to us. A fuzzy logic controller (FLC) has been developed here for the purpose of modeling metabolic networks by approximating the reasons for the behaviour of a system and applying expert knowledge to track switching between metabolic pathways. The simulation results can track the switching between glycolysis and gluconeogenesis, as well as glycolysis and pentose phosphate pathways (PPP) in normal cells. Unlike normal cells, pyruvate kinase (M2 isoform) (PKM2) switches alternatively between its two oligomeric forms, i.e. an active tetramer and a relatively low activity dimer, in cancer cells. Besides, there is a coordination among PKM2 switching and enzymes catalyzing PPP. These phenomena help cancer cells to maintain their high energy demand and macromolecular synthesis. However, the reduction of initial adenosine triphosphate (ATP) to a very low concentration, decreasing initial glucose uptake, destroying coordination between glycolysis and PPP, and replacement of PKM2 by its relatively inactive oligomeric form (dimer) or inhibition of the translation of PKM2 may destabilize the mutated control mechanism of the mammalian central carbon metabolic (CCM) pathway in cancer cells. The performance of the model is compared appropriately with some existing ones. PMID:27225801

  3. Increasing trends in central obesity among Chinese adults with normal body mass index, 1993–2009

    PubMed Central

    2013-01-01

    Background Central obesity is thought to be more pathogenic than overall obesity and studies have shown that the association between waist circumference (WC) and mortality was strongest in those with a normal body mass index (BMI). The objective of our study was to determine secular trends in the prevalence of central obesity (WC ≥ 90 cm for men and ≥ 80 cm for women) among Chinese adults with normal BMI from 1993 to 2009 and to examine the impact of performance of combined BMI and WC on the prevalence of obesity in Chinese adults. Methods We used data from the China Health and Nutrition Survey (CHNS) conducted from 1993 to 2009. From which we included a total of 52023 participants aged ≥ 18 years. Results The age-standardized prevalence of central obesity among Chinese adults with BMI < 25 kg/m2 increased from 11.9% in 1993 to 21.1% in 2009 (P for linear trend <0.001). The upward trends were noted in both genders, all ages, rural/urban settings, and education groups (all P for linear trend <0.001), with greater increments in men, participants aged 18–64 years, and rural residents (P for interaction terms survey × sex, survey × age, and survey × rural/urban settings were 0.042, 0.003, and < 0.001, respectively). Trends in the prevalence of central obesity were similar when a more stringent BMI < 23 kg/m2 cut point (Asian cut point) was applied. Central obesity is associated with a higher risk of incident hypertension within normal BMI category. More than 65% individuals with obesity would be missed if solely BMI was measured. Conclusions We observed an upward trend in the prevalence of central obesity among participants with normal BMI irrespective of sex, age, rural/urban settings, and education level. Central obesity is associated with a higher risk of incident hypertension within normal BMI category. Approximately two thirds of the individuals with obesity would be missed if WC was not measured. It is, therefore, urgent to emphasize the importance of

  4. Adult multisystem langerhans cell histiocytosis presenting with central diabetes insipidus successfully treated with chemotherapy.

    PubMed

    Choi, Jung-Eun; Lee, Hae Ri; Ohn, Jung Hun; Moon, Min Kyong; Park, Juri; Lee, Seong Jin; Choi, Moon-Gi; Yoo, Hyung Joon; Kim, Jung Han; Hong, Eun-Gyoung

    2014-09-01

    We report the rare case of an adult who was diagnosed with recurrent multisystem Langerhans cell histiocytosis (LCH) involving the pituitary stalk and lung who present with central diabetes insipidus and was successfully treated with systemic steroids and chemotherapy. A 49-year-old man visited our hospital due to symptoms of polydipsia and polyuria that started 1 month prior. Two years prior to presentation, he underwent excision of right 6th and 7th rib lesions for the osteolytic lesion and chest pain, which were later confirmed to be LCH on pathology. After admission, the water deprivation test was done and the result indicated that he had central diabetes insipidus. Sella magnetic resonance imaging showed a mass on the pituitary stalk with loss of normal bright spot at the posterior lobe of the pituitary. Multiple patchy infiltrations were detected in both lung fields by computed tomography (CT). He was diagnosed with recurrent LCH and was subsequently treated with inhaled desmopressin, systemic steroids, vinblastine, and mercaptopurine. The pituitary mass disappeared after two months and both lungs were clear on chest CT after 11 months. Although clinical remission in multisystem LCH in adults is reportedly rare, our case of adult-onset multisystem LCH was treated successfully with systemic chemotherapy using prednisolone, vinblastine, and 6-mercaptopurine, which was well tolerated. PMID:25309800

  5. Adult Multisystem Langerhans Cell Histiocytosis Presenting with Central Diabetes Insipidus Successfully Treated with Chemotherapy

    PubMed Central

    Choi, Jung-Eun; Lee, Hae Ri; Ohn, Jung Hun; Moon, Min Kyong; Park, Juri; Lee, Seong Jin; Choi, Moon-Gi; Yoo, Hyung Joon; Kim, Jung Han

    2014-01-01

    We report the rare case of an adult who was diagnosed with recurrent multisystem Langerhans cell histiocytosis (LCH) involving the pituitary stalk and lung who present with central diabetes insipidus and was successfully treated with systemic steroids and chemotherapy. A 49-year-old man visited our hospital due to symptoms of polydipsia and polyuria that started 1 month prior. Two years prior to presentation, he underwent excision of right 6th and 7th rib lesions for the osteolytic lesion and chest pain, which were later confirmed to be LCH on pathology. After admission, the water deprivation test was done and the result indicated that he had central diabetes insipidus. Sella magnetic resonance imaging showed a mass on the pituitary stalk with loss of normal bright spot at the posterior lobe of the pituitary. Multiple patchy infiltrations were detected in both lung fields by computed tomography (CT). He was diagnosed with recurrent LCH and was subsequently treated with inhaled desmopressin, systemic steroids, vinblastine, and mercaptopurine. The pituitary mass disappeared after two months and both lungs were clear on chest CT after 11 months. Although clinical remission in multisystem LCH in adults is reportedly rare, our case of adult-onset multisystem LCH was treated successfully with systemic chemotherapy using prednisolone, vinblastine, and 6-mercaptopurine, which was well tolerated. PMID:25309800

  6. Muscle Strength, Physical Activity, and Functional Limitations in Older Adults with Central Obesity

    PubMed Central

    Germain, Cassandra M.; Batsis, John A.; Vasquez, Elizabeth; McQuoid, Douglas R.

    2016-01-01

    Background. Obesity and muscle weakness are independently associated with increased risk of physical and functional impairment in older adults. It is unknown whether physical activity (PA) and muscle strength combined provide added protection against functional impairment. This study examines the association between muscle strength, PA, and functional outcomes in older adults with central obesity. Methods. Prevalence and odds of physical (PL), ADL, and IADL limitation were calculated for 6,388 community dwelling adults aged ≥ 60 with central obesity. Individuals were stratified by sex-specific hand grip tertiles and PA. Logistic models were adjusted for age, education, comorbidities, and body-mass index and weighted. Results. Overall prevalence of PL and ADL and IADL limitations were progressively lower by grip category. Within grip categories, prevalence was lower for individuals who were active than those who were inactive. Adjusted models showed significantly lower odds of PL OR 0.42 [0.31, 0.56]; ADL OR 0.60 [0.43, 0.84], and IADL OR 0.46 [0.35, 0.61] for those in the highest grip strength category as compared to those in the lowest grip category. Conclusion. Improving grip strength in obese elders who are not able to engage in traditional exercise is important for reducing odds of physical and functional impairment. PMID:27034833

  7. Neonatal exposure to amphetamine alters social affiliation and central dopamine activity in adult male prairie voles.

    PubMed

    Fukushiro, D F; Olivera, A; Liu, Y; Wang, Z

    2015-10-29

    The prairie vole (Microtus ochrogaster) is a socially monogamous rodent species that forms pair bonds after mating. Recent data have shown that amphetamine (AMPH) is rewarding to prairie voles as it induces conditioned place preferences. Further, repeated treatment with AMPH impairs social bonding in adult prairie voles through a central dopamine (DA)-dependent mechanism. The present study examined the effects of neonatal exposure to AMPH on behavior and central DA activity in adult male prairie voles. Our data show that neonatal exposure to AMPH makes voles less social in an affiliation test during adulthood, but does not affect animals' locomotor activity and anxiety-like behavior. Neonatal exposure to AMPH also increases the levels of tyrosine hydroxylase (TH) and DA transporter (DAT) mRNA expression in the ventral tegmental area (VTA) in the brain, indicating an increase in central DA activity. As DA has been implicated in AMPH effects on behavioral and cognitive functions, altered DA activity in the vole brain may contribute to the observed changes in social behavior. PMID:26321240

  8. Prevalence of Central Obesity among Adults with Normal BMI and Its Association with Metabolic Diseases in Northeast China

    PubMed Central

    Zhang, Peng; Wang, Rui; Gao, Chunshi; Jiang, Lingling; Lv, Xin; Song, Yuanyuan; Li, Bo

    2016-01-01

    Objectives The present study aimed to investigate the prevalence of central obesity among adults with normal BMI and its association with metabolic diseases in Jilin Province, China. Methods A population-based cross-sectional study was conducted in 2012 in Jilin Province of China. Information was collected by face to face interview. Descriptive data analysis and 95% confidence intervals (CI) of prevalence/frequency were conducted. Log-binomial regression analyses were used to find the independent factors associated with central obesity and to explore the adjusted association between central obesity and metabolic diseases among adults with normal BMI. Results Among the adult residents with normal BMI in Jilin Province, 55.6% of participants with central obesity self-assessed as normal weight and 27.0% thought their body weight were above normal. 12.7% of central obesity people took methods to lose weight, while 85.3% didn’t. Female, older people and non-manual worker had higher risk to be central obesity among adults with normal BMI. Hypertension, diabetes and hyperlipidemia were significantly associated with central obesity among adults with normal BMI, the PRs were 1.337 (1.224–1.461), 1.323 (1.193–1.456) and 1.261 (1.152–1.381) separately when adjusted for gender, age and BMI. Conclusions Hypertension, diabetes and hyperlipidemia were significantly associated with central obesity among adults with normal BMI in Jilin Province, China. The low rates of awareness and control of central obesity among adults with normal BMI should be improved by government and health department. PMID:27467819

  9. In Vivo Neural Tissue Engineering: Cylindrical Biocompatible Hydrogels That Create New Neural Tracts in the Adult Mammalian Brain.

    PubMed

    Clark, Amanda R; Carter, Arrin B; Hager, Lydia E; Price, Elmer M

    2016-08-01

    Individuals with neurodegenerative disorders or brain injury have few treatment options and it has been proposed that endogenous adult neural stem cells can be harnessed to repopulate dysfunctional nonneurogenic regions of the brain. We have accomplished this through the development of rationally designed hydrogel implants that recruit endogenous cells from the adult subventricular zone to create new relatively long tracts of neuroblasts. These implants are biocompatible and biodegradable cylindrical hydrogels consisting of fibrin and immobilized neurotrophic factors. When implanted into rat brain such that the cylinder intersected the migratory path of endogenous neural progenitors (the rostral migratory stream) and led into the nonneurogenic striatum, we observed a robust neurogenic response in the form of migrating neuroblasts with long (>100 μm) complex neurites. The location of these new neural cells in the striatum was directly coincident with the original track of the fibrin implant, which itself had completely degraded, and covered a significant area and distance (>2.5 mm). We also observed a significant number of neuroblasts in the striatal region between the implant track and the lateral ventricle. When these fibrin cylinders were implanted into hemiparkinson rats, correction of parkinsonian behavior was observed. There were no obvious behavioral, inflammatory or tumorigenic sequelae as a consequence of the implants. In conclusion, we have successfully engineered neural tissue in vivo, using neurogenic biomaterials cast into a unique cylindrical architecture. These results represent a novel approach to efficiently induce neurogenesis in a controlled and targeted manner, which may lead toward a new therapeutic modality for neurological disorders. PMID:27295980

  10. Potential of adult mammalian lumbosacral spinal cord to execute and acquire improved locomotion in the absence of supraspinal input

    NASA Technical Reports Server (NTRS)

    Edgerton, V. R.; Roy, R. R.; Hodgson, J. A.; Prober, R. J.; de Guzman, C. P.; de Leon, R.

    1992-01-01

    The neural circuitry of the lumbar spinal cord can generate alternating extension and flexion of the hindlimbs. The hindlimbs of adult cats with complete transection of the spinal cord at a low thoracic level (T12-T13) can perform full weight-supporting locomotion on a treadmill belt moving at a range of speeds. Some limitations in the locomotor capacity can be associated with a deficit in the recruitment level of the fast extensors during the stance phase and the flexors during the swing phase of a step cycle. The level of locomotor performance, however, can be enhanced by daily training on a treadmill while emphasizing full weight-support stepping and by providing appropriately timed sensory stimulation, loading, and/or pharmacologic stimulation of the hindlimb neuromuscular apparatus. Furthermore, there appears to be an interactive effect of these interventions. For example, the maximum treadmill speed that a spinal adult cat can attain and maintain is significantly improved with daily full weight-supporting treadmill training, but progressive recruitment of fast extensors becomes apparent only when the hindlimbs are loaded by gently pulling down on the tail during the stepping. Stimulation of the sural nerve at the initiation of the flexion phase of the step cycle can likewise markedly improve the locomotor capability. Administration of clonidine, in particular in combination with an elevated load, resulted in the most distinct and consistent alternating bursts of electromyographic activity during spinal stepping. These data indicate that the spinal cord has the ability to execute alternating activation of the extensor and flexor musculature of the hindlimbs (stepping) and that this ability can be improved by several interventions such as training, sensory stimulation, and use of some pharmacologic agents. Thus, it appears that the spinal cord, without supraspinal input, is highly plastic and has the potential to "learn," that is, to acquire and improve its

  11. Comparing the Push-Pull Versus Discard Blood Sample Method From Adult Central Vascular Access Devices.

    PubMed

    Byrne, Dia

    2016-01-01

    This study demonstrates the feasibility of replacing the discard blood sampling method for central vascular access devices with the push-pull method. A comparative, within-subject design was used to evaluate 61 unique, paired blood samples from 1 adult outpatient oncology clinic. A 21-measure laboratory panel was conducted on each of the paired samples. Interpretation showed a small mean bias and excellent agreement between the methods. Blood samples obtained using the push-pull method were within clinically acceptable ranges. No hemolysis was noted by laboratory evaluation of 59 samples. PMID:27074989

  12. NF-KappaB in Long-Term Memory and Structural Plasticity in the Adult Mammalian Brain

    PubMed Central

    Kaltschmidt, Barbara; Kaltschmidt, Christian

    2015-01-01

    The transcription factor nuclear factor kappaB (NF-κB) is a well-known regulator of inflammation, stress, and immune responses as well as cell survival. In the nervous system, NF-κB is one of the crucial components in the molecular switch that converts short- to long-term memory—a process that requires de novo gene expression. Here, the researches published on NF-κB and downstream target genes in mammals will be reviewed, which are necessary for structural plasticity and long-term memory, both under normal and pathological conditions in the brain. Genetic evidence has revealed that NF-κB regulates neuroprotection, neuronal transmission, and long-term memory. In addition, after genetic ablation of all NF-κB subunits, a severe defect in hippocampal adult neurogenesis was observed during aging. Proliferation of neural precursors is increased; however, axon outgrowth, synaptogenesis, and tissue homeostasis of the dentate gyrus are hampered. In this process, the NF-κB target gene PKAcat and other downstream target genes such as Igf2 are critically involved. Therefore, NF-κB activity seems to be crucial in regulating structural plasticity and replenishment of granule cells within the hippocampus throughout the life. In addition to the function of NF-κB in neurons, we will discuss on a neuroinflammatory role of the transcription factor in glia. Finally, a model for NF-κB homeostasis on the molecular level is presented, in order to explain seemingly the contradictory, the friend or foe, role of NF-κB in the nervous system. PMID:26635522

  13. Acceptability of mobile health interventions to reduce inactivity-related health risk in central Pennsylvania adults

    PubMed Central

    Yang, Chih-Hsiang; Maher, Jaclyn P.; Conroy, David E.

    2015-01-01

    Insufficient physical activity and excessive sedentary behavior elevate health risk. Mobile applications (apps) provide one mode for delivering interventions to modify these behaviors and reduce health risk. The purpose of this study was to characterize the need for and acceptability of health behavior interventions among rural adults and evaluate the interest in and the value of app-based interventions in this population. Central Pennsylvania adults with smartphones (N = 258) completed a brief web survey in October–November 2012. Most adults report one or both inactivity-related behavioral risk factors, would use a free app to modify those risk behaviors, and would pay a small amount for that app. Low-cost, efficacious apps to increase physical activity or reduce sedentary behavior should be promoted in public health practice. User experience should be at the forefront of this process to increase value and minimize burden in the service of long-term engagement, behavior change, and health risk reduction. PMID:26844135

  14. Acceptability of mobile health interventions to reduce inactivity-related health risk in central Pennsylvania adults.

    PubMed

    Yang, Chih-Hsiang; Maher, Jaclyn P; Conroy, David E

    2015-01-01

    Insufficient physical activity and excessive sedentary behavior elevate health risk. Mobile applications (apps) provide one mode for delivering interventions to modify these behaviors and reduce health risk. The purpose of this study was to characterize the need for and acceptability of health behavior interventions among rural adults and evaluate the interest in and the value of app-based interventions in this population. Central Pennsylvania adults with smartphones (N = 258) completed a brief web survey in October-November 2012. Most adults report one or both inactivity-related behavioral risk factors, would use a free app to modify those risk behaviors, and would pay a small amount for that app. Low-cost, efficacious apps to increase physical activity or reduce sedentary behavior should be promoted in public health practice. User experience should be at the forefront of this process to increase value and minimize burden in the service of long-term engagement, behavior change, and health risk reduction. PMID:26844135

  15. Evaluation of neck circumference as a predictor of central obesity and insulin resistance in Chinese adults

    PubMed Central

    Wang, Xuhong; Zhang, Ning; Yu, Caiguo; Ji, Zhili

    2015-01-01

    Objectives: To evaluate whether neck circumference (NC) could be used as a valid and effective method for identifying obesity and insulin resistance (IR) in Chinese adults. Methods: A total of 3307 adults aged 20-65 years were randomly recruited from two communities of Tongzhou, Beijing. Height, weight, waist circumference (WC), hip circumference (HC), neck circumference (NC), blood pressure, fasting plasma glucose (FPG), fasting serum insulin (FINS), total cholesterol (TC), serum triglyceride (TG), High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and Urinary albumin (UAlb) were measured. Pearson correlation coefficient was used to explore the relationship between NC and other measurements. Furthermore, the best cutoff values of NC for central obesity identification were determined by applying the receiver operating characteristic (ROC) curve analysis. Results: NC correlated positively with BMI, SBP and WC In both sexes. Both WC and NC correlated significantly positively with IR. A positive correlation between NC and FPG as well as a negative correlation between NC and HDL were found in obese men. NC≥38.5 cm for men and ≥34.5 cm for women were determined to be the best cutoff levels for identifying subjects with central obesity, with 82.9% accuracy for men and 79.9% accuracy for women. Conclusions: NC correlated positively with BMI and WC in both genders, indicating that NC could be used as a valid marker for both overall obesity and central obesity. In addition, measuring NC was shown to be a useful test for IR identification. Large number of NC is suggested to be associated with high risk of developing metabolic disorders, such as diabetes and dyslipidemia. PMID:26770540

  16. Mammalian pheromones.

    PubMed

    Liberles, Stephen D

    2014-01-01

    Mammalian pheromones control a myriad of innate social behaviors and acutely regulate hormone levels. Responses to pheromones are highly robust, reproducible, and stereotyped and likely involve developmentally predetermined neural circuits. Here, I review several facets of pheromone transduction in mammals, including (a) chemosensory receptors and signaling components of the main olfactory epithelium and vomeronasal organ involved in pheromone detection; (b) pheromone-activated neural circuits subject to sex-specific and state-dependent modulation; and (c) the striking chemical diversity of mammalian pheromones, which range from small, volatile molecules and sulfated steroids to large families of proteins. Finally, I review (d) molecular mechanisms underlying various behavioral and endocrine responses, including modulation of puberty and estrous; control of reproduction, aggression, suckling, and parental behaviors; individual recognition; and distinguishing of own species from predators, competitors, and prey. Deconstruction of pheromone transduction mechanisms provides a critical foundation for understanding how odor response pathways generate instinctive behaviors. PMID:23988175

  17. Mammalian Pheromones

    PubMed Central

    Liberles, Stephen D.

    2015-01-01

    Mammalian pheromones control a myriad of innate social behaviors and acutely regulate hormone levels. Responses to pheromones are highly robust, reproducible, and stereotyped and likely involve developmentally predetermined neural circuits. Here, I review several facets of pheromone transduction in mammals, including (a) chemosensory receptors and signaling components of the main olfactory epithelium and vomeronasal organ involved in pheromone detection; (b) pheromone-activated neural circuits subject to sex-specific and state-dependent modulation; and (c) the striking chemical diversity of mammalian pheromones, which range from small, volatile molecules and sulfated steroids to large families of proteins. Finally, I review (d ) molecular mechanisms underlying various behavioral and endocrine responses, including modulation of puberty and estrous; control of reproduction, aggression, suckling, and parental behaviors; individual recognition; and distinguishing of own species from predators, competitors, and prey. Deconstruction of pheromone transduction mechanisms provides a critical foundation for understanding how odor response pathways generate instinctive behaviors. PMID:23988175

  18. Lipoprotein Receptor LRP1 Regulates Leptin Signaling and Energy Homeostasis in the Adult Central Nervous System

    PubMed Central

    Liu, Qiang; Zhang, Juan; Zerbinatti, Celina; Zhan, Yan; Kolber, Benedict J.; Herz, Joachim; Muglia, Louis J.; Bu, Guojun

    2011-01-01

    Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system. PMID:21264353

  19. Expression of Hepatoma-derived growth factor family members in the adult central nervous system

    PubMed Central

    El-Tahir, Heba M; Dietz, Frank; Dringen, Ralf; Schwabe, Kerstin; Strenge, Karen; Kelm, Sørge; Abouzied, Mekky M; Gieselmann, Volkmar; Franken, Sebastian

    2006-01-01

    Background Hepatoma-derived growth factor (HDGF) belongs to a polypeptide family containing five additional members called HDGF related proteins 1–4 (HRP-1 to -4) and Lens epithelial derived growth factor. Whereas some family members such as HDGF and HRP-2 are expressed in a wide range of tissues, the expression of others is very restricted. HRP-1 and -4 are only expressed in testis, HRP-3 only in the nervous system. Here we investigated the expression of HDGF, HRP-2 and HRP-3 in the central nervous system of adult mice on the cellular level by immunohistochemistry. In addition we performed Western blot analysis of various brain regions as well as neuronal and glial cell cultures. Results HDGF was rather evenly expressed throughout all brain regions tested with the lowest expression in the substantia nigra. HRP-2 was strongly expressed in the thalamus, prefrontal and parietal cortex, neurohypophysis, and the cerebellum, HRP-3 in the bulbus olfactorius, piriform cortex and amygdala complex. HDGF and HRP-2 were found to be expressed by neurons, astrocytes and oligodendrocytes. In contrast, strong expression of HRP-3 in the adult nervous system is restricted to neurons, except for very weak expression in oligodendrocytes in the brain stem. Although the majority of neurons are HRP-3 positive, some like cerebellar granule cells are negative. Conclusion The coexpression of HDGF and HRP-2 in glia and neurons as well as the coexpression of all three proteins in many neurons suggests different functions of members of the HDGF protein family in cells of the central nervous system that might include proliferation as well as cell survival. In addition the restricted expression of HRP-3 point to a special function of this family member for neuronal cells. PMID:16430771

  20. Major Dietary Patterns in Relation to General and Central Obesity among Chinese Adults

    PubMed Central

    Yu, Canqing; Shi, Zumin; Lv, Jun; Du, Huaidong; Qi, Lu; Guo, Yu; Bian, Zheng; Chang, Liang; Tang, Xuefeng; Jiang, Qilian; Mu, Huaiyi; Pan, Dongxia; Chen, Junshi; Chen, Zhengming; Li, Liming

    2015-01-01

    Limited evidence exists for the association between diet pattern and obesity phenotypes among Chinese adults. In the present study, we analyzed the cross-sectional data from 474,192 adults aged 30–79 years from the China Kadoorie Biobank baseline survey. Food consumption was collected by an interviewer-administered questionnaire. Three dietary patterns were extracted by factor analysis combined with cluster analysis. After being adjusted for potential confounders, individuals following a traditional southern dietary pattern had the lowest body mass index (BMI) and waist circumference (WC); the Western/new affluence dietary pattern had the highest BMI; and the traditional northern dietary pattern had the highest WC. Compared to the traditional southern dietary pattern in multivariable adjusted logistic models, individuals following a Western/new affluence dietary pattern had a significantly increased risk of general obesity (prevalence ratio (PR): 1.06, 95% confidence interval (CI): 1.03–1.08) and central obesity (PR: 1.07, 95% CI: 1.06–1.08). The corresponding risks for the traditional northern dietary pattern were 1.05 (1.02–1.09) and 1.17 (1.25–1.18), respectively. In addition, the associations were modified by lifestyle behaviors, and the combined effects with alcohol drinking, tobacco smoking, and physical activity were analyzed. Further prospective studies are needed to elucidate the diet-obesity relationships. PMID:26184308

  1. Major Dietary Patterns in Relation to General and Central Obesity among Chinese Adults.

    PubMed

    Yu, Canqing; Shi, Zumin; Lv, Jun; Du, Huaidong; Qi, Lu; Guo, Yu; Bian, Zheng; Chang, Liang; Tang, Xuefeng; Jiang, Qilian; Mu, Huaiyi; Pan, Dongxia; Chen, Junshi; Chen, Zhengming; Li, Liming

    2015-07-01

    Limited evidence exists for the association between diet pattern and obesity phenotypes among Chinese adults. In the present study, we analyzed the cross-sectional data from 474,192 adults aged 30-79 years from the China Kadoorie Biobank baseline survey. Food consumption was collected by an interviewer-administered questionnaire. Three dietary patterns were extracted by factor analysis combined with cluster analysis. After being adjusted for potential confounders, individuals following a traditional southern dietary pattern had the lowest body mass index (BMI) and waist circumference (WC); the Western/new affluence dietary pattern had the highest BMI; and the traditional northern dietary pattern had the highest WC. Compared to the traditional southern dietary pattern in multivariable adjusted logistic models, individuals following a Western/new affluence dietary pattern had a significantly increased risk of general obesity (prevalence ratio (PR): 1.06, 95% confidence interval (CI): 1.03-1.08) and central obesity (PR: 1.07, 95% CI: 1.06-1.08). The corresponding risks for the traditional northern dietary pattern were 1.05 (1.02-1.09) and 1.17 (1.25-1.18), respectively. In addition, the associations were modified by lifestyle behaviors, and the combined effects with alcohol drinking, tobacco smoking, and physical activity were analyzed. Further prospective studies are needed to elucidate the diet-obesity relationships. PMID:26184308

  2. Central Nervous System Involvement in Adult Acute Lymphoblastic Leukemia: Diagnostic Tools, Prophylaxis, and Therapy

    PubMed Central

    Del Principe, Maria Ilaria; Maurillo, Luca; Buccisano, Francesco; Sconocchia, Giuseppe; Cefalo, Mariagiovanna; De Santis, Giovanna; Di Veroli, Ambra; Ditto, Concetta; Nasso, Daniela; Postorino, Massimiliano; Refrigeri, Marco; Attrotto, Cristina; Del Poeta, Giovanni; Lo-Coco, Francesco; Amadori, Sergio; Venditti, Adriano

    2014-01-01

    In adult patients with acute lymphoblastic leukemia (ALL), Central Nervous System (CNS) involvement is associated with a very poor prognosis. The diagnostic assessment of this condition relies on the use of neuroradiology, conventional cytology (CC) and flow cytometry (FCM). Among these approaches, which is the gold standard it is still a matter of debate. Neuroradiology and CC have a limited sensitivity with a higher rate of false negative results. FCM demonstrated a superior sensitivity over CC, particularly when low levels of CNS infiltrating cells are present. Although prospective studies of a large series of patients are still awaited, a positive finding by FCM appears to anticipate an adverse outcome even if CC shows no infiltration. Current strategies for adult ALL CNS-directed prophylaxis or therapy involve systemic and intrathecal chemotherapy and radiation therapy. An early and frequent intrathecal injection of cytostatic combined with systemic chemotherapy is the most effective strategy to reduce the frequency of CNS involvement. In patients with CNS overt ALL, at diagnosis or upon relapse, allogeneic hematopoietic stem cell transplantation might be considered. This review discusses risk factors, diagnostic techniques for identification of CNS infiltration and modalities of prophylaxis and therapy to manage it. PMID:25408861

  3. Clinical presentation, etiology, and survival in adult acute encephalitis syndrome in rural Central India

    PubMed Central

    Joshi, Rajnish; Mishra, Pradyumna Kumar; Joshi, Deepti; Santhosh, SR; Parida, M.M.; Desikan, Prabha; Gangane, Nitin; Kalantri, S.P.; Reingold, Arthur; Colford, John M.

    2013-01-01

    Background Acute encephalitis syndrome (AES) is a constellation of symptoms that includes fever and altered mental status. Most cases are attributed to viral encephalitis (VE), occurring either in outbreaks or sporadically. We conducted hospital-based surveillance for sporadic adult-AES in rural Central India in order to describe its incidence, spatial and temporal distribution, clinical profile, etiology and predictors of mortality. Methods All consecutive hospital admissions during the study period were screened to identify adult-AES cases and were followed until 30-days of hospitalization. We estimated incidence by administrative sub-division of residence and described the temporal distribution of cases. We performed viral diagnostic studies on cerebrospinal fluid (CSF) samples to determine the etiology of AES. The diagnostic tests included RT-PCR (for enteroviruses, HSV 1 and 2), conventional PCR (for flaviviruses), CSF IgM capture ELISA (for Japanese encephalitis virus, dengue, West Nile virus, Varicella zoster virus, measles, and mumps). We compared demographic and clinical variables across etiologic subtypes and estimated predictors of 30-day mortality. Results A total of 183 AES cases were identified between January and October 2007, representing 2.38% of all admissions. The incidence of adult AES in the administrative subdivisions closest to the hospital was 16 per 100,000. Of the 183 cases, a non-viral etiology was confirmed in 31 (16.9%) and the remaining 152 were considered as VE suspects. Of the VE suspects, we could confirm a viral etiology in 31 cases: 17 (11.2%) enterovirus; 8 (5.2%) flavivirus; 3 (1.9%) Varicella zoster; 1 (0.6%) herpesvirus; and 2 (1.3%) mixed etiology); the etiology remained unknown in remaining 121 (79.6%) cases. 53 (36%) of the AES patients died; the case fatality proportion was similar in patients with a confirmed and unknown viral etiology (45.1 and 33.6% respectively). A requirement for assisted ventilation significantly

  4. Effects of Neuroendocrine CB1 Activity on Adult Leydig Cells

    PubMed Central

    Cobellis, Gilda; Meccariello, Rosaria; Chianese, Rosanna; Chioccarelli, Teresa; Fasano, Silvia; Pierantoni, Riccardo

    2016-01-01

    Endocannabinoids control male reproduction acting at central and local level via cannabinoid receptors. The cannabinoid receptor CB1 has been characterized in the testis, in somatic and germ cells of mammalian and non-mammalian animal models, and its activity related to Leydig cell differentiation, steroidogenesis, spermiogenesis, sperm quality, and maturation. In this short review, we provide a summary of the insights concerning neuroendocrine CB1 activity in male reproduction focusing on adult Leydig cell ontogenesis and steroid biosynthesis. PMID:27375550

  5. Effects of Neuroendocrine CB1 Activity on Adult Leydig Cells.

    PubMed

    Cobellis, Gilda; Meccariello, Rosaria; Chianese, Rosanna; Chioccarelli, Teresa; Fasano, Silvia; Pierantoni, Riccardo

    2016-01-01

    Endocannabinoids control male reproduction acting at central and local level via cannabinoid receptors. The cannabinoid receptor CB1 has been characterized in the testis, in somatic and germ cells of mammalian and non-mammalian animal models, and its activity related to Leydig cell differentiation, steroidogenesis, spermiogenesis, sperm quality, and maturation. In this short review, we provide a summary of the insights concerning neuroendocrine CB1 activity in male reproduction focusing on adult Leydig cell ontogenesis and steroid biosynthesis. PMID:27375550

  6. Adult Education Research in the Countries in Transition. Adult Education Research Trends in the Former Socialist Countries of Central and Eastern Europe and the Baltic Region. Research Project Report. Studies and Researches 6.

    ERIC Educational Resources Information Center

    Jelenc, Zoran

    This document presents results of an investigation into the state of the art of research on the education of adults in Central and Eastern European and Baltic countries. The first section discusses the background and implementation of the research. Section 2 is "Adult Education Research Trends in Central and Eastern Europe: Research Project…

  7. Mammalian aromatases.

    PubMed

    Conley, A; Hinshelwood, M

    2001-05-01

    Aromatase is the enzyme complex that catalyses the synthesis of oestrogens from androgens, and therefore it has unique potential to influence the physiological balance between the sex steroid hormones. Both aromatase cytochrome P450 (P450arom) and NADPH-cytochrome P450 reductase (reductase), the two essential components of the enzyme complex, are highly conserved among mammals and vertebrates. Aromatase expression occurs in the gonads and brain, and is essential for reproductive development and fertility. Of interest are the complex mechanisms involving alternative promoter utilization that have evolved to control tissue-specific expression in these tissues. In addition, in a number of species, including humans, expression of aromatase has a broader tissue distribution, including placenta, adipose and bone. The relevance of oestrogen synthesis and possibly androgen metabolism in these peripheral sites of expression is now becoming clear from studies in P450arom knockout (ArKO) mice and from genetic defects recognized recently in both men and women. Important species differences in the physiological roles of aromatase expression are also likely to emerge, despite the highly conserved nature of the enzyme system. The identification of functionally distinct, tissue-specific isozymes of P450arom in at least one mammal, pigs, and several species of fish indicates that there are additional subtle, but physiologically significant, species-specific roles for aromatase. Comparative studies of mammalian and other vertebrate aromatases will expand understanding of the role played by this ancient enzyme system in the evolution of reproduction and the adaptive influence of oestrogen synthesis on general health and well being. PMID:11427156

  8. Identification of PGAM5 as a Mammalian Protein Histidine Phosphatase that Plays a Central Role to Negatively Regulate CD4(+) T Cells.

    PubMed

    Panda, Saswati; Srivastava, Shekhar; Li, Zhai; Vaeth, Martin; Fuhs, Stephen R; Hunter, Tony; Skolnik, Edward Y

    2016-08-01

    Whereas phosphorylation of serine, threonine, and tyrosine is exceedingly well characterized, the role of histidine phosphorylation in mammalian signaling is largely unexplored. Here we show that phosphoglycerate mutase family 5 (PGAM5) functions as a phosphohistidine phosphatase that specifically associates with and dephosphorylates the catalytic histidine on nucleoside diphosphate kinase B (NDPK-B). By dephosphorylating NDPK-B, PGAM5 negatively regulates CD4(+) T cells by inhibiting NDPK-B-mediated histidine phosphorylation and activation of the K(+) channel KCa3.1, which is required for TCR-stimulated Ca(2+) influx and cytokine production. Using recently developed monoclonal antibodies that specifically recognize phosphorylation of nitrogens at the N1 (1-pHis) or N3 (3-pHis) positions of the imidazole ring, we detect for the first time phosphoisoform-specific regulation of histidine-phosphorylated proteins in vivo, and we link these modifications to TCR signaling. These results represent an important step forward in studying the role of histidine phosphorylation in mammalian biology and disease. PMID:27453048

  9. Determinants of HIV-related cardiac disease among adults in north central Nigeria

    PubMed Central

    Isiguzo, Godsent; Okeahialam, Basil; Danbauchi, Solomon; Odili, Augustin; Iroezindu, Michael

    2013-01-01

    Objective The aim of the present study was to evaluate the determinants of HIV-related cardiac disease (HRCD) among adults in north central Nigeria. This was a hospital-based cross-sectional study recruiting patients who were HIV positive attending the HIV clinic at Jos University teaching Hospital, Nigeria. Methods A total of 200 adults who were HIV positive and aged ≥18 years were consecutively recruited. All patients were administered a questionnaire and underwent clinical examination, laboratory investigation for haemoglobin estimation, CD4 cell count, viral load, serum lipid profile, hepatitis B surface antigen, anti-hepatitis C virus antibody, electrocardiogram and two-dimensional echocardiography Doppler studies. The outcome measure was echocardiography-defined cardiac disease, such as systolic dysfunction, diastolic dysfunction, isolated left ventricular dilatation, right ventricular dysfunction or pulmonary hypertension. Results The mean age of the study population was 38±9 years. The majority (71%) were women and were on average younger than the men (36±8 years vs 47±9 years, p<0.0002). Highly active anti-retroviral therapy (HAART) use was seen in 84.4% of subjects. The median CD4 cell count for the study population was 358 cells/µL; the count was 459 (95% CI 321 to 550) cells/µL for subjects without HRCD and 193 (95% CI 126 to 357) cells/µL for subjects with HRCD (p<0.001). HAART-naive subjects with HRCD had a mean CD4 cell count of 121 cells/µL vs 200 cells/µL for those on HAART (p<0.01). CD4 cell count (OR = 0.25, 95% CI 0.15 to 0.45) and duration of diagnosis (OR=3.88, 95% CI 1.20 to 13.71) were the significant determinants of HRCD on multivariate analysis. Conclusions Duration of HIV diagnosis and degree of immunosuppression were the significant determinants of HRCD. There is therefore a need to reduce cardiovascular morbidity in patients infected with HIV through early diagnosis/sustained use of HAART, early screening for HRCD

  10. Liposomal cytarabine for central nervous system embryonal tumors in children and young adults.

    PubMed

    Partap, Sonia; Murphy, Patricia A; Vogel, Hannes; Barnes, Patrick D; Edwards, Michael S B; Fisher, Paul G

    2011-07-01

    To assess the tolerability and efficacy of liposomal cytarabine (LC), an encapsulated, sustained-release, intrathecal (IT) formulation of cytosine arabinoside, in de novo and relapsed central nervous system (CNS) embryonal tumors in children and young adults. We studied retrospectively all patients less than age 30 at our institution treated consecutively with LC for medulloblastoma (MB), primitive neuroectodermal tumor (PNET), and atypical teratoid rhabdoid tumor (ATRT). Seventeen patients received LC (2 mg/kg up to 50 mg, every 2 weeks to monthly) at diagnosis of high-risk CNS embryonal tumor (2 PNET, 3 ATRT) or relapse of MB (12 MB; 9 had leptomeningeal metastases). Sixteen patients received concurrent systemic chemotherapy. A total of 108 doses were administered (IT 82, intraventricular 26) with a mean of six (range 1-16) treatments per patient. Only three administrations were associated with adverse effects of arachnoiditis or headache. None developed malignant cerebrospinal fluid (CSF) cytology while receiving LC. All the six evaluable patients with malignant CSF cytology and treated with at least two doses cleared their CSF (mean 3 doses, range 1-5). Median overall survival in relapse patients was 9.1 months. Five patients (4 de novo and 1 relapsed) remain alive in complete remission for a median 26.8 months from first LC. Liposomal cytarabine is an easily administered, well-tolerated, and active drug in patients with high-risk embryonal neoplasms. One-third of our cohort remains in remission from otherwise fatal diagnoses. Our findings warrant a phase II trial of LC in newly diagnosed or recurrent CNS embryonal tumors. PMID:20859651

  11. Mammalian phospholipase C.

    PubMed

    Kadamur, Ganesh; Ross, Elliott M

    2013-01-01

    Phospholipase C (PLC) converts phosphatidylinositol 4,5-bisphosphate (PIP(2)) to inositol 1,4,5-trisphosphate (IP(3)) and diacylglycerol (DAG). DAG and IP(3) each control diverse cellular processes and are also substrates for synthesis of other important signaling molecules. PLC is thus central to many important interlocking regulatory networks. Mammals express six families of PLCs, each with both unique and overlapping controls over expression and subcellular distribution. Each PLC also responds acutely to its own spectrum of activators that includes heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins, Ca(2+), and phospholipids. Mammalian PLCs are autoinhibited by a region in the catalytic TIM barrel domain that is the target of much of their acute regulation. In combination, the PLCs act as a signaling nexus that integrates numerous signaling inputs, critically governs PIP(2) levels, and regulates production of important second messengers to determine cell behavior over the millisecond to hour timescale. PMID:23140367

  12. An Update of the Mayo Clinic Cohort of Patients With Adult Primary Central Nervous System Vasculitis

    PubMed Central

    Salvarani, Carlo; Brown, Robert D.; Christianson, Teresa; Miller, Dylan V.; Giannini, Caterina; Huston, John; Hunder, Gene G.

    2015-01-01

    Abstract Primary central nervous system vasculitis (PCNSV) is an uncommon condition in which lesions are limited to vessels of the brain and spinal cord. Because the clinical manifestations are not specific, the diagnosis is often difficult, and permanent disability and death are frequent outcomes. This study is based on a cohort of 163 consecutive patients with PCNSV who were examined at the Mayo Clinic over a 29-year period from 1983 to 2011. The aim of the study was to define the characteristics of these patients, which represents the largest series in adults reported to date. A total of 105 patients were diagnosed by angiographic findings and 58 by biopsy results. The patients diagnosed by biopsy more frequently had at presentation cognitive dysfunction, greater cerebrospinal fluid total protein concentrations, less frequent cerebral infarcts, and more frequent leptomeningeal gadolinium-enhanced lesions on magnetic resonance imaging (MRI), along with less mortality and disability at last follow-up. The patients diagnosed by angiograms more frequently had at presentation hemiparesis or a persistent neurologic deficit or stroke, more frequent infarcts on MRI and an increased mortality. These differences were mainly related to the different size of the vessels involved in the 2 groups. Although most patients responded to therapy with glucocorticoids alone or in conjunction with cyclophosphamide and tended to improve during the follow-up period, an overall increased mortality rate was observed. Relapses occurred in one-quarter of the patients and were less frequent in patients treated with prednisone and cyclophosphamide compared with those treated with prednisone alone. The mortality rate and degree of disability at last follow-up were greater in those with increasing age, cerebral infarctions on MRI, angiographic large vessel involvement, and diagnosis made by angiography alone, but were lower in those with gadolinium-enhanced lesions on MRI and in those with

  13. Impact of Treatment Site in Adolescents and Young Adults With Central Nervous System Tumors

    PubMed Central

    Wolfson, Julie; Sun, Can-Lan; Kang, Tongjun; Wyatt, Laura; D’Appuzzo, Massimo

    2014-01-01

    Background Adolescents and young adults (AYAs; aged 15–39 years) have inferior survival in comparison with younger (aged 0–14 years) cancer patients. Impact of care at specialized centers such as National Cancer Institute–designated Comprehensive Cancer Centers (NCICCC) for AYAs of all ages or the Children’s Oncology Group (COG) for AYAs aged 15 to 21 years with central nervous system (CNS) tumors remains unstudied. Methods We constructed a cohort of 560 children and 784 AYAs with CNS tumors reported to the Los Angeles cancer registry from 1998 to 2008. Cox and logistic regression models were used, with two-sided P values from Wald χ2 tests. Results In Cox regression analysis restricted to World Health Organization (WHO) grade II tumors, patients of all ages saw worse outcome if not treated at NCICCC/COG sites (non-NCICCC/COG vs NCICCC/COG: hazard ratio [HR] =1.73; 95% confidence interval [CI] = 1.09 to 2.72). Furthermore, the worse outcome for AYAs compared with children (HR = 1.90; 95% CI = 1.21 to 2.98; P = .005) was abrogated (HR = 1.35; 95% CI = 0.79 to 2.29; P = .27) by care at NCICCC/COGs. Those less likely to receive care at NCICCC/COG sites included young AYAs (aged 15–21 years vs children: odds ratio [OR] = 0.23; 95% CI = 0.11 to 0.48; P < .001) and older AYAs (aged 22–39 years) with low socioeconomic status (OR = 0.39; 95% CI = 0.17 to 0.89; P = .02), public/no insurance (OR = 0.30; 95% CI = 0.12 to 0.71; P < .01), and distance to care greater than 5 miles (OR = 0.29; 95% CI = 0.15 to 0.57; P < .001). Conclusions Population-based data reveal that care at NCICCC/COG sites mitigates inferior outcome in AYAs with WHO grade II CNS tumors compared with children. Compared with children, AYAs are less likely to receive care at NCICCC/COGs. Insurance, socioeconomic status, and distance serve as barriers to care at NCICCCs for older AYAs. PMID:25178694

  14. Abnormal degree centrality of functional hubs associated with negative coping in older Chinese adults who lost their only child.

    PubMed

    Liu, Wei; Liu, HuiJuan; Wei, Dongtao; Sun, Jiangzhou; Yang, Junyi; Meng, Jie; Wang, Lihong; Qiu, Jiang

    2015-12-01

    The loss of an only child is a negative life event and may potentially increase the risk of psychiatric disorders. However, the psychological consequences of the loss of an only child and the associated neural mechanisms remain largely unexplored. Degree centrality (DC), derived from resting-state functional magnetic resonance imaging (fMRI), was used to examine network communication in 22 older adults who lost their only child and 23 matched controls. The older adults who lost their only child exhibited an ineffective coping style. They also showed decreased distant and local DC in the precuneus and left inferior parietal lobule and decreased distant DC in the bilateral dorsolateral prefrontal cortex (DLPFC). Furthermore, the decreased local and distant DC of these regions and the decreased DLPFC-precuneus connectivity strength were negatively correlated with negative coping scores in the loss group but not in the controls. Overall, the results suggested a model that the impaired neural network communication of brain hubs within the default mode network (DMN) and central executive network (CEN) were associated with a negative coping style in older adults who lost their only child. The decreased connectivity of the hubs can be identified as a neural risk factor that is related to future psychopathology. PMID:26391339

  15. The acute effect of maximal exercise on central and peripheral arterial stiffness indices and hemodynamics in children and adults.

    PubMed

    Melo, Xavier; Fernhall, Bo; Santos, Diana A; Pinto, Rita; Pimenta, Nuno M; Sardinha, Luís B; Santa-Clara, Helena

    2016-03-01

    This study compared the effects of a bout of maximal running exercise on arterial stiffness in children and adults. Right carotid blood pressure and artery stiffness indices measured by pulse wave velocity (PWV), compliance and distensibility coefficients, stiffness index α and β (echo-tracking), contralateral carotid blood pressure, and upper and lower limb and central/aortic PWV (applanation tonometry) were taken at rest and 10 min after a bout of maximal treadmill running in 34 children (7.38 ± 0.38 years) and 45 young adults (25.22 ± 0.91 years) having similar aerobic potential. Two-by-two repeated measures analysis of variance and analysis of covariance were used to detect differences with exercise between groups. Carotid pulse pressure (PP; η(2) = 0.394) increased more in adults after exercise (p < 0.05). Compliance (η(2) = 0.385) decreased in particular in adults and in those with high changes in distending pressure, similarly to stiffness index α and β. Carotid PWV increased more in adults and was related to local changes in PP but not mean arterial pressure (MAP). Stiffness in the lower limbs decreased (η(2) = 0.115) but apparently only in those with small MAP changes (η(2) = 0.111). No significant exercise or group interaction effects were found when variables were adjusted to height. An acute bout of maximal exercise can alter arterial stiffness and hemodynamics in the carotid artery and within the active muscle beds. Arterial stiffness and hemodynamic response to metabolic demands during exercise in children simply reflect their smaller body size and may not indicate a particular physiological difference compared with adults. PMID:26842667

  16. Proliferation, neurogenesis and regeneration in the non-mammalian vertebrate brain.

    PubMed

    Kaslin, Jan; Ganz, Julia; Brand, Michael

    2008-01-12

    and also the greatest capacity to regenerate central nervous system injuries. Studying these phenomena in non-mammalian vertebrates may greatly increase our understanding of the mechanisms underlying regeneration and adult neurogenesis. Understanding mechanisms that regulate endogenous proliferation and neurogenic permissiveness in the adult brain is of great significance in therapeutical approaches for brain injury and disease. PMID:17282988

  17. Hemispheric Lateralization of Bilaterally Presented Homologous Visual and Auditory Stimuli in Normal Adults, Normal Children, and Children with Central Auditory Dysfunction

    ERIC Educational Resources Information Center

    Bellis, Teri James; Billiet, Cassie; Ross, Jody

    2008-01-01

    Two experiments were conducted to examine the performance of normal adults, normal children, and children diagnosed with central auditory dysfunction presumed to involve the interhemispheric pathways on a dichotic digits test in common clinical use for the diagnosis of central auditory processing disorder (CAPD) and its corresponding visual…

  18. A Sodium Leak Current Regulates Pacemaker Activity of Adult Central Pattern Generator Neurons in Lymnaea Stagnalis

    PubMed Central

    Lu, Tom Z.; Feng, Zhong-Ping

    2011-01-01

    The resting membrane potential of the pacemaker neurons is one of the essential mechanisms underlying rhythm generation. In this study, we described the biophysical properties of an uncharacterized channel (U-type channel) and investigated the role of the channel in the rhythmic activity of a respiratory pacemaker neuron and the respiratory behaviour in adult freshwater snail Lymnaea stagnalis. Our results show that the channel conducts an inward leak current carried by Na+ (ILeak-Na). The ILeak-Na contributed to the resting membrane potential and was required for maintaining rhythmic action potential bursting activity of the identified pacemaker RPeD1 neurons. Partial knockdown of the U-type channel suppressed the aerial respiratory behaviour of the adult snail in vivo. These findings identified the Na+ leak conductance via the U-type channel, likely a NALCN-like channel, as one of the fundamental mechanisms regulating rhythm activity of pacemaker neurons and respiratory behaviour in adult animals. PMID:21526173

  19. An overview of mammalian pluripotency.

    PubMed

    Wu, Jun; Yamauchi, Takayoshi; Izpisua Belmonte, Juan Carlos

    2016-05-15

    Mammalian pluripotency is the ability to give rise to all somatic cells as well as the germ cells of an adult mammal. It is a unique feature of embryonic epiblast cells, existing only transiently, as cells pass through early developmental stages. By contrast, pluripotency can be captured and stabilized indefinitely in cell culture and can also be reactivated in differentiated cells via nuclear reprogramming. Pluripotent stem cells (PSCs) are the in vitro carriers of pluripotency and they can inhabit discrete pluripotent states depending on the stage at which they were derived and their culture conditions. Here, and in the accompanying poster, we provide a summary of mammalian pluripotency both in vivo and in vitro, and highlight recent and future applications of PSCs for basic and translational research. PMID:27190034

  20. Efficient central nervous system AAVrh10-mediated intrathecal gene transfer in adult and neonate rats.

    PubMed

    Hordeaux, J; Dubreil, L; Deniaud, J; Iacobelli, F; Moreau, S; Ledevin, M; Le Guiner, C; Blouin, V; Le Duff, J; Mendes-Madeira, A; Rolling, F; Cherel, Y; Moullier, P; Colle, M-A

    2015-04-01

    Intracerebral administration of recombinant adeno-associated vector (AAV) has been performed in several clinical trials. However, delivery into the brain requires multiple injections and is not efficient to target the spinal cord, thus limiting its applications. To assess widespread and less invasive strategies, we tested intravenous (IV) or intrathecal (that is, in the cerebrospinal fluid (CSF)) delivery of a rAAVrh10-egfp vector in adult and neonate rats and studied the effect of the age at injection on neurotropism. IV delivery is more efficient in neonates and targets predominantly Purkinje cells of the cerebellum and sensory neurons of the spinal cord and dorsal root ganglia. A single intra-CSF administration of AAVrh10, single strand or oversized self-complementary, is efficient for the targeting of neurons in the cerebral hemispheres, cerebellum, brainstem and spinal cord. Green fluorescent protein (GFP) expression is more widespread in neonates when compared with adults. More than 50% of motor neurons express GFP in the three segments of the spinal cord in neonates and in the cervical and thoracic regions in adults. Neurons are almost exclusively transduced in neonates, whereas neurons, astrocytes and rare oligodendrocytes are targeted in adults. These results expand the possible routes of delivery of AAVrh10, a serotype that has shown efficacy and safety in clinical trials concerning neurodegenerative diseases. PMID:25588740

  1. Mammalian Carboxylesterase 5: Comparative Biochemistry and Genomics

    PubMed Central

    Holmes, Roger S; Cox, Laura A; VandeBerg, John L

    2008-01-01

    Carboxylesterase 5 (CES5) (also called cauxin or CES7) is one of at least five mammalian CES gene families encoding enzymes of broad substrate specificity and catalysing hydrolytic and transesterification reactions. In silico methods were used to predict the amino acid sequences, secondary structures and gene locations for CES5 genes and gene products. Amino acid sequence alignments of mammalian CES5 enzymes enabled identification of key CES sequences previously reported for human CES1, as well as other sequences that are specific to the CES5 gene family, which were consistent with being monomeric in subunit structure and available for secretion into body fluids. Predicted secondary structures for mammalian CES5 demonstrated significant conservation with human CES1 as well as distinctive mammalian CES5 like structures. Mammalian CES5 genes are located in tandem with the CES1 gene(s), are transcribed on the reverse strand and contained 13 exons. CES5 has been previously reported in high concentrations in the urine (cauxin) of adult male cats, and within a protein complex of mammalian male epididymal fluids. Roles for CES5 may include regulating urinary levels of male cat pheromones; catalysing lipid transfer reactions within mammalian male reproductive fluids; and protecting neural tissue from drugs and xenobiotics. PMID:19727319

  2. Environmental noise and cardiovascular disease in adults: research in Central, Eastern and South-Eastern Europe and Newly Independent States.

    PubMed

    Argalášová-Sobotová, L'ubica; Lekaviciute, Jurgita; Jeram, Sonja; Sevcíková, L'udmila; Jurkovicová, Jana

    2013-01-01

    The adverse effects of noise on health have been intensely explored in the past 50 years. However, the scope of research conducted in the Central and Eastern Europe, South-East Europe, and Newly Independent States is not well-known. The aim of this review was to present studies on cardiovascular effects of environmental noise in adults published since 1965 and to point out the most important issues that need to be addressed in the future. More than 100 papers on noise and health and about 20 papers on cardiovascular effects of environmental noise in adults were identified by literature search. The authors reviewed scientific international and local journals, conference proceedings, and local reports published in national languages. The major endpoints were high blood pressure, ischemic heart disease, and myocardial infarction. The target populations were adults. Experimental and exposure-assessment studies, field, empirical studies, social surveys, and epidemiological studies are presented. The major sources of environmental noise were road and air traffic. The results were presented in tables and the most relevant articles were briefly discussed. The importance of this review is that it refers to some countries that no longer exist in the same political and governmental systems. The strength of this paper is that it includes publications that were not evaluated in earlier systematic reviews. Strategies for future noise-related research on national and global level are proposed. PMID:23412577

  3. Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats.

    PubMed

    Kaplan, Kara; Echert, Ashley E; Massat, Ben; Puissant, Madeleine M; Palygin, Oleg; Geurts, Aron M; Hodges, Matthew R

    2016-05-01

    Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DA(Tph2-/-)) rats. DA(Tph2-/-) rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (∼50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DA(Tph2-/-) rats. Body temperature was also maintained in adult DA(Tph2-/-) rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DA(Tph2-/-) rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat. PMID:26869713

  4. Tuning and playing a motor rhythm: how metabotropic glutamate receptors orchestrate generation of motor patterns in the mammalian central nervous system.

    PubMed

    Nistri, Andrea; Ostroumov, Konstantin; Sharifullina, Elina; Taccola, Giuliano

    2006-04-15

    Repeated motor activities like locomotion, mastication and respiration need rhythmic discharges of functionally connected neurons termed central pattern generators (CPGs) that cyclically activate motoneurons even in the absence of descending commands from higher centres. For motor pattern generation, CPGs require integration of multiple processes including activation of ion channels and transmitter receptors at strategic locations within motor networks. One emerging mechanism is activation of glutamate metabotropic receptors (mGluRs) belonging to group I, while group II and III mGluRs appear to play an inhibitory function on sensory inputs. Group I mGluRs generate neuronal membrane depolarization with input resistance increase and rapid fluctuations in intracellular Ca(2+), leading to enhanced excitability and rhythmicity. While synchronicity is probably due to modulation of inhibitory synaptic transmission, these oscillations occurring in coincidence with strong afferent stimuli or application of excitatory agents can trigger locomotor-like patterns. Hence, mGluR-sensitive spinal oscillators play a role in accessory networks for locomotor CPG activation. In brainstem networks supplying tongue muscle motoneurons, group I receptors facilitate excitatory synaptic inputs and evoke synchronous oscillations which stabilize motoneuron firing at regular, low frequency necessary for rhythmic tongue contractions. In this case, synchronicity depends on the strong electrical coupling amongst motoneurons rather than inhibitory transmission, while cyclic activation of K(ATP) conductances sets its periodicity. Activation of mGluRs is therefore a powerful strategy to trigger and recruit patterned discharges of motoneurons. PMID:16469790

  5. Assessment of Crop Damage by Protected Wild Mammalian Herbivores on the Western Boundary of Tadoba-Andhari Tiger Reserve (TATR), Central India

    PubMed Central

    Bayani, Abhijeet; Tiwade, Dilip; Dongre, Ashok; Dongre, Aravind P.; Phatak, Rasika; Watve, Milind

    2016-01-01

    Crop raiding by wild herbivores close to an area of protected wildlife is a serious problem that can potentially undermine conservation efforts. Since there is orders of magnitude difference between farmers’ perception of damage and the compensation given by the government, an objective and realistic estimate of damage was found essential. We employed four different approaches to estimate the extent of and patterns in crop damage by wild herbivores along the western boundary of Tadoba-Andhari Tiger Reserve in the state of Maharashtra, central India. These approaches highlight different aspects of the problem but converge on an estimated damage of over 50% for the fields adjacent to the forest, gradually reducing in intensity with distance. We found that the visual damage assessment method currently employed by the government for paying compensation to farmers was uncorrelated to and grossly underestimated actual damage. The findings necessitate a radical rethinking of policies to assess, mitigate as well as compensate for crop damage caused by protected wildlife species. PMID:27093293

  6. Assessment of Crop Damage by Protected Wild Mammalian Herbivores on the Western Boundary of Tadoba-Andhari Tiger Reserve (TATR), Central India.

    PubMed

    Bayani, Abhijeet; Tiwade, Dilip; Dongre, Ashok; Dongre, Aravind P; Phatak, Rasika; Watve, Milind

    2016-01-01

    Crop raiding by wild herbivores close to an area of protected wildlife is a serious problem that can potentially undermine conservation efforts. Since there is orders of magnitude difference between farmers' perception of damage and the compensation given by the government, an objective and realistic estimate of damage was found essential. We employed four different approaches to estimate the extent of and patterns in crop damage by wild herbivores along the western boundary of Tadoba-Andhari Tiger Reserve in the state of Maharashtra, central India. These approaches highlight different aspects of the problem but converge on an estimated damage of over 50% for the fields adjacent to the forest, gradually reducing in intensity with distance. We found that the visual damage assessment method currently employed by the government for paying compensation to farmers was uncorrelated to and grossly underestimated actual damage. The findings necessitate a radical rethinking of policies to assess, mitigate as well as compensate for crop damage caused by protected wildlife species. PMID:27093293

  7. College and Adult Reading XII: The Twelfth Yearbook of the North Central Reading Association.

    ERIC Educational Resources Information Center

    Fisher, Joseph A., Ed.

    Consisting of a selection of papers presented at the 1982 and 1983 meetings of the North Central Reading Association, this yearbook includes sections on computers, research, professional issues, and programs. Papers include: "The Computerized Broom Will Sweep Our Future Classrooms: But Not Necessarily Clean" (George E. Mason); "Beyond the…

  8. College and Adult Reading XIII: The Thirteenth Yearbook of the North Central Reading Association.

    ERIC Educational Resources Information Center

    Fisher, Joseph A., Ed.

    Containing selections of the papers presented at the 1984 and 1985 annual meetings of the North Central Reading Association, this yearbook includes sections on research; reviews of research; professional issues; and program descriptions. Papers include: "Twenty-Five Years of Professional Progress" (James E. Walker); "A Study of Student Alienation…

  9. College and Adult Reading VII: The Seventh Yearbook of the North Central Reading Association.

    ERIC Educational Resources Information Center

    Wark, David M., Ed.

    Spanning the annual meetings of the North Central Reading Association from 1971 to 1974, this yearbook presents papers dealing with programs and centers, materials and techniques, a new research field, and in honor of Roger S. Pepper. Papers include: "Attitudinal Factors among Marginal Admission Students" (Roger S. Pepper and John A. Drexler,…

  10. College and Adult Reading IX: The Ninth Yearbook of the North Central Reading Association.

    ERIC Educational Resources Information Center

    Fisher, Joseph A., Ed.

    Drawn from presentations at the 1977 meeting of the North Central Reading Association, this yearbook includes sections on programs and centers; professional training; clinical problems and methods; research; the Roger Pepper Research Award presentation; and the invitational address. Papers include: "Use of Galvanic Skin Response, Heart Rate,…

  11. College and Adult Reading X: The Tenth Yearbook of the North Central Reading Association.

    ERIC Educational Resources Information Center

    Fisher, Joseph A., Ed.

    Including sections on research, programs, and professional problems and issues, this yearbook contains presentations given at the 1978 and 1979 meetings of the North Central Reading Association. Papers include: "The Effects of Anxiety on Reading Comprehension" (David Wark and others); "Some Effects of Anxiety on University Students" (J. Michael…

  12. College and Adult Reading VIII: The Eighth Yearbook of the North Central Reading Association.

    ERIC Educational Resources Information Center

    Fisher, Joseph A., Ed.

    Drawn from the presentations at the eighteenth and nineteenth annual conferences of the North Central Reading Association, this yearbook includes sections on programs and centers; materials and techniques; evaluation; and professional growth and issues. Papers include: "Successfully Effecting Change on Personality Variables through Academic Skills…

  13. College and Adult Reading XIV: The Fourteenth Yearbook of the North Central Reading Association.

    ERIC Educational Resources Information Center

    Fisher, Kay E., Ed.; Fisher, Joseph A., Ed.

    Containing selections from the 1987 and 1988 annual meetings of the North Central Reading Association, this yearbook includes sections on research; reviews of research; professional issues; and program descriptions. Papers include: "The Effects of a Secondary Reading Methods Course on Undergraduate Students' Awareness of Reading Skills" (Bruce A.…

  14. Ramsay Hunt Syndrome Associated with Central Nervous System Involvement in an Adult.

    PubMed

    Chan, Tommy L H; Cartagena, Ana M; Bombassaro, Anne Marie; Hosseini-Moghaddam, Seyed M

    2016-01-01

    Ramsay Hunt syndrome associated with varicella zoster virus reactivation affecting the central nervous system is rare. We describe a 55-year-old diabetic female who presented with gait ataxia, right peripheral facial palsy, and painful vesicular lesions involving her right ear. Later, she developed dysmetria, fluctuating diplopia, and dysarthria. Varicella zoster virus was detected in the cerebrospinal fluid by polymerase chain reaction. She was diagnosed with Ramsay Hunt syndrome associated with spread to the central nervous system. Her facial palsy completely resolved within 48 hours of treatment with intravenous acyclovir 10 mg/kg every 8 hours. However, cerebellar symptoms did not improve until a tapering course of steroid therapy was initiated. PMID:27366189

  15. Ramsay Hunt Syndrome Associated with Central Nervous System Involvement in an Adult

    PubMed Central

    Chan, Tommy L. H.; Cartagena, Ana M.; Bombassaro, Anne Marie; Hosseini-Moghaddam, Seyed M.

    2016-01-01

    Ramsay Hunt syndrome associated with varicella zoster virus reactivation affecting the central nervous system is rare. We describe a 55-year-old diabetic female who presented with gait ataxia, right peripheral facial palsy, and painful vesicular lesions involving her right ear. Later, she developed dysmetria, fluctuating diplopia, and dysarthria. Varicella zoster virus was detected in the cerebrospinal fluid by polymerase chain reaction. She was diagnosed with Ramsay Hunt syndrome associated with spread to the central nervous system. Her facial palsy completely resolved within 48 hours of treatment with intravenous acyclovir 10 mg/kg every 8 hours. However, cerebellar symptoms did not improve until a tapering course of steroid therapy was initiated. PMID:27366189

  16. The Effects of Tai Chi in Centrally Obese Adults with Depression Symptoms

    PubMed Central

    Liu, Xin; Kostner, Karam; Crompton, David; Williams, Gail; Brown, Wendy J.; Lopez, Alan; Xue, Charlie C.; Oei, Tian P.; Byrne, Gerard; Martin, Jennifer H.; Whiteford, Harvey

    2015-01-01

    This study examined the effects of Tai Chi, a low-impact mind-body movement therapy, on severity of depression, anxiety, and stress symptoms in centrally obese people with elevated depression symptoms. In total, 213 participants were randomized to a 24-week Tai Chi intervention program or a wait-list control group. Assessments were conducted at baseline and 12 and 24 weeks. Outcomes were severity of depression, anxiety, and stress symptoms, leg strength, central obesity, and other measures of metabolic symptom. There were statistically significant between-group differences in favor of the Tai Chi group in depression (mean difference = −5.6 units, P < 0.001), anxiety (−2.3 units, P < 0.01), and stress (−3.6 units, P < 0.001) symptom scores and leg strength (1.1 units, P < 0.001) at 12 weeks. These changes were further improved or maintained in the Tai Chi group relative to the control group during the second 12 weeks of follow-up. Tai Chi appears to be beneficial for reducing severity of depression, anxiety, and stress and leg strength in centrally obese people with depression symptoms. More studies with longer follow-up are needed to confirm the findings. This trial is registered with ACTRN12613000010796. PMID:25688280

  17. The effects of tai chi in centrally obese adults with depression symptoms.

    PubMed

    Liu, Xin; Vitetta, Luis; Kostner, Karam; Crompton, David; Williams, Gail; Brown, Wendy J; Lopez, Alan; Xue, Charlie C; Oei, Tian P; Byrne, Gerard; Martin, Jennifer H; Whiteford, Harvey

    2015-01-01

    This study examined the effects of Tai Chi, a low-impact mind-body movement therapy, on severity of depression, anxiety, and stress symptoms in centrally obese people with elevated depression symptoms. In total, 213 participants were randomized to a 24-week Tai Chi intervention program or a wait-list control group. Assessments were conducted at baseline and 12 and 24 weeks. Outcomes were severity of depression, anxiety, and stress symptoms, leg strength, central obesity, and other measures of metabolic symptom. There were statistically significant between-group differences in favor of the Tai Chi group in depression (mean difference = -5.6 units, P < 0.001), anxiety (-2.3 units, P < 0.01), and stress (-3.6 units, P < 0.001) symptom scores and leg strength (1.1 units, P < 0.001) at 12 weeks. These changes were further improved or maintained in the Tai Chi group relative to the control group during the second 12 weeks of follow-up. Tai Chi appears to be beneficial for reducing severity of depression, anxiety, and stress and leg strength in centrally obese people with depression symptoms. More studies with longer follow-up are needed to confirm the findings. This trial is registered with ACTRN12613000010796. PMID:25688280

  18. Airborne particles of the california central valley alter the lungs of healthy adult rats.

    PubMed Central

    Smith, Kevin R; Kim, Seongheon; Recendez, Julian J; Teague, Stephen V; Ménache, Margaret G; Grubbs, David E; Sioutas, Constantinos; Pinkerton, Kent E

    2003-01-01

    Epidemiologic studies have shown that airborne particulate matter (PM) with a mass median aerodynamic diameter < 10 microm (PM10) is associated with an increase in respiratory-related disease. However, there is a growing consensus that particles < 2.5 microm (PM2.5), including many in the ultrafine (< 0.1 microm) size range, may elicit greater adverse effects. PM is a complex mixture of organic and inorganic compounds; however, those components or properties responsible for biologic effects on the respiratory system have yet to be determined. During the fall and winter of 2000-2001, healthy adult Sprague-Dawley rats were exposed in six separate experiments to filtered air or combined fine (PM2.5) and ultrafine portions of ambient PM in Fresno, California, enhanced approximately 20-fold above outdoor levels. The intent of these studies was to determine if concentrated fine/ultrafine fractions of PM are cytotoxic and/or proinflammatory in the lungs of healthy adult rats. Exposures were for 4 hr/day for 3 consecutive days. The mean mass concentration of particles ranged from 190 to 847 microg/m3. PM was enriched primarily with ammonium nitrate, organic and elemental carbon, and metals. Viability of cells recovered by bronchoalveolar lavage (BAL) from rats exposed to concentrated PM was significantly decreased during 4 of 6 weeks, compared with rats exposed to filtered air (p< 0.05). Total numbers of BAL cells were increased during 1 week, and neutrophil numbers were increased during 2 weeks. These observations strongly suggest exposure to enhanced concentrations of ambient fine/ultrafine particles in Fresno is associated with mild, but significant, cellular effects in the lungs of healthy adult rats. PMID:12782490

  19. Perinatal thiamine restriction affects central GABA and glutamate concentrations and motor behavior of adult rat offspring.

    PubMed

    Ferreira-Vieira, Talita Hélen; de Freitas-Silva, Danielle Marra; Ribeiro, Andrea Frozino; Pereira, Sílvia Rejane Castanheira; Ribeiro, Ângela Maria

    2016-03-23

    The purposes of the present study were to investigate the effects of perinatal thiamine deficiency, from the 11th day of gestation until the 5th day of lactation, on motor behavior and neurochemical parameters in adult rat offspring, using 3-month-old, adult, male Wistar rats. All rats were submitted to motor tests, using the rotarod and paw print tasks. After behavioral tests, their thalamus, cerebellum and spinal cord were dissected for glutamate and GABA quantifications by high performance liquid chromatography. The thiamine-restricted mothers (RM) group showed a significant reduction of time spent on the rotarod at 25 rpm and an increase in hind-base width. A significant decrease of glutamate concentration in the cerebellum and an increase of GABA concentrations in the thalamus were also observed. For the offspring from control mothers (CM) group there were significant correlations between thalamic GABA concentrations and both rotarod performance and average hind-base width. In addition, for rats from the RM group a significant correlation between stride length and cerebellar GABA concentration was found. These results show that the deficiency of thiamine during an early developmental period affects certain motor behavior parameters and GABA and glutamate levels in specific brain areas. Hence, a thiamine deficiency episode during an early developmental period can induce motor impairments and excitatory and inhibitory neurotransmitter changes that are persistent and detectable in later periods of life. PMID:26836141

  20. Lineage mapping identifies molecular and architectural similarities between the larval and adult Drosophila central nervous system

    PubMed Central

    Lacin, Haluk; Truman, James W

    2016-01-01

    Neurogenesis in Drosophila occurs in two phases, embryonic and post-embryonic, in which the same set of neuroblasts give rise to the distinct larval and adult nervous systems, respectively. Here, we identified the embryonic neuroblast origin of the adult neuronal lineages in the ventral nervous system via lineage-specific GAL4 lines and molecular markers. Our lineage mapping revealed that neurons born late in the embryonic phase show axonal morphology and transcription factor profiles that are similar to the neurons born post-embryonically from the same neuroblast. Moreover, we identified three thorax-specific neuroblasts not previously characterized and show that HOX genes confine them to the thoracic segments. Two of these, NB2-3 and NB3-4, generate leg motor neurons. The other neuroblast is novel and appears to have arisen recently during insect evolution. Our findings provide a comprehensive view of neurogenesis and show how proliferation of individual neuroblasts is dictated by temporal and spatial cues. DOI: http://dx.doi.org/10.7554/eLife.13399.001 PMID:26975248

  1. Predictive equations for central obesity via anthropometrics, stereovision imaging, and MRI in adults

    PubMed Central

    Lee, Jane J; Freeland-Graves, Jeanne H; Pepper, M Reese; Yao, Ming; Xu, Bugao

    2013-01-01

    Objective Abdominal visceral adiposity is related to risks for insulin resistance and metabolic perturbations. Magnetic resonance imaging (MRI) and computed tomography are advanced instruments that quantify abdominal adiposity; yet field use is constrained by their bulkiness and costliness. The purpose of this study is to develop prediction equations for total abdominal, subcutaneous, and visceral adiposity via anthropometrics, stereovision body imaging (SBI), and MRI. Design and Methods Participants (67 men and 55 women) were measured for anthropometrics, and abdominal adiposity volumes evaluated by MRI umbilicus scans. Body circumferences and central obesity were obtained via SBI. Prediction models were developed via multiple linear regression analysis, utilizing body measurements and demographics as independent predictors, and abdominal adiposity as a dependent variable. Cross-validation was performed by the data-splitting method. Results The final total abdominal adiposity prediction equation was –470.28+7.10waist circumference–91.01gender+5.74sagittal diameter (R²=89.9%); subcutaneous adiposity was –172.37+8.57waist circumference–62.65gender–450.16stereovision waist-to-hip ratio (R²=90.4%); and visceral adiposity was –96.76+11.48central obesity depth–5.09 central obesity width+204.74stereovision waist-to-hip ratio–18.59gender (R²=71.7%). R² significantly improved for predicting visceral fat when SBI variables were included, but not for total abdominal or subcutaneous adiposity. Conclusions SBI is effective for predicting visceral adiposity and the prediction equations derived from SBI measurements can assess obesity. PMID:23613161

  2. Relation of adult size to movements and distribution of smallmouth bass in a central Maine Lake

    USGS Publications Warehouse

    Cole, M.B.; Moring, J.R.

    1997-01-01

    Forty-four smallmouth bass Micropterus dolomieu of three size-classes were radiotracked in Green Lake, Maine, during summer 1993 (10 June-1 September) to determine whether adult size influenced distribution and movement. Large smallmouth bass (>406 mm) used deep water (>8 m) more often than did small (248-279 mm) or medium-sized (305-356 mm) smallmouth bass during the late summer (15 July-1 September). Large smallmouth bass also were found at middepths (4-8 m) significantly more often than were small individuals during late summer. Small fish used cover more frequently than large ones during early summer (10 June-13 July). Both small and medium-sized individuals were associated with cover more frequently than large smallmouth bass were during the late summer. Small smallmouth bass exhibited significantly smaller summer total ranges than did large individuals, and mean active displacement differed among all three size-classes.

  3. Age-related changes in reservoir and excess components of central aortic pressure in asymptomatic adults.

    PubMed

    Bia, Daniel; Cymberknop, Leandro; Zócalo, Yanina; Farro, Ignacio; Torrado, Juan; Farro, Federico; Pessana, Franco; Armentano, Ricardo L

    2011-01-01

    Study of humans aging has presented difficulties in separating the aging process from concomitant disease and/or in defining normality and abnormality during its development. In accordance with this, aging associates structural and functional changes evidenced in variations in vascular parameters witch suffer alterations during atherosclerosis and have been proposed as early markers of the disease. The absence of adequate tools to differentiate the expected (normal) vascular changes due to aging from those related with a vascular disease is not a minor issue. For an individual, an early diagnosis of a vascular disease should be as important as the diagnosis of a healthy vascular aging. Recent studies have proposed that the capacitive or reservoir function of the aorta and large elastic arteries plays a major role in determining the pulse wave morphology. The arterial pressure waveform can be explained in terms of a reservoir pressure, related to the arterial system compliance, and an "excess" or wave-related pressure, associated with the traveling waves. The aim of this study was to evaluate, by means of a mathematical approach, age-related changes in measured, reservoir and excess central aortic pressure in order to determine if age-related changes are concentrated in particular decades of life. Central aortic pressure waveform was non-invasively obtained in healthy subjects (age range: 20-69 years old). Age-related profiles in measured, reservoir and excess pressure were calculated. PMID:22255816

  4. Perception and Attitude of a Rural Community Regarding Adult Blindness in North Central Nigeria

    PubMed Central

    Olatunji, Victoria A.; Adepoju, Feyi G.; Owoeye, Joshua F. A.

    2015-01-01

    Aim: To determine the perception and attitudes of a rural community regarding the etiology, prevention, and treatment of blindness in adults. Methods: A cross-sectional, descriptive study was performed in a rural community in Kwara State, Nigeria using semi-structured questionnaire. All adults aged 40 years or older who were residents for a minimum of 6 months in the community were included. Data were collected on patient demographics, knowledge, attitude, perception, and use of the eye care facility. Results: A total of 290 participants were interviewed. The male-to-female ratio was 1:2. Consumption of certain types of food was an important cause of blindness as perceived by 57.9% of the respondents, followed by supernatural forces (41.7%) and aging (19%). Sixty percent of respondents thought blindness could be prevented. Age (P = 0.04) and level of education (P =0.003) significantly affected the beliefs on the prevention of blindness. Most respondents (79.3%) preferred orthodox eye care, but only 65% would accept surgical intervention if required. The level of education significantly affected the acceptance of surgery (P = 0.04). Reasons for refusing surgery were, fear (64%), previous poor outcomes in acquaintances (31%), belief that surgery is not required (3%), and cost (2%). About 65% used one form of traditional eye medication or the other. Over half (56.6%) believed that spectacles could cure all causes of blindness. Of those who had ocular complaints, 57.1% used orthodox care without combining with either traditional or spiritual remedies. Conclusion: This rural Nigerian community had some beliefs that were consistent with modern knowledge. However, the overall knowledge, attitude, and perceptions of this community need to be redirected to favor the eradication of avoidable blindness. Although an eye care facility was available, use by the community was suboptimal. Age and the level of education affected their overall perception and attitudes. PMID:26692726

  5. Birth weight modifies the association between central-nervous-system gene variation and adult body mass index

    PubMed Central

    Ruiz-Narváez, Edward A.; Haddad, Stephen A.; Rosenberg, Lynn; Palmer, Julie R.

    2015-01-01

    Genome wide association studies (GWAS) have identified approximately 100 loci associated with body mass index (BMI). Persons with low birth-weight have an increased risk of metabolic disorders. We postulate that normal mechanisms of body weight regulation are disrupted in subjects with low birth-weight. The present analyses included 2215 African American women from the Black Women’s Health Study, and were based on genotype data on twenty BMI-associated loci and self-reported data on birth-weight, weight at age 18, and adult weight. We used general linear models to assess the association of individual SNPs with BMI at age 18 and later in adulthood within strata of birth-weight (above and below the median, 3200 g). Three SNPs (rs1320330 near TMEM18, rs261967 near PCSK1, and rs17817964 in FTO), and a genetic score combining these three variants, showed significant interactions with birth-weight in relation to BMI. Among women with birth-weight <3200 g, there was an inverse association between genetic score and BMI; beta-coefficient = −0.045 (95% CI −0.104, 0.013) for BMI at age 18, and −0.055 (95% CI −0.112, 0.002) for adult BMI. Among women with birth-weight ≥3,200 g, genetic score was positively associated with BMI: beta-coefficient = 0.110 (95% CI 0.051, 0.169) for BMI at age 18 (P for interaction = 0.0002), and 0.112 (95% CI 0.054, 0.170) for adult BMI (P for interaction < 0.0001). Because TMEM18, PCSK1, and FTO are highly expressed in the central nervous system (CNS), our results suggest that low birth-weight may disrupt mechanisms of CNS body weight regulation. PMID:26582267

  6. Effects of low-energy He-Ne laser irradiation on posttraumatic degeneration of adult rabbit optic nerve

    SciTech Connect

    Schwartz, M.; Doron, A.; Erlich, M.; Lavie, V.; Benbasat, S.; Belkin, M.; Rochkind, S.

    1987-01-01

    Axons of the mammalian peripheral and central nervous systems degenerate after nerve injury. We have recently found that He-Ne laser irradiation may prevent some of the consequences of the injury in peripheral nerves of mammals. In the present study, the efficacy of the laser in treating injured neurons of the mammalian CNS was tested. Optic nerves of adult rabbits were exposed daily for 8-14 days to He-Ne laser irradiation (14 min, 15 mW) through the overlying muscles and skin. As a result of this treatment, the injured nerves maintained their histological integrity, which is invariably lost in injured mammalian CNS neurons.

  7. Pulmonary Langerhans Cell Histiocytosis in an Adult Male Presenting with Central Diabetes Insipidus and Diabetes Mellitus: A Case Report

    PubMed Central

    Choi, Yeun Seoung; Lim, Jung Soo; Kwon, Woocheol; Jung, Soon-Hee; Park, Il Hwan; Lee, Myoung Kyu; Lee, Won Yeon; Yong, Suk Joong; Lee, Seok Jeong; Jung, Ye-Ryung; Choi, Jiwon; Choi, Ji Sun; Jeong, Joon Taek; Yoo, Jin Sae

    2015-01-01

    Pulmonary Langerhans cell histiocytosis is an uncommon diffuse cystic lung disease in adults. In rare cases, it can involve extrapulmonary organs and lead to endocrine abnormalities such as central diabetes insipidus. A 42-year-old man presented with polyphagia and polydipsia, as well as a dry cough and dyspnea on exertion. Magnetic resonance imaging of the hypothalamic-pituitary system failed to show the posterior pituitary, which is a typical finding in patients with central diabetes insipidus. This condition was confirmed by a water deprivation test, and the patient was also found to have type 2 diabetes mellitus. Computed tomographic scanning of the lungs revealed multiple, irregularly shaped cystic lesions and small nodules bilaterally, with sparing of the costophrenic angles. Lung biopsy through video-assisted thoracoscopic surgery revealed pulmonary Langerhans cell histiocytosis. On a follow-up visit, only 1 year after the patient had quit smoking, clinical and radiological improvement was significant. Here, we report an uncommon case of pulmonary Langerhans cell histiocytosis that simultaneously presented with diabetes insipidus and diabetes mellitus. PMID:26508947

  8. Pulmonary Langerhans Cell Histiocytosis in an Adult Male Presenting with Central Diabetes Insipidus and Diabetes Mellitus: A Case Report.

    PubMed

    Choi, Yeun Seoung; Lim, Jung Soo; Kwon, Woocheol; Jung, Soon-Hee; Park, Il Hwan; Lee, Myoung Kyu; Lee, Won Yeon; Yong, Suk Joong; Lee, Seok Jeong; Jung, Ye-Ryung; Choi, Jiwon; Choi, Ji Sun; Jeong, Joon Taek; Yoo, Jin Sae; Kim, Sang-Ha

    2015-10-01

    Pulmonary Langerhans cell histiocytosis is an uncommon diffuse cystic lung disease in adults. In rare cases, it can involve extrapulmonary organs and lead to endocrine abnormalities such as central diabetes insipidus. A 42-year-old man presented with polyphagia and polydipsia, as well as a dry cough and dyspnea on exertion. Magnetic resonance imaging of the hypothalamic-pituitary system failed to show the posterior pituitary, which is a typical finding in patients with central diabetes insipidus. This condition was confirmed by a water deprivation test, and the patient was also found to have type 2 diabetes mellitus. Computed tomographic scanning of the lungs revealed multiple, irregularly shaped cystic lesions and small nodules bilaterally, with sparing of the costophrenic angles. Lung biopsy through video-assisted thoracoscopic surgery revealed pulmonary Langerhans cell histiocytosis. On a follow-up visit, only 1 year after the patient had quit smoking, clinical and radiological improvement was significant. Here, we report an uncommon case of pulmonary Langerhans cell histiocytosis that simultaneously presented with diabetes insipidus and diabetes mellitus. PMID:26508947

  9. Ontogenetic development of the mammalian circadian system.

    PubMed

    Weinert, Dietmar

    2005-01-01

    This review summarizes the current knowledge about the ontogenetic development of the circadian system in mammals. The developmental changes of overt rhythms are discussed, although the main focus of the review is the underlying neuronal and molecular mechanisms. In addition, the review describes ontogenetic development, not only as a process of morpho-functional maturation. The need of repeated adaptations and readaptations due to changing developmental stage and environmental conditions is also considered. The review analyzes mainly rodent data, obtained from the literature and from the author's own studies. Results from other species, including humans, are presented to demonstrate common features and species-dependent differences. The review first describes the development of the suprachiasmatic nuclei as the central pacemaker system and shows that intrinsic circadian rhythms are already generated in the mammalian fetus. As in adult organisms, the period length is different from 24 h and needs continuous correction by environmental periodicities, or zeitgebers. The investigation of the ontogenetic development of the mechanisms of entrainment reveals that, at prenatal and early postnatal stages, non-photic cues deriving from the mother are effective. Light-dark entrainment develops later. At a certain age, both photic and non-photic zeitgebers may act in parallel, even though the respective time information is 12 h out of phase. That leads to a temporary internal desynchronization. Because rhythmic information needs to be transferred to effector organs, the corresponding neural and humoral signalling pathways are also briefly described. Finally, to be able to transform a rhythmic signal into an overt rhythm, the corresponding effector organs must be functionally mature. As many of these organs are able to generate their own intrinsic rhythms, another aspect of the review is dedicated to the development of peripheral oscillators and mechanisms of their entrainment

  10. Effect of omega-3 polyunsaturated fatty acid supplementation on central arterial stiffness and arterial wave reflections in young and older healthy adults

    PubMed Central

    Monahan, Kevin D; Feehan, Robert P; Blaha, Cheryl; McLaughlin, Daniel J

    2015-01-01

    Increased central arterial stiffness and enhanced arterial wave reflections may contribute to increased risk of cardiovascular disease development with advancing age. Omega-3 polyunsaturated fatty acid (n-3) ingestion may reduce cardiovascular risk via favorable effects exerted on arterial structure and function. We determined the effects of n-3 supplementation (4 g/day for 12 weeks) on important measures of central arterial stiffness (carotid-femoral pulse wave velocity; PWV) and arterial wave reflection (central augmentation index) in young (n = 12; 25 ± 1-year-old, mean ± SE) and older (n = 12; 66 ± 2) healthy adults. We hypothesized that n-3 supplementation would decrease carotid-femoral PWV and central augmentation index in older adults. Our results indicate that carotid-femoral PWV and central augmentation index were greater in older (988 ± 65 cm/sec and 33 ± 2%) than in young adults (656 ± 16 cm/sec and 3 ± 4%: both P < 0.05 compared to older) before the intervention (Pre). N-3 supplementation decreased carotid-femoral PWV in older (Δ-9 ± 2% Precompared to Post; P < 0.05), but not young adults (Δ2 ± 3%). Central augmentation index was unchanged by n-3 supplementation in young (3 ± 4 vs. 0 ± 4% for Pre and Post, respectively) and older adults (33 ± 2 vs. 35 ± 3%). Arterial blood pressure at rest, although increased with age, was not altered by n-3 supplementation in young or older adults. Collectively, these data indicate that 12 weeks of daily n-3 supplementation decreases an important measure of central arterial stiffness (carotid-femoral PWV) in older, but not young healthy adults. The mechanism underlying decreased central arterial stiffness with n-3 supplementation is unknown, but appears to be independent of effects on arterial blood pressure or arterial wave reflections. PMID:26109192

  11. The role of repulsive guidance molecules in the embryonic and adult vertebrate central nervous system

    PubMed Central

    Mueller, Bernhard K; Yamashita, Toshihide; Schaffar, Gregor; Mueller, Reinhold

    2006-01-01

    During the development of the nervous system, outgrowing axons often have to travel long distances to reach their target neurons. In this process, outgrowing neurites tipped with motile growth cones rely on guidance cues present in their local environment. These cues are detected by specific receptors expressed on growth cones and neurites and influence the trajectory of the growing fibres. Neurite growth, guidance, target innervation and synapse formation and maturation are the processes that occur predominantly but not exclusively during embryonic or early post-natal development in vertebrates. As a result, a functional neural network is established, which is usually remarkably stable. However, the stability of the neural network in higher vertebrates comes at an expensive price, i.e. the loss of any significant ability to regenerate injured or damaged neuronal connections in their central nervous system (CNS). Most importantly, neurite growth inhibitors prevent any regenerative growth of injured nerve fibres. Some of these inhibitors are associated with CNS myelin, others are found at the lesion site and in the scar tissue. Traumatic injuries in brain and spinal cord of mammals induce upregulation of embryonic inhibitory or repulsive guidance cues and their receptors on the neurites. An example for embryonic repulsive directional cues re-expressed at lesion sites in both the rat and human CNS is provided with repulsive guidance molecules, a new family of directional guidance cues. PMID:16939972

  12. Adult survivorship of the dengue mosquito Aedes aegypti varies seasonally in central Vietnam.

    PubMed

    Hugo, Leon E; Jeffery, Jason A L; Trewin, Brendan J; Wockner, Leesa F; Nguyen, Thi Yen; Nguyen, Hoang Le; Nghia, Le Trung; Hine, Emma; Ryan, Peter A; Kay, Brian H

    2014-02-01

    The survival characteristics of the mosquito Aedes aegypti affect transmission rates of dengue because transmission requires infected mosquitoes to survive long enough for the virus to infect the salivary glands. Mosquito survival is assumed to be high in tropical, dengue endemic, countries like Vietnam. However, the survival rates of wild populations of mosquitoes are seldom measured due the difficulty of predicting mosquito age. Hon Mieu Island in central Vietnam is the site of a pilot release of Ae. aegypti infected with a strain of Wolbachia pipientis bacteria (wMelPop) that induces virus interference and mosquito life-shortening. We used the most accurate mosquito age grading approach, transcriptional profiling, to establish the survival patterns of the mosquito population from the population age structure. Furthermore, estimations were validated on mosquitoes released into a large semi-field environment consisting of an enclosed house, garden and yard to incorporate natural environmental variability. Mosquito survival was highest during the dry/cool (January-April) and dry/hot (May-August) seasons, when 92 and 64% of Hon Mieu mosquitoes had survived to an age that they were able to transmit dengue (12 d), respectively. This was reduced to 29% during the wet/cool season from September to December. The presence of Ae. aegypti older than 12 d during each season is likely to facilitate the observed continuity of dengue transmission in the region. We provide season specific Ae. aegypti survival models for improved dengue epidemiology and evaluation of mosquito control strategies that aim to reduce mosquito survival to break the dengue transmission cycle. PMID:24551251

  13. Landscape Analysis of Adult Codling Moth (Lepidoptera: Tortricidae) Distribution and Dispersal within Typical Agroecosystems Dominated by Apple Production in Central Chile

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We analyzed the spatial distribution and dispersal of codling moth, Cydia pomonella (L.), adults within two heterogeneous agro-ecosystems typical of central Chile; commercial apple, Malus domestica Borkhausen, orchards surrounded by various unmanaged host plants. Both a geostatistical analysis of ca...

  14. Overwintering of Uranotaenia Unguiculata Adult Females in Central Europe: A Possible Way of Persistence of the Putative New Lineage of West Nile Virus?

    PubMed

    Rudolf, Ivo; Šebesta, Oldřich; Straková, Petra; Betášová, Lenka; Blažejová, Hana; VEnclíková, Kristýna; Seidel, Bernhard; Tóth, Sandor; Hubálek, Zdeněk; Schaffner, Francis

    2015-12-01

    We report the overwintering of Uranotaenia unguiculata adult females in Central Europe (Czech Republic, Hungary, Austria). This finding suggests a potential mode of winter persistence of putative novel lineage of West Nile virus in the temperate regions of Europe. PMID:26675459

  15. Utilization of central nervous system resources for preparation and performance of complex walking tasks in older adults

    PubMed Central

    Clark, David J.; Rose, Dorian K.; Ring, Sarah A.; Porges, Eric C.

    2014-01-01

    Introduction: Walking in the home and community often involves performance of complex walking tasks. Understanding the control of such tasks is crucial to preserving independence and quality of life in older adults. However, very little research has been conducted in this area. Here, we assess the extent to which two measures of central nervous system (CNS) activity are responsive to the challenges posed by preparation and performance of complex walking tasks. Prefrontal cortical activity was measured by functional near-infrared spectroscopy (fNIRS) and sympathetic nervous system arousal was measured by skin conductance level (SCL). Materials and methods: Sixteen older men and women (age: 77.2 ± 5.6 years) with mild mobility deficits participated in this study. Participants walked at their preferred speed without distractions along an unobstructed, well-lit course (control task) and also walked on the same course under five separate challenging conditions: performing a cognitive verbal fluency task (verbal task), dim lighting (dim task), carrying a tray (carry task), negotiating obstacles (obstacles task) and wearing a weighted vest (vest task). Mean prefrontal activation and SCL were calculated during the preparation and performance phases of each task. Gait spatiotemporal measurements were acquired by an instrumented gait mat. Results: Prefrontal cortical activity and SCL were elevated during the preparation phase of complex walking tasks relative to the control task. During the performance phase, prefrontal activity remained elevated to a similar level as during task preparation. In contrast, SCL continued to increase beyond the level observed during task preparation. A larger increase in prefrontal activity was found to be linked to preserved quality of gait during complex walking tasks. Discussion: These findings indicate that availability and utilization of CNS resources are important for optimizing performance of complex walking tasks in older adults. PMID

  16. Chronic prenatal ethanol exposure alters expression of central and peripheral insulin signaling molecules in adult guinea pig offspring.

    PubMed

    Dobson, Christine C; Thevasundaram, Kersh; Mongillo, Daniel L; Winterborn, Andrew; Holloway, Alison C; Brien, James F; Reynolds, James N

    2014-11-01

    Maternal ethanol consumption during pregnancy can produce a range of teratogenic outcomes in offspring. The mechanism of ethanol teratogenicity is multi-faceted, but may involve alterations in insulin and insulin-like growth factor (IGF) signaling pathways. These pathways are not only important for metabolism, but are also critically involved in neuronal survival and plasticity, and they can be altered by chronic prenatal ethanol exposure (CPEE). The objective of this study was to test the hypothesis that CPEE alters expression of insulin and IGF signaling molecules in the prefrontal cortex and liver of adult guinea pig offspring. Pregnant Dunkin-Hartley-strain guinea pigs received ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding (nutritional control) throughout gestation. Fasting blood glucose concentration was measured in male and female offspring at postnatal day 150-200, followed by euthanasia, collection of prefrontal cortex and liver, and RNA extraction. IGF-1, IGF-1 receptor (IGF-1R), IGF-2, IGF-2 receptor (IGF-2R), insulin receptor substrate (IRS)-1, IRS-2, and insulin receptor (INSR) mRNA expression levels were measured in tissues using quantitative real-time PCR. The mean maternal blood ethanol concentration was 281 ± 15 mg/dL at 1 h after the second divided dose of ethanol on GD 57. CPEE resulted in increased liver weight in adult offspring, but produced no difference in fasting blood glucose concentration compared with nutritional control. In the liver, CPEE decreased mRNA expression of IGF-1, IGF-1R, and IGF-2, and increased IRS-2 mRNA expression in male offspring only compared with nutritional control. Female CPEE offspring had decreased INSR hepatic mRNA expression compared with male CPEE offspring. In the prefrontal cortex, IRS-2 mRNA expression was increased in CPEE offspring compared with nutritional control. The data demonstrate that CPEE alters both central and peripheral expression of insulin and IGF signaling

  17. Perceptions of food-insecure HIV-positive adults participating in a food supplementation program in central Kenya.

    PubMed

    Ndirangu, Murugi; Sztam, Kevin; Sheriff, Muhsin; Hawken, Mark; Arpadi, Stephen; Rashid, Juma; Deckelbaum, Richard; El-Sadr, Wafaa

    2014-11-01

    Malnutrition coexists with HIV in sub-Saharan Africa. Food supplementation is recommended for food-insecure, HIV-positive individuals. This study was part of a larger six-month food supplementation program for adults initiating antiretroviral therapy (ART) in central Kenya. We conducted 10 focus group interviews with program participants to examine the perceptions of participants regarding the food supplementation program. Focus group transcripts were analyzed for themes and six were identified. These were perception of food insecurity and the health of the participants, the benefits of participating, use of the food, coping strategies after the program ended, suggestions for improving the program, and sustainability of the benefits. Participants perceived that the food improved their health and ART adherence, and reduced stigma. The improvements were not always sustained. Sharing with people beyond the immediate family was very common, depleting the food available to the participants. Interventions with sustainable effects for food-insecure, HIV-positive individuals and their families are needed. PMID:25418241

  18. Pathology, physiologic parameters, tissue contaminants, and tissue thiamine in morbid and healthy central Florida adult American alligators (Alligator mississippiensis).

    PubMed

    Honeyfield, Dale C; Ross, J Perran; Carbonneau, Dwayne A; Terrell, Scott P; Woodward, Allan R; Schoeb, Trenton R; Perceval, H Franklin; Hinterkopf, Joy P

    2008-04-01

    An investigation of adult alligator (Alligator mississippiensis) mortalities in Lake Griffin, central Florida, was conducted from 1998-2004. Alligator mortality was highest in the months of April and May and annual death count peaked in 2000. Bacterial pathogens, heavy metals, and pesticides were not linked with the mortalities. Blood chemistry did not point to any clinical diagnosis, although differences between impaired and normal animals were noted. Captured alligators with signs of neurologic impairment displayed unresponsive and uncoordinated behavior. Three of 21 impaired Lake Griffin alligators were found to have neural lesions characteristic of thiamine deficiency in the telencephalon, particularly the dorsal ventricular ridge. In some cases, lesions were found in the thalamus, and parts of the midbrain. Liver and muscle tissue concentrations of thiamine (vitamin B(1)) were lowest in impaired Lake Griffin alligators when compared to unimpaired alligators or to alligators from Lake Woodruff. The consumption of thiaminase-positive gizzard shad (Dorosoma cepedianum) is thought to have been the cause of the low tissue thiamine and resulting mortalities. PMID:18436661

  19. Pathology, physiologic parameters, tissue contaminants, and tissue thiamine in morbid and healthy central Florida adult American alligators (Alligator mississippiensis)

    USGS Publications Warehouse

    Honeyfield, D.C.; Ross, J.P.; Carbonneau, D.A.; Terrell, S.P.; Woodward, A.R.; Schoeb, T.R.; Perceval, H.F.; Hinterkopf, J.P.

    2008-01-01

    An investigation of adult alligator (Alligator mississippiensis) mortalities in Lake Griffin, central Florida, was conducted from 1998-2004. Alligator mortality was highest in the months of April and May and annual death count peaked in 2000. Bacterial pathogens, heavy metals, and pesticides were not linked with the mortalities. Blood chemistry did not point to any clinical diagnosis, although differences between impaired and normal animals were noted. Captured alligators with signs of neurologic impairment displayed unresponsive and uncoordinated behavior. Three of 21 impaired Lake Griffin alligators were found to have neural lesions characteristic of thiamine deficiency in the telencephalon, particularly the dorsal ventricular ridge. In some cases, lesions were found in the thalamus, and parts of the midbrain. Liver and muscle tissue concentrations of thiamine (vitamin B"1) were lowest in impaired Lake Griffin alligators when compared to unimpaired alligators or to alligators from Lake Woodruff. The consumption of thiaminase-positive gizzard shad (Dorosoma cepedianum) is thought to have been the cause of the low tissue thiamine and resulting mortalities. ?? Wildlife Disease Association 2008.

  20. Adult T-Cell Lymphoma/Leukemia Presenting as Isolated Central Nervous System T-Cell Lymphoma

    PubMed Central

    Ma, Wei-Li; Li, Chi-Cheng; Yu, Shan-Chi; Tien, Hwei-Fang

    2014-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is a T-cell neoplasm, associated with infection by the retrovirus human T-lymphotropic virus type 1 (HTLV-1). Central nervous system (CNS) involved by ATLL is often occurred in advanced disease, such as acute and lymphomatous variants. On the other hand, isolated CNS lymphoma is rare. We repot a 50-year-old woman who presented with multiple infiltrative brain lesions on the magnetic resonance (MR) imaging. Results of initial biopsy of brain tumor indicated CNS vasculitis. The patient received one course of high-dose methotrexate and MR imaging of brain revealed remission of infiltrative lesions. Two years later, new brain lesions were detected. Histopathologic examination of specimens via craniotomy revealed T-cell lymphoma. The patient responded poorly to subsequent chemotherapy, and salvage whole-brain irradiation was performed. Six months later, the patient had hepatosplenomegaly, hypercalcemia, and multiple lymphocytes with a cloverleaf appearance in circulation. Results of flow cytometry analysis of peripheral blood indicated ATLL and antibodies to human T-lymphotropic virus type 1 (HTLV-1) were detected. Clinicians should screen HTLV-1 infection when patients are diagnosed with peripheral T-cell lymphoma. Combined antiviral therapy and intensive chemotherapy may improve the outcomes of ATLL. PMID:25587470

  1. Adult T-cell lymphoma/leukemia presenting as isolated central nervous system T-cell lymphoma.

    PubMed

    Ma, Wei-Li; Li, Chi-Cheng; Yu, Shan-Chi; Tien, Hwei-Fang

    2014-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is a T-cell neoplasm, associated with infection by the retrovirus human T-lymphotropic virus type 1 (HTLV-1). Central nervous system (CNS) involved by ATLL is often occurred in advanced disease, such as acute and lymphomatous variants. On the other hand, isolated CNS lymphoma is rare. We repot a 50-year-old woman who presented with multiple infiltrative brain lesions on the magnetic resonance (MR) imaging. Results of initial biopsy of brain tumor indicated CNS vasculitis. The patient received one course of high-dose methotrexate and MR imaging of brain revealed remission of infiltrative lesions. Two years later, new brain lesions were detected. Histopathologic examination of specimens via craniotomy revealed T-cell lymphoma. The patient responded poorly to subsequent chemotherapy, and salvage whole-brain irradiation was performed. Six months later, the patient had hepatosplenomegaly, hypercalcemia, and multiple lymphocytes with a cloverleaf appearance in circulation. Results of flow cytometry analysis of peripheral blood indicated ATLL and antibodies to human T-lymphotropic virus type 1 (HTLV-1) were detected. Clinicians should screen HTLV-1 infection when patients are diagnosed with peripheral T-cell lymphoma. Combined antiviral therapy and intensive chemotherapy may improve the outcomes of ATLL. PMID:25587470

  2. Central amygdala lesions inhibit pontine nuclei acoustic reactivity and retard delay eyeblink conditioning acquisition in adult rats.

    PubMed

    Pochiro, Joseph M; Lindquist, Derick H

    2016-06-01

    In delay eyeblink conditioning (EBC) a neutral conditioned stimulus (CS; tone) is repeatedly paired with a mildly aversive unconditioned stimulus (US; periorbital electrical shock). Over training, subjects learn to produce an anticipatory eyeblink conditioned response (CR) during the CS, prior to US onset. While cerebellar synaptic plasticity is necessary for successful EBC, the amygdala is proposed to enhance eyeblink CR acquisition. In the current study, adult Long-Evans rats received bilateral sham or neurotoxic lesions of the central nucleus of the amygdala (CEA) followed by 1 or 4 EBC sessions. Fear-evoked freezing behavior, CS-mediated enhancement of the unconditioned response (UR), and eyeblink CR acquisition were all impaired in the CEA lesion rats relative to sham controls. There were also significantly fewer c-Fos immunoreactive cells in the pontine nuclei (PN)-major relays of acoustic information to the cerebellum-following the first and fourth EBC session in lesion rats. In sham rats, freezing behavior decreased from session 1 to 4, commensurate with nucleus-specific reductions in amygdala Fos+ cell counts. Results suggest delay EBC proceeds through three stages: in stage one the amygdala rapidly excites diffuse fear responses and PN acoustic reactivity, facilitating cerebellar synaptic plasticity and the development of eyeblink CRs in stage two, leading, in stage three, to a diminution or stabilization of conditioned fear responding. PMID:26486933

  3. Adult DRG Stem/Progenitor Cells Generate Pericytes in the Presence of Central Nervous System (CNS) Developmental Cues, and Schwann Cells in Response to CNS Demyelination.

    PubMed

    Vidal, Marie; Maniglier, Madlyne; Deboux, Cyrille; Bachelin, Corinne; Zujovic, Violetta; Baron-Van Evercooren, Anne

    2015-06-01

    It has been proposed that the adult dorsal root ganglia (DRG) harbor neural stem/progenitor cells (NPCs) derived from the neural crest. However, the thorough characterization of their stemness and differentiation plasticity was not addressed. In this study, we investigated adult DRG-NPC stem cell properties overtime, and their fate when ectopically grafted in the central nervous system. We compared them in vitro and in vivo to the well-characterized adult spinal cord-NPCs derived from the same donors. Using micro-dissection and neurosphere cultures, we demonstrate that adult DRG-NPCs have quasi unlimited self-expansion capacities without compromising their tissue specific molecular signature. Moreover, they differentiate into multiple peripheral lineages in vitro. After transplantation, adult DRG-NPCs generate pericytes in the developing forebrain but remyelinating Schwann cells in response to spinal cord demyelination. In addition, we show that axonal and endothelial/astrocytic factors as well astrocytes regulate the fate of adult DRG-NPCs in culture. Although the adult DRG-NPC multipotency is restricted to the neural crest lineage, their dual responsiveness to developmental and lesion cues highlights their impressive adaptive and repair potentials making them valuable targets for regenerative medicine. PMID:25786382

  4. Development of the Mammalian Kidney.

    PubMed

    McMahon, Andrew P

    2016-01-01

    The basic unit of kidney function is the nephron. In the mouse, around 14,000 nephrons form in a 10-day period extending into early neonatal life, while the human fetus forms the adult complement of nephrons in a 32-week period completed prior to birth. This review discusses our current understanding of mammalian nephrogenesis: the contributing cell types and the regulatory processes at play. A conceptual developmental framework has emerged for the mouse kidney. This framework is now guiding studies of human kidney development enabled in part by in vitro systems of pluripotent stem cell-seeded nephrogenesis. A near future goal will be to translate our developmental knowledge-base to the productive engineering of new kidney structures for regenerative medicine. PMID:26969971

  5. Glia in mammalian development and disease.

    PubMed

    Zuchero, J Bradley; Barres, Ben A

    2015-11-15

    Glia account for more than half of the cells in the mammalian nervous system, and the past few decades have witnessed a flood of studies that detail novel functions for glia in nervous system development, plasticity and disease. Here, and in the accompanying poster, we review the origins of glia and discuss their diverse roles during development, in the adult nervous system and in the context of disease. PMID:26577203

  6. Ocular biometry in the adult population in rural central China: a population-based, cross-sectional study

    PubMed Central

    Fu, Ting; Song, Yin-Wei; Chen, Zhi-Qi; He, Jun-Wen; Qiao, Kun; Sun, Xu-Fang; Zhang, Hong; Wang, Jun-Ming

    2015-01-01

    AIM To describe the distribution and determinants of ocular biometric parameters and to ascertain the relative importance of these determinants in a large population of adults in rural central China. METHODS A population-based, cross-sectional study performed in rural central China included 1721 participants aged 40 or more years. Ocular biometrical parameters including axial length (AL), anterior chamber depth (ACD), radius of corneal curvature (K) and horizontal corneal diameter [white-to-white (WTW) distance] were measured using non-contact partial coherence interferometry [intraocular lens (IOL)-Master]. RESULTS Ocular biometric data on 1721 participants with a average age of 57.0±8.7y were analyzed at last. The general mean AL, ACD, mean corneal curvature radius (MCR), WTW were 22.80±1.12, 2.96±0.36, 7.56±0.26 and 11.75±0.40 mm, respectively. The mean values of each parameter in 40 to 49, 50 to 59, 60 to 69, and 70 to 91 years age groups were as follows: AL, 22.77±0.87, 22.76±1.06, 22.89±1.41, 22.92±0.80 mm; ACD, 3.10±0.32, 2.98±0.34, 2.86±0.36, 2.77±0.35 mm; MCR, 7.58±0.25, 7.54±0.26, 7.55±0.26, 7.49±0.28 mm; WTW, 11.79±0.38, 11.75±0.40, 11.72±0.41, 11.67±0.41 mm. The AL, ACD, MCR and WTW were correlated with age and the AL was correlated with height and weight. CONCLUSION Our findings can serve as an important normative reference for multiple purposes and may help to improve the quality of rural eye care. PMID:26309884

  7. Mammalian cardiolipin biosynthesis.

    PubMed

    Mejia, Edgard M; Nguyen, Hieu; Hatch, Grant M

    2014-04-01

    Cardiolipin is a major phospholipid in mitochondria and is involved in the generation of cellular energy in the form of ATP. In mammalian and eukaryotic cells it is synthesized via the cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol phosphate pathway. This brief review will describe some of the more recent studies on mammalian cardiolipin biosynthesis and provide an overview of regulation of cardiolipin biosynthesis. In addition, the important role that this key phospholipid plays in disease processes including heart failure, diabetes, thyroid hormone disease and the genetic disease Barth Syndrome will be discussed. PMID:24144810

  8. Astroglial cells in the central nervous system of the adult brown anole lizard, Anolis sagrei, revealed by intermediate filament immunohistochemistry.

    PubMed

    Lazzari, Maurizio; Franceschini, Valeria

    2005-09-01

    We analyzed the distribution of intermediate filament molecular markers, glial fibrillary acidic protein (GFAP), and vimentin in the brain and spinal cord of the adult brown anole lizard, Anolis sagrei. The GFAP immunoreactivity is strong and the positive structures are basically represented by fibers of different lengths and thicknesses which are arranged in a regular radial pattern throughout the central nervous system. In the brain regions that have a thicker neural wall, the radial orientation is not so evident as in the thinner areas. These fibers emerge from radial ependymoglia (tanycytes) whose cell bodies are generally GFAP-immunopositive. The glial fibers give rise to endfeet that are apposed to the subpial surface and to blood vessel walls. In the spinal cord, the optic tectum and the lateroventral regions of the mesencephalon and medulla oblongata, star-shaped astrocytes coexist with radial structures. Vimentin-immunoreactive structures are absent in the brain and spinal cord. In A. sagrei the immunohistochemical response of the astroglial intermediate filaments appears typical of a mature astroglial cell lineage, since they fundamentally express GFAP immunoreactivity. A Western-blot analysis reveals a GFAP-positive single band, common to the different nervous areas. This immunohistochemical study shows that the star-shaped astrocytes have a different distribution in saurians and while the glial pattern of A. sagrei is more evolved than in urodeles it remains immature as compared with crocodilians, avians, and mammals. This condition suggests that reptiles represent a fundamental step in the phylogenetic evolution of the vertebrate glial cells. PMID:16086399

  9. Differential association of cardiorespiratory fitness and central adiposity among US adolescents and adults: A quantile regression approach.

    PubMed

    McDonald, Samantha M; Ortaglia, Andrew; Bottai, Matteo; Supino, Christina

    2016-07-01

    Previous studies assessing the association between cardiorespiratory fitness (CRF) and waist circumference (WC) have often restricted their evaluation to the association of CRF on average WC. Consequently, the assessment of important variations in the relationship of CRF across the WC distribution was precluded. The purpose of this study was to comprehensively evaluate the association between CRF and the distribution of WC using quantile regression. Secondary data analysis was conducted using data from the 1999-2004 NHANES. Participants (n=8260) aged 12-49years with complete data on estimated maximal oxygen consumption and WC were included. Quantile regression models were performed to assess the association between CRF and the 10th, 25th, 50th, 75th and 90th WC percentiles and were adjusted for age and race/ethnicity. For male and female adolescents with high CRF compared to low-fit counterparts, significant negative estimates (2.8 to 20.2cm and 2.3 to 11.2cm, respectively) were observed across most WC percentiles. Similarly, among male and female adults, high CRF was associated with significant reductions in WC across all percentiles (9.5 to 12.0cm and 3.7 to 9.2cm, respectively). For both populations, an increasing trend in the magnitude of the association of high CRF across the WC percentiles was observed. CRF appears to have a differential relationship across the WC distribution with the largest reductions in WC were found among high-fit individuals with the greatest amount of central adiposity (WC≥90th percentile). Additionally, this differential association highlights the significant limitations of statistical techniques used in previous analyses which focused on the center of the distribution. PMID:27002254

  10. The expression pattern of Adam10 in the central nervous system of adult mice: Detection by in situ hybridization combined with immunohistochemistry staining.

    PubMed

    Guo, Zhi-Bao; Su, Ying-Ying; Wang, Yi-Hui; Wang, Wei; Guo, Da-Zhi

    2016-09-01

    ADAM10 (a disintegrin and metalloprotease 10) is a member of the ADAMs family, which is key in the development of the nervous system, by regulating proliferation, migration, differentiation and survival of various cells, including axonal growth and myelination. Previous studies have investigated the embryonic or postnatal expression of ADAM10, however, detailed information regarding its cellular distribution in the adult stage, to the best of our knowledge, is not available. The present study investigated the expression pattern of the ADAM10 gene in the adult mouse central nervous system (CNS) using an ADAM10 complementary RNA probe for in situ hybridization (ISH). Immunohistochemical staining was used to identify the type of the ISH staining‑positive cells with neuron‑ or astrocyte‑specific antibodies. The results of the current study demonstrated that the ADAM10 gene was predominantly expressed in the neurons of the cerebral cortex, hippocampus, thalamus and cerebellar granular cells in adult mouse CNS. PMID:27431484

  11. The expression pattern of Adam10 in the central nervous system of adult mice: Detection by in situ hybridization combined with immunohistochemistry staining

    PubMed Central

    Guo, Zhi-Bao; Su, Ying-Ying; Wang, Yi-Hui; Wang, Wei; Guo, Da-Zhi

    2016-01-01

    ADAM10 (a disintegrin and metalloprotease 10) is a member of the ADAMs family, which is key in the development of the nervous system, by regulating proliferation, migration, differentiation and survival of various cells, including axonal growth and myelination. Previous studies have investigated the embryonic or postnatal expression of ADAM10, however, detailed information regarding its cellular distribution in the adult stage, to the best of our knowledge, is not available. The present study investigated the expression pattern of the ADAM10 gene in the adult mouse central nervous system (CNS) using an ADAM10 complementary RNA probe for in situ hybridization (ISH). Immunohistochemical staining was used to identify the type of the ISH staining-positive cells with neuron- or astrocyte-specific antibodies. The results of the current study demonstrated that the ADAM10 gene was predominantly expressed in the neurons of the cerebral cortex, hippocampus, thalamus and cerebellar granular cells in adult mouse CNS. PMID:27431484

  12. Moderate-Heavy Alcohol Consumption Lifestyle in Older Adults Is Associated with Altered Central Executive Network Community Structure during Cognitive Task.

    PubMed

    Mayhugh, Rhiannon E; Moussa, Malaak N; Simpson, Sean L; Lyday, Robert G; Burdette, Jonathan H; Porrino, Linda J; Laurienti, Paul J

    2016-01-01

    Older adults today consume more alcohol than previous generations, the majority being social drinkers. The effects of heavy alcohol use on brain functioning closely resemble age-related changes, but it is not known if moderate-heavy alcohol consumption intensifies brain aging. Whether a lifestyle of moderate-heavy alcohol use in older adults increased age-related brain changes was examined. Forty-one older adults (65-80 years) that consumed light (< 2 drinks/week and ≥ 1 drink/month, n = 20) or moderate-heavy (7-21 drinks/week, non-bingers, n = 21) amounts of alcohol were enrolled. Twenty-two young adults (24-35 years) were also enrolled (light, n = 11 and moderate-heavy, n = 11). Functional brain networks based on magnetic resonance imaging data were generated for resting state and during a working memory task. Whole-brain, Central Executive Network (CEN), and Default Mode Network (DMN) connectivity were assessed in light and moderate-heavy alcohol consuming older adults with comparisons to young adults. The older adults had significantly lower whole brain connectivity (global efficiency) and lower regional connectivity (community structure) in the CEN during task and in the DMN at rest. Moderate-heavy older drinkers did not exhibit whole brain connectivity differences compared to the low drinkers. However, decreased CEN connectivity was observed during the task. There were no differences in the DMN connectivity between drinking groups. Taken together, a lifestyle including moderate-heavy alcohol consumption may be associated with further decreases in brain network connectivity within task-related networks in older adults. Further research is required to determine if this decrease is compensatory or an early sign of decline. PMID:27494180

  13. Moderate-Heavy Alcohol Consumption Lifestyle in Older Adults Is Associated with Altered Central Executive Network Community Structure during Cognitive Task

    PubMed Central

    Moussa, Malaak N.; Simpson, Sean L.; Lyday, Robert G.; Burdette, Jonathan H.; Porrino, Linda J.; Laurienti, Paul J.

    2016-01-01

    Older adults today consume more alcohol than previous generations, the majority being social drinkers. The effects of heavy alcohol use on brain functioning closely resemble age-related changes, but it is not known if moderate-heavy alcohol consumption intensifies brain aging. Whether a lifestyle of moderate-heavy alcohol use in older adults increased age-related brain changes was examined. Forty-one older adults (65–80 years) that consumed light (< 2 drinks/week and ≥ 1 drink/month, n = 20) or moderate-heavy (7–21 drinks/week, non-bingers, n = 21) amounts of alcohol were enrolled. Twenty-two young adults (24–35 years) were also enrolled (light, n = 11 and moderate-heavy, n = 11). Functional brain networks based on magnetic resonance imaging data were generated for resting state and during a working memory task. Whole-brain, Central Executive Network (CEN), and Default Mode Network (DMN) connectivity were assessed in light and moderate-heavy alcohol consuming older adults with comparisons to young adults. The older adults had significantly lower whole brain connectivity (global efficiency) and lower regional connectivity (community structure) in the CEN during task and in the DMN at rest. Moderate-heavy older drinkers did not exhibit whole brain connectivity differences compared to the low drinkers. However, decreased CEN connectivity was observed during the task. There were no differences in the DMN connectivity between drinking groups. Taken together, a lifestyle including moderate-heavy alcohol consumption may be associated with further decreases in brain network connectivity within task-related networks in older adults. Further research is required to determine if this decrease is compensatory or an early sign of decline. PMID:27494180

  14. Mammalian development in space

    NASA Technical Reports Server (NTRS)

    Ronca, April E.

    2003-01-01

    Life on Earth, and thus the reproductive and ontogenetic processes of all extant species and their ancestors, evolved under the constant influence of the Earth's l g gravitational field. These considerations raise important questions about the ability of mammals to reproduce and develop in space. In this chapter, I review the current state of our knowledge of spaceflight effects on developing mammals. Recent studies are revealing the first insights into how the space environment affects critical phases of mammalian reproduction and development, viz., those events surrounding fertilization, embryogenesis, pregnancy, birth, postnatal maturation and parental care. This review emphasizes fetal and early postnatal life, the developmental epochs for which the greatest amounts of mammalian spaceflight data have been amassed. The maternal-offspring system, the coordinated aggregate of mother and young comprising mammalian development, is of primary importance during these early, formative developmental phases. The existing research supports the view that biologically meaningful interactions between mothers and offspring are changed in the weightlessness of space. These changes may, in turn, cloud interpretations of spaceflight effects on developing offspring. Whereas studies of mid-pregnant rats in space have been extraordinarily successful, studies of young rat litters launched at 9 days of postnatal age or earlier, have been encumbered with problems related to the design of in-flight caging and compromised maternal-offspring interactions. Possibilities for mammalian birth in space, an event that has not yet transpired, are considered. In the aggregate, the results indicate a strong need for new studies of mammalian reproduction and development in space. Habitat development and systematic ground-based testing are important prerequisites to future research with young postnatal rodents in space. Together, the findings support the view that the environment within which young

  15. Perceptions of Young Adult Central Nervous System Cancer Survivors and Their Parents Regarding Career Development and Employment

    ERIC Educational Resources Information Center

    Strauser, David R.; Wagner, Stacia; Chan, Fong; Wong, Alex W. K.

    2014-01-01

    Purpose: Identify barriers to career development and employment from both the survivor and parent perspective. Method: Young adult survivors (N = 43) and their parents participated in focus groups to elicit information regarding perceptions regarding career development and employment. Results: Perceptions of both the young adults and parents…

  16. Captures of western corn rootworm (Coleoptera: Chrysomelidae) adults with Pherocon AM and vial traps in four crops in east central Illinois.

    PubMed

    Rondon, Silvia I; Gray, Michael E

    2003-06-01

    It is hypothesized that the long-term rotation of maize (Zea mays L.) and soybean (Glycine max L.) in east central Illinois has caused a significant change in the ovipositional behavior of the western corn rootworm, Diabrotica virgifera virgifera LeConte. Since the mid 1990s in east central Illinois, western corn rootworm adults have been observed feeding on soybean foliage and also now use soybean fields as egg laying sites. This behavioral adaptation has greatly decreased the effectiveness of rotation as a pest management tactic. By using Pherocon AM and vial traps, we evaluated the influence of maize, soybean, oat stubble (Avena sativa L.), and alfalfa (Medicago sativa L.) on male and female adult western corn rootworm densities from April 1998 through September 2000 near Urbana, IL. Our results indicated that western corn rootworm adults are common inhabitants of maize, soybean, oat stubble, and alfalfa. Trapping efforts with both Pherocon AM (attractive) and vial traps (passive) revealed that initial densities of both male and female western corn rootworm adults were greater in maize. Soon after emergence, densities of females began to decline within maize and increase in other crops (soybean, oat stubble, and alfalfa). Results from this experiment support the hypothesis that variant western corn rootworm females in east central Illinois are colonizing crops other than maize at densities of potential economic importance. Those producers who choose to rotate maize with soybean or alfalfa may remain at risk to economic larval injury to maize roots. Potentially, oat stubble also may support levels of western corn rootworm females resulting in sufficient oviposition to cause economic losses to rotated maize the following season. PMID:12852611

  17. Mammalian Septins Nomenclature

    PubMed Central

    Macara, Ian G.; Baldarelli, Richard; Field, Christine M.; Glotzer, Michael; Hayashi, Yasuhide; Hsu, Shu-Chan; Kennedy, Mary B.; Kinoshita, Makoto; Longtine, Mark; Low, Claudia; Maltais, Lois J.; McKenzie, Louise; Mitchison, Timothy J.; Nishikawa, Toru; Noda, Makoto; Petty, Elizabeth M.; Peifer, Mark; Pringle, John R.; Robinson, Phillip J.; Roth, Dagmar; Russell, S.E. Hilary; Stuhlmann, Heidi; Tanaka, Manami; Tanaka, Tomoo; Trimble, William S.; Ware, Jerry; Zeleznik-Le, Nancy J.; Zieger, Barbara

    2002-01-01

    There are 10 known mammalian septin genes, some of which produce multiple splice variants. The current nomenclature for the genes and gene products is very confusing, with several different names having been given to the same gene product and distinct names given to splice variants of the same gene. Moreover, some names are based on those of yeast or Drosophila septins that are not the closest homologues. Therefore, we suggest that the mammalian septin field adopt a common nomenclature system, based on that adopted by the Mouse Genomic Nomenclature Committee and accepted by the Human Genome Organization Gene Nomenclature Committee. The human and mouse septin genes will be named SEPT1–SEPT10 and Sept1–Sept10, respectively. Splice variants will be designated by an underscore followed by a lowercase “v” and a number, e.g., SEPT4_v1. PMID:12475938

  18. Mammalian sweet taste receptors.

    PubMed

    Nelson, G; Hoon, M A; Chandrashekar, J; Zhang, Y; Ryba, N J; Zuker, C S

    2001-08-10

    The sense of taste provides animals with valuable information about the quality and nutritional value of food. Previously, we identified a large family of mammalian taste receptors involved in bitter taste perception (the T2Rs). We now report the characterization of mammalian sweet taste receptors. First, transgenic rescue experiments prove that the Sac locus encodes T1R3, a member of the T1R family of candidate taste receptors. Second, using a heterologous expression system, we demonstrate that T1R2 and T1R3 combine to function as a sweet receptor, recognizing sweet-tasting molecules as diverse as sucrose, saccharin, dulcin, and acesulfame-K. Finally, we present a detailed analysis of the patterns of expression of T1Rs and T2Rs, thus providing a view of the representation of sweet and bitter taste at the periphery. PMID:11509186

  19. Rheotaxis guides mammalian sperm

    PubMed Central

    Miki, Kiyoshi; Clapham, David E

    2013-01-01

    Background In sea urchins, spermatozoan motility is altered by chemotactic peptides, giving rise to the assumption that mammalian eggs also emit chemotactic agents that guide spermatozoa through the female reproductive tract to the mature oocyte. Mammalian spermatozoa indeed undergo complex adaptations within the female (the process of capacitation) that are initiated by agents ranging from pH to progesterone, but these factors are not necessarily taxic. Currently, chemotaxis, thermotaxis, and rheotaxis have not been definitively established in mammals. Results Here, we show that positive rheotaxis, the ability of organisms to orient and swim against the flow of surrounding fluid, is a major taxic factor for mouse and human sperm. This flow is generated within 4 hours of sexual stimulation and coitus in female mice; prolactin-triggered oviductal fluid secretion clears the oviduct of debris, lowers viscosity, and generates the stream that guides sperm migration in the oviduct. Rheotaxic movement is demonstrated in capacitated and uncapacitated spermatozoa in low and high viscosity medium. Finally, we show that a unique sperm motion we quantify using the sperm head's rolling rate reflects sperm rotation that generates essential force for positioning the sperm in the stream. Rotation requires CatSper channels, presumably by enabling Ca2+ influx. Conclusions We propose that rheotaxis is a major determinant of sperm guidance over long distances in the mammalian female reproductive tract. Coitus induces fluid flow to guide sperm in the oviduct. Sperm rheotaxis requires rotational motion during CatSper channel-dependent hyperactivated motility. PMID:23453951

  20. PI3K-GSK3 signalling regulates mammalian axon regeneration by inducing the expression of Smad1

    NASA Astrophysics Data System (ADS)

    Saijilafu; Hur, Eun-Mi; Liu, Chang-Mei; Jiao, Zhongxian; Xu, Wen-Lin; Zhou, Feng-Quan

    2013-10-01

    In contrast to neurons in the central nervous system, mature neurons in the mammalian peripheral nervous system (PNS) can regenerate axons after injury, in part, by enhancing intrinsic growth competence. However, the signalling pathways that enhance the growth potential and induce spontaneous axon regeneration remain poorly understood. Here we reveal that phosphatidylinositol 3-kinase (PI3K) signalling is activated in response to peripheral axotomy and that PI3K pathway is required for sensory axon regeneration. Moreover, we show that glycogen synthase kinase 3 (GSK3), rather than mammalian target of rapamycin, mediates PI3K-dependent augmentation of the growth potential in the PNS. Furthermore, we show that PI3K-GSK3 signal is conveyed by the induction of a transcription factor Smad1 and that acute depletion of Smad1 in adult mice prevents axon regeneration in vivo. Together, these results suggest PI3K-GSK3-Smad1 signalling as a central module for promoting sensory axon regeneration in the mammalian nervous system.

  1. Ectopic expression of polysialylated neural cell adhesion molecule in adult macaque Schwann cells promotes their migration and remyelination potential in the central nervous system

    PubMed Central

    Bachelin, C.; Zujovic, V.; Buchet, D.; Mallet, J.

    2010-01-01

    Recent findings suggested that inducing neural cell adhesion molecule polysialylation in rodents is a promising strategy for promoting tissue repair in the injured central nervous system. Since autologous grafting of Schwann cells is one potential strategy to promote central nervous system remyelination, it is essential to show that such a strategy can be translated to adult primate Schwann cells and is of interest for myelin diseases. Adult macaque Schwann cells were transduced with a lentiviral vector encoding sialyltransferase, an enzyme responsible for neural cell adhesion molecule polysialylation. In vitro, we found that ectopic expression of polysialylate promoted adult macaque Schwann cell migration and improved their integration among astrocytes in vitro without modifying their antigenic properties as either non-myelinating or pro-myelinating. In addition, forced expression of polysialylate in adult macaque Schwann cells decreased their adhesion with sister cells. To investigate the ability of adult macaque Schwann cells to integrate and migrate in vivo, focally induced demyelination was targeted to the spinal cord dorsal funiculus of nude mice, and both control and sialyltransferase expressing Schwann cells overexpressing green fluorescein protein were grafted remotely from the lesion site. Analysis of the spatio-temporal distribution of the grafted Schwann cells performed in toto and in situ, showed that in both groups, Schwann cells migrated towards the lesion site. However, migration of sialyltransferase expressing Schwann cells was more efficient than that of control Schwann cells, leading to their accelerated recruitment by the lesion. Moreover, ectopic expression of polysialylated neural cell adhesion molecule promoted adult macaque Schwann cell interaction with reactive astrocytes when exiting the graft, and their ‘chain-like’ migration along the dorsal midline. The accelerated migration of sialyltransferase expressing Schwann cells to the

  2. Landscape analysis of adult codling moth (Lepidoptera: Tortricidae) distribution and dispersal within typical agroecosystems dominated by apple production in central Chile.

    PubMed

    Basoalto, E; Miranda, M; Knight, A L; Fuentes-Contreras, E

    2010-10-01

    We analyzed the spatial distribution and dispersal of codling moth, Cydia pomonella (L.), adults within two heterogeneous agroecosystems typical of central Chile: commercial apple, Malus domestica Borkhausen, orchards surrounded by various unmanaged host plants. Both a geostatistical analysis of catches of adult males with a grid of sex pheromone-baited traps and an immunological self-marking technique combined with traps baited with a male and female attractant were used. The spatial analyses identified the key sources of moths within these diverse landscapes. Codling moth catches in traps were spatially associated within distances of ≈ 150-300 m. Similarly, the mean distance from the immunological self-marking plots within the commercial apple orchard to the traps that captured marked adults was 282 m. In contrast, the mean distance in the capture of marked moths from unmanaged self-marking plots to a commercial orchard was 828 m. These data suggest that the success of any future area-wide management programs for codling moth in Chilean pome fruit must include a component for managing or removing noncommercial hosts that surround orchards. This analysis also suggests that the selection pressure for resistance imposed by insecticide sprays within managed orchards is likely dampened by the influx of susceptible moths from unmanaged sites common in central Chile. PMID:22546434

  3. Emergency Department Visits Involving Nonmedical Use of Central Nervous System Stimulants among Adults Aged 18 to 34 ...

    MedlinePlus

    ... Emergency Department (ED) Visits Involving Nonmedical Use of Pharmaceuticals* among Adults Aged 18 to 34, by Alcohol ... 2007 2008 2009 2010 2011 * Nonmedical use of pharmaceuticals includes taking more than the prescribed dose of ...

  4. Appraisals of discriminatory events among adult offspring of Indian residential school survivors: the influences of identity centrality and past perceptions of discrimination.

    PubMed

    Bombay, Amy; Matheson, Kimberly; Anisman, Hymie

    2014-01-01

    As part of a government policy of assimilation beginning in the mid-1800s, a large proportion of Aboriginal children in Canada were forcibly removed from their homes to attend Indian Residential Schools (IRSs), a practice which continued into the 1990s. This traumatic experience had lasting negative effects not only on those who attended but also on their offspring, who were previously found to report higher levels of perceived discrimination and depressive symptoms compared with Aboriginal adults whose families were not directly affected by IRSs. In attempt to elucidate the processes involved in these previous findings, the current study (N = 399) revealed that greater levels of past perceptions of discrimination among IRS offspring, together with their greater likelihood of considering their Aboriginal heritage to be a central component of their self-concept (i.e., high identity centrality), were associated with an increased likelihood of appraising subsequent negative intergroup scenarios to be a result of discrimination and as threatening to their well-being. In turn, these altered appraisals of threat in response to the scenarios were associated with higher levels of depressive symptoms relative to non-IRS adults. The apparent reinforcing relationships between past discrimination, identity centrality, and appraisals of discrimination and threat in intergroup interactions highlight the need for interventions targeting this cycle that appears to contribute to heightened psychological distress among offspring of those who were directly victimized by collective race-based traumas. PMID:23834257

  5. How to Build Transcriptional Network Models of Mammalian Pattern Formation

    PubMed Central

    Kioussi, Chrissa; Gross, Michael K.

    2008-01-01

    Background Genetic regulatory networks of sequence specific transcription factors underlie pattern formation in multicellular organisms. Deciphering and representing the mammalian networks is a central problem in development, neurobiology, and regenerative medicine. Transcriptional networks specify intermingled embryonic cell populations during pattern formation in the vertebrate neural tube. Each embryonic population gives rise to a distinct type of adult neuron. The homeodomain transcription factor Lbx1 is expressed in five such populations and loss of Lbx1 leads to distinct respecifications in each of the five populations. Methodology/Principal Findings We have purified normal and respecified pools of these five populations from embryos bearing one or two copies of the null Lbx1GFP allele, respectively. Microarrays were used to show that expression levels of 8% of all transcription factor genes were altered in the respecified pool. These transcription factor genes constitute 20–30% of the active nodes of the transcriptional network that governs neural tube patterning. Half of the 141 regulated nodes were located in the top 150 clusters of ultraconserved non-coding regions. Generally, Lbx1 repressed genes that have expression patterns outside of the Lbx1-expressing domain and activated genes that have expression patterns inside the Lbx1-expressing domain. Conclusions/Significance Constraining epistasis analysis of Lbx1 to only those cells that normally express Lbx1 allowed unprecedented sensitivity in identifying Lbx1 network interactions and allowed the interactions to be assigned to a specific set of cell populations. We call this method ANCEA, or active node constrained epistasis analysis, and think that it will be generally useful in discovering and assigning network interactions to specific populations. We discuss how ANCEA, coupled with population partitioning analysis, can greatly facilitate the systematic dissection of transcriptional networks that

  6. Older Adults Accessing HIV Care and Treatment and Adherence in the IeDEA Central Africa Cohort

    PubMed Central

    Newman, Jamie; Iriondo-Perez, Jeniffer; Hemingway-Foday, Jennifer; Freeman, Anna; Akam, Wilfred; Balimba, Ashu; Kalenga, Lucien; Mbaya, Marcel; Mfangam Molu, Brigitte; Mukumbi, Henri; Niyongabo, Théodore; Atibu, Joseph; Azinyue, Innocent; Kiumbu, Modeste

    2012-01-01

    Background. Very little is known about older adults accessing HIV care in sub-Saharan Africa. Materials and Methods. Data were obtained from 18,839 HIV-positive adults at 10 treatment programs in Burundi, Cameroon, and the Democratic Republic of Congo. We compared characteristics of those aged 50+ with those aged 18–49 using chi-square tests. Logistic regression was used to determine if age was associated with medication adherence. Results. 15% of adults were 50+ years. Those aged 50+ were more evenly distributed between women and men (56% versus 44%) as compared to those aged 18–49 (71% versus 29%) and were more likely to be hypertensive (8% versus 3%) (P < 0.05). Those aged 50+ were more likely to be adherent to their medications than those aged 18–49 (P < 0.001). Adults who were not heavy drinkers reported better adherence as compared to those who reported drinking three or more alcoholic beverages per day (P < 0.001). Conclusions. Older adults differed from their younger counterparts in terms of medication adherence, sociodemographic, behavioral, and clinical characteristics. PMID:22400105

  7. Fate Mapping Mammalian Corneal Epithelia.

    PubMed

    Richardson, Alexander; Wakefield, Denis; Di Girolamo, Nick

    2016-04-01

    The anterior aspect of the cornea consists of a stratified squamous epithelium, thought to be maintained by a rare population of stem cells (SCs) that reside in the limbal transition zone. Although migration of cells that replenish the corneal epithelium has been studied for over a century, the process is still poorly understood and not well characterized. Numerous techniques have been employed to examine corneal epithelial dynamics, including visualization by light microscopy, the incorporation of vital dyes and DNA labels, and transplantation of genetically marked cells that have acted as cell and lineage beacons. Modern-day lineage tracing utilizes molecular methods to determine the fate of a specific cell and its progeny over time. Classically employed in developmental biology, lineage tracing has been used more recently to track the progeny of adult SCs in a number of organs to pin-point their location and understand their movement and influence on tissue regeneration. This review highlights key discoveries that have led researchers to develop cutting-edge genetic tools to effectively and more accurately monitor turnover and displacement of cells within the mammalian corneal epithelium. Collating information on the basic biology of SCs will have clinical ramifications in furthering our knowledge of the processes that govern their role in homeostasis, wound-healing, transplantation, and how we can improve current unsatisfactory SC-based therapies for patients suffering blinding corneal disease. PMID:26774909

  8. Mammalian Endogenous Retroviruses.

    PubMed

    Mager, Dixie L; Stoye, Jonathan P

    2015-02-01

    Over 40% of mammalian genomes comprise the products of reverse transcription. Among such retrotransposed sequences are those characterized by the presence of long terminal repeats (LTRs), including the endogenous retroviruses (ERVs), which are inherited genetic elements closely resembling the proviruses formed following exogenous retrovirus infection. Sequences derived from ERVs make up at least 8 to 10% of the human and mouse genomes and range from ancient sequences that predate mammalian divergence to elements that are currently still active. In this chapter we describe the discovery, classification and origins of ERVs in mammals and consider cellular mechanisms that have evolved to control their expression. We also discuss the negative effects of ERVs as agents of genetic disease and cancer and review examples of ERV protein domestication to serve host functions, as in placental development. Finally, we address growing evidence that the gene regulatory potential of ERV LTRs has been exploited multiple times during evolution to regulate genes and gene networks. Thus, although recently endogenized retroviral elements are often pathogenic, those that survive the forces of negative selection become neutral components of the host genome or can be harnessed to serve beneficial roles. PMID:26104559

  9. Adult mouse brain gene expression patterns bear an embryologic imprint

    PubMed Central

    Zapala, Matthew A.; Hovatta, Iiris; Ellison, Julie A.; Wodicka, Lisa; Del Rio, Jo A.; Tennant, Richard; Tynan, Wendy; Broide, Ron S.; Helton, Rob; Stoveken, Barbara S.; Winrow, Christopher; Lockhart, Daniel J.; Reilly, John F.; Young, Warren G.; Bloom, Floyd E.; Lockhart, David J.; Barlow, Carrolee

    2005-01-01

    The current model to explain the organization of the mammalian nervous system is based on studies of anatomy, embryology, and evolution. To further investigate the molecular organization of the adult mammalian brain, we have built a gene expression-based brain map. We measured gene expression patterns for 24 neural tissues covering the mouse central nervous system and found, surprisingly, that the adult brain bears a transcriptional “imprint” consistent with both embryological origins and classic evolutionary relationships. Embryonic cellular position along the anterior–posterior axis of the neural tube was shown to be closely associated with, and possibly a determinant of, the gene expression patterns in adult structures. We also observed a significant number of embryonic patterning and homeobox genes with region-specific expression in the adult nervous system. The relationships between global expression patterns for different anatomical regions and the nature of the observed region-specific genes suggest that the adult brain retains a degree of overall gene expression established during embryogenesis that is important for regional specificity and the functional relationships between regions in the adult. The complete collection of extensively annotated gene expression data along with data mining and visualization tools have been made available on a publicly accessible web site (www.barlow-lockhart-brainmapnimhgrant.org). PMID:16002470

  10. Development and validation of two food portion photograph books to assess dietary intake among adults and children in Central Africa.

    PubMed

    Amougou, Norbert; Cohen, Emmanuel; Mbala, Marie L; Grosdidier, Basile; Bernard, Jonathan Y; Saïd-Mohamed, Rihlat; Pasquet, Patrick

    2016-03-01

    Owing to nutritional transition in Cameroon, one in two adults is overweight and one in five is obese, and 8·1 % of children are overweight and 2·1 % are obese. Given this phenomenon, dietary intake assessment is needed to establish appropriate preventive nutrition-sensitive strategies. Our aim was to develop and test the validity of two food portion photograph books (FPPB) to be used as visual aids for adults and children taking part in a 24-h dietary recall. To design FPPB, interviews and focus group discussions were undertaken with women to obtain consensus on the local categorisation of foods. For each cooked and weighed food, three photographs of the average small, medium and large serving portion sizes were taken, and four intermediary portion sizes were calculated. To validate the FPPB, a sample of adults (361) and children (224) were asked, at meal times, to self-serve a food portion prepared in the household and the portion sizes were weighed; 24 h after the measurement, the same subjects were shown the appropriate FPPB and were asked to indicate the food and the portion they consumed. In adults, of the 821 portions tested, 77 % were accurately estimated, whereas in children 74 % of the 556 portions tested were accurately estimated. For both groups, the small- and medium-sized portions were frequently selected and accurately estimated (>70 %). Our findings suggest that the adult and children's FPPB can be used in Cameroon to estimate food portion sizes, and thus nutritional intake in the frame of the 24-h dietary recall. PMID:26786057

  11. Reduction of Central Line-Associated Bloodstream Infection Rates in Patients in the Adult Intensive Care Unit.

    PubMed

    Wallace, Mary C; Macy, Deborah L

    2016-01-01

    Central line-associated bloodstream infections (CLABSIs) prolong hospital stays and increase cost, morbidity, and mortality. An intensive care unit (ICU) in a suburban Baltimore hospital reduced CLABSI rates to zero in 2012, by revising central venous access device policies and initiatives, which included a bloodstream infection alert system, bundle compliance monitoring and routine evaluation, and use of positive displacement needleless connectors. The hospital's ICU infection rate decreased from 2.9/1000 central-line days in 2010 to 0.8 by 2011, 0 by 2012, and 0.91 in 2013. The utilization ratio was 0.64 in 2011, 0.60 in 2012, and 0.58 in 2013. CLABSI prevention involves all disciplines and requires staff accountability for patient safety. PMID:26714119

  12. Higher sika deer density is associated with higher local abundance of Haemaphysalis longicornis nymphs and adults but not larvae in central Japan.

    PubMed

    Tsukada, Hideharu; Nakamura, Yoshio; Kamio, Tsugihiko; Inokuma, Hisashi; Hanafusa, Yasuko; Matsuda, Naoko; Maruyama, Tetsuya; Ohba, Takahiro; Nagata, Koji

    2014-02-01

    Haemaphysalis longicornis (Acari: Ixodidae) is one of the most common and important arthropod disease vectors in Japan, carrying Japanese spotted fever and bovine theileriosis. The recent expansion of sika deer (Cervus nippon, Artiodactyla: Cervidae) populations, the most common wild host of H. longicornis, has also caused concern about increasing the risk of vector-borne diseases in Japan. We used generalized linear mixed model analysis to determine the relative contribution of deer density and other biological and abiotic factors on the abundance of H. longicornis ticks questing at each developmental stage. A total of 6223 H. longicornis adults, nymphs, and larvae were collected from 70 sites in three regions of central Japan. The abundance of questing adult and nymphal ticks was associated with deer density and other biotic and abiotic factors. However, the abundance of questing larvae showed no association with deer density but did show an association with other biotic and abiotic factors. These findings show that a high density of deer along with other biotic and abiotic factors is associated with increased risk of vector-borne diseases through amplified local abundance of questing nymphal and adult H. longicornis. Further, questing larvae abundance is likely regulated by environmental conditions and is likely correlated with survival potential or the distribution of other host species. PMID:23702338

  13. Global Epigenomic Reconfiguration During Mammalian Brain Development

    PubMed Central

    Nery, Joseph R.; Urich, Mark; Puddifoot, Clare A.; Johnson, Nicholas D.; Lucero, Jacinta; Huang, Yun; Dwork, Andrew J.; Schultz, Matthew D.; Yu, Miao; Tonti-Filippini, Julian; Heyn, Holger; Hu, Shijun; Wu, Joseph C.; Rao, Anjana; Esteller, Manel; He, Chuan; Haghighi, Fatemeh G.; Sejnowski, Terrence J.; Behrens, M. Margarita; Ecker, Joseph R.

    2013-01-01

    DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Last, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain and that CG demethylation at these hmC-poised loci depends on Tet2 activity. PMID:23828890

  14. Participation in a Technological World: The Meaning of Educational Technology in the Lives of Young Adult Central American Immigrants.

    ERIC Educational Resources Information Center

    Pruitt-Mentle, Davina S.

    Many communities throughout the United States are experiencing a large influx of Central American immigrants. Langley Park, Maryland is typical of the pockets that are formed by the new arrivals. Community members of Latino background now account for 60% of the population, while in 1990 they were only 40% (US Census, 2000). As the immigrants move…

  15. Mammalian Kidney Development: Principles, Progress, and Projections

    PubMed Central

    Little, Melissa H.; McMahon, Andrew P.

    2012-01-01

    The mammalian kidney is a vital organ with considerable cellular complexity and functional diversity. Kidney development is notable for requiring distinct but coincident tubulogenic processes involving reciprocal inductive signals between mesenchymal and epithelial progenitor compartments. Key molecular pathways mediating these interactions have been identified. Further, advances in the analysis of gene expression and gene activity, coupled with a detailed knowledge of cell origins, are enhancing our understanding of kidney morphogenesis and unraveling the normal processes of postnatal repair and identifying disease-causing mechanisms. This article focuses on recent insights into central regulatory processes governing organ assembly and renal disease, and predicts future directions for the field. PMID:22550230

  16. The mammalian blastocyst.

    PubMed

    Frankenberg, Stephen R; de Barros, Flavia R O; Rossant, Janet; Renfree, Marilyn B

    2016-01-01

    The blastocyst is a mammalian invention that carries the embryo from cleavage to gastrulation. For such a simple structure, it exhibits remarkable diversity in its mode of formation, morphology, longevity, and intimacy with the uterine endometrium. This review explores this diversity in the light of the evolution of viviparity, comparing the three main groups of mammals: monotremes, marsupials, and eutherians. The principal drivers in blastocyst evolution were loss of yolk coupled with evolution of the placenta. An important outcome of blastocyst development is differentiation of two extraembryonic lineages (trophoblast and hypoblast) that contribute to the placenta. While in many species trophoblast segregation is often coupled with blastocyst formation, in marsupials and at least some Afrotherians, these events do not coincide. Thus, many questions regarding the conservation of molecular mechanisms controlling these events are of great interest but currently unresolved. For further resources related to this article, please visit the WIREs website. PMID:26799266

  17. Relationship between Seed Bank Expression, Adult Longevity and Aridity in Species of Chaetanthera (Asteraceae) in Central Chile

    PubMed Central

    ARROYO, M. T. K.; CHACON, P.; CAVIERES, L. A.

    2006-01-01

    • Background and Aims Broad surveys have detected inverse relationships between seed and adult longevity and between seed size and adult longevity. However, low and unpredictable precipitation is also associated with seed bank (SB) expression in semi-arid and arid areas. The relationship between adult longevity, SB formation, seed mass and aridity is examined in annual and perennial herbs of Chaetanthera (Asteraceae) from the Chilean Mediterranean-type climate and winter-rainfall desert areas over a precipitation range of one order of magnitude. • Methods Seeds of 18 species and subtaxa (32 populations) were buried in field locations, and exhumed after two successive germination periods. Seeds not germinating in the field were tested in a growth chamber, and remnant intact seed tested for viability. Seed banks were classed as transient or persistent. The effect of life form, species, population and burial time on persistent SB size was assessed with factorial ANOVA. Persistent seed bank size was compared with the Martonne aridity index (shown to be a surrogate for inter-annual variation in precipitation) and seed size using linear regression. ANCOVA assessed the effect of life-form on SB size with aridity as covariate. • Key Results Three species had a transient SB and 15 a persistent SB. ANOVA revealed a significant effect of life-form on SB size with annuals having larger SB size and greater capacity to form a persistent SB than perennials. Significant inter-population variation in SB size was found in 64 % of cases. Seed mass was negatively correlated with persistent SB size. Persistent seed bank size was significantly correlated with the Martonne aridity index in the perennial and annual species, with species from more arid areas having larger persistent SBs. However, when aridity was considered as a covariate, ANCOVA revealed no significant differences between the annual and perennial herbs. • Conclusions Persistent seed bank size in Chaetanthera

  18. The Treatment of Central Sleep Apnea Syndromes in Adults: Practice Parameters with an Evidence-Based Literature Review and Meta-Analyses

    PubMed Central

    Aurora, R. Nisha; Chowdhuri, Susmita; Ramar, Kannan; Bista, Sabin R.; Casey, Kenneth R.; Lamm, Carin I.; Kristo, David A.; Mallea, Jorge M.; Rowley, James A.; Zak, Rochelle S.; Tracy, Sharon L.

    2012-01-01

    The International Classification of Sleep Disorders, Second Edition (ICSD-2) distinguishes 5 subtypes of central sleep apnea syndromes (CSAS) in adults. Review of the literature suggests that there are two basic mechanisms that trigger central respiratory events: (1) post-hyperventilation central apnea, which may be triggered by a variety of clinical conditions, and (2) central apnea secondary to hypoventilation, which has been described with opioid use. The preponderance of evidence on the treatment of CSAS supports the use of continuous positive airway pressure (CPAP). Much of the evidence comes from investigations on CSAS related to congestive heart failure (CHF), but other subtypes of CSAS appear to respond to CPAP as well. Limited evidence is available to support alternative therapies in CSAS subtypes. The recommendations for treatment of CSAS are summarized as follows: CPAP therapy targeted to normalize the apnea-hypopnea index (AHI) is indicated for the initial treatment of CSAS related to CHF. (STANDARD)Nocturnal oxygen therapy is indicated for the treatment of CSAS related to CHF. (STANDARD)Adaptive Servo-Ventilation (ASV) targeted to normalize the apnea-hypopnea index (AHI) is indicated for the treatment of CSAS related to CHF. (STANDARD)BPAP therapy in a spontaneous timed (ST) mode targeted to normalize the apnea-hypopnea index (AHI) may be considered for the treatment of CSAS related to CHF only if there is no response to adequate trials of CPAP, ASV, and oxygen therapies. (OPTION)The following therapies have limited supporting evidence but may be considered for the treatment of CSAS related to CHF after optimization of standard medical therapy, if PAP therapy is not tolerated, and if accompanied by close clinical follow-up: acetazolamide and theophylline. (OPTION)Positive airway pressure therapy may be considered for the treatment of primary CSAS. (OPTION)Acetazolamide has limited supporting evidence but may be considered for the treatment of primary

  19. Central sleep apnea

    MedlinePlus

    ... pressure (CPAP) , bilevel positive airway pressure (BiPAP) or adaptive servo-ventilation (ASV). Some types of central sleep ... et al. The treatment of central sleep apnea syndromes in adults: practice parameters with an evidence-based ...

  20. Factors Influencing the Central Nervous System Distribution of a Novel Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitor GSK2126458: Implications for Overcoming Resistance with Combination Therapy for Melanoma Brain Metastases.

    PubMed

    Vaidhyanathan, Shruthi; Wilken-Resman, Brynna; Ma, Daniel J; Parrish, Karen E; Mittapalli, Rajendar K; Carlson, Brett L; Sarkaria, Jann N; Elmquist, William F

    2016-02-01

    Small molecule inhibitors targeting the mitogen-activated protein kinase pathway (Braf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase) have had success in extending survival for patients with metastatic melanoma. Unfortunately, resistance may occur via cross-activation of alternate signaling pathways. One approach to overcome resistance is to simultaneously target the phosphoinositide 3-kinase/mammalian target of rapamycin signaling pathway. Recent reports have shown that GSK2126458 [2,4-difluoro-N-(2-methoxy-5-(4-(pyridazin-4-yl)quinolin-6-yl)pyridin-3-yl) benzenesulfonamide], a dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor, can overcome acquired resistance to Braf and mitogen-activated protein kinase kinase inhibitors in vitro. These resistance mechanisms may be especially important in melanoma brain metastases because of limited drug delivery across the blood-brain barrier. The purpose of this study was to investigate factors that influence the brain distribution of GSK2126458 and to examine the efficacy of GSK2126458 in a novel patient-derived melanoma xenograft (PDX) model. Both in vitro and in vivo studies indicate that GSK2126458 is a substrate for P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp), two dominant active efflux transporters in the blood-brain barrier. The steady-state brain distribution of GSK2126458 was 8-fold higher in the P-gp/Bcrp knockout mice compared with the wild type. We also observed that when simultaneously infused to steady state, GSK212658, dabrafenib, and trametinib, a rational combination to overcome mitogen-activated protein kinase inhibitor resistance, all had limited brain distribution. Coadministration of elacridar, a P-gp/Bcrp inhibitor, increased the brain distribution of GSK2126458 by approximately 7-fold in wild-type mice. In the PDX model, GSK2126458 showed efficacy in flank tumors but was ineffective in intracranial melanoma. These results show that

  1. The role of cannabinoids in adult neurogenesis

    PubMed Central

    Prenderville, Jack A; Kelly, Áine M; Downer, Eric J

    2015-01-01

    The processes underpinning post-developmental neurogenesis in the mammalian brain continue to be defined. Such processes involve the proliferation of neural stem cells and neural progenitor cells (NPCs), neuronal migration, differentiation and integration into a network of functional synapses within the brain. Both intrinsic (cell signalling cascades) and extrinsic (neurotrophins, neurotransmitters, cytokines, hormones) signalling molecules are intimately associated with adult neurogenesis and largely dictate the proliferative activity and differentiation capacity of neural cells. Cannabinoids are a unique class of chemical compounds incorporating plant-derived cannabinoids (the active components of Cannabis sativa), the endogenous cannabinoids and synthetic cannabinoid ligands, and these compounds are becoming increasingly recognized for their roles in neural developmental processes. Indeed, cannabinoids have clear modulatory roles in adult neurogenesis, probably through activation of both CB1 and CB2 receptors. In recent years, a large body of literature has deciphered the signalling networks involved in cannabinoid-mediated regulation of neurogenesis. This timely review summarizes the evidence that the cannabinoid system is intricately associated with neuronal differentiation and maturation of NPCs and highlights intrinsic/extrinsic signalling mechanisms that are cannabinoid targets. Overall, these findings identify the central role of the cannabinoid system in adult neurogenesis in the hippocampus and the lateral ventricles and hence provide insight into the processes underlying post-developmental neurogenesis in the mammalian brain. PMID:25951750

  2. The role of cannabinoids in adult neurogenesis.

    PubMed

    Prenderville, Jack A; Kelly, Áine M; Downer, Eric J

    2015-08-01

    The processes underpinning post-developmental neurogenesis in the mammalian brain continue to be defined. Such processes involve the proliferation of neural stem cells and neural progenitor cells (NPCs), neuronal migration, differentiation and integration into a network of functional synapses within the brain. Both intrinsic (cell signalling cascades) and extrinsic (neurotrophins, neurotransmitters, cytokines, hormones) signalling molecules are intimately associated with adult neurogenesis and largely dictate the proliferative activity and differentiation capacity of neural cells. Cannabinoids are a unique class of chemical compounds incorporating plant-derived cannabinoids (the active components of Cannabis sativa), the endogenous cannabinoids and synthetic cannabinoid ligands, and these compounds are becoming increasingly recognized for their roles in neural developmental processes. Indeed, cannabinoids have clear modulatory roles in adult neurogenesis, probably through activation of both CB1 and CB2 receptors. In recent years, a large body of literature has deciphered the signalling networks involved in cannabinoid-mediated regulation of neurogenesis. This timely review summarizes the evidence that the cannabinoid system is intricately associated with neuronal differentiation and maturation of NPCs and highlights intrinsic/extrinsic signalling mechanisms that are cannabinoid targets. Overall, these findings identify the central role of the cannabinoid system in adult neurogenesis in the hippocampus and the lateral ventricles and hence provide insight into the processes underlying post-developmental neurogenesis in the mammalian brain. PMID:25951750

  3. Adult psychopathic personality with childhood-onset hyperactivity and conduct disorder: a central problem constellation in forensic psychiatry.

    PubMed

    Soderstrom, Henrik; Sjodin, Anna-Kari; Carlstedt, Anita; Forsman, Anders

    2004-01-01

    To describe lifetime mental disorders among perpetrators of severe inter-personal crimes and to identify the problem domains most closely associated with aggression and a history of repeated violent criminality, we used structured interviews, clinical assessments, analyses of intellectual functioning, medical and social files, and collateral interviews in 100 consecutive subjects of pretrial forensic psychiatric investigations. Childhood-onset neuropsychiatric disorders [attention-deficit/hyperactivity disorder (AD/HD), learning disability, tics and autism spectrum disorders] affected 55% of the subjects and formed complex comorbidity patterns with adult personality disorders [including psychopathic traits according to the Psychopathy Checklist (PCL-R)], mood disorders and substance abuse. The closest psychiatric covariates to high Lifetime History of Aggression (LHA) scores and violent recidivism were the PCL-R scores and childhood conduct disorder (CD). Behavioral and affective PCL-R factors were closely associated with childhood AD/HD, CD, and autistic traits. The results support the notion that childhood-onset social and behavioral problems form the most relevant psychiatric symptom cluster in relation to pervasive adult violent behavior, while late-onset mental disorders are more often associated with single acts of violent or sexual aggression. PMID:14675746

  4. Signaling through ERK1/2 controls myelin thickness during myelin repair in the adult central nervous system.

    PubMed

    Fyffe-Maricich, Sharyl L; Schott, Alexandra; Karl, Molly; Krasno, Janet; Miller, Robert H

    2013-11-20

    Oligodendrocytes, the myelin-forming cells of the CNS, exquisitely tailor the thickness of individual myelin sheaths to the diameter of their target axons to maximize the speed of action potential propagation, thus ensuring proper neuronal connectivity and function. Following demyelinating injuries to the adult CNS, newly formed oligodendrocytes frequently generate new myelin sheaths. Following episodes of demyelination such as those that occur in patients with multiple sclerosis, however, the matching of myelin thickness to axon diameter fails leaving remyelinated axons with thin myelin sheaths potentially compromising function and leaving axons vulnerable to damage. How oligodendrocytes determine the appropriate thickness of myelin for an axon of defined size during repair is unknown and identifying the signals that regulate myelin thickness has obvious therapeutic implications. Here, we show that sustained activation of extracellular-regulated kinases 1 and 2 (ERK1/2) in oligodendrocyte lineage cells results in accelerated myelin repair after injury, and is sufficient for the generation of thick myelin sheaths around remyelinated axons in the adult mouse spinal cord. Our findings suggest a model where ERK1/2 MAP kinase signaling acts as a myelin thickness rheostat that instructs oligodendrocytes to generate axon-appropriate quantities of myelin. PMID:24259565

  5. [Central diabetes insipidus in adult patients--the first sign of Langerhans cell histiocytosis and Erdheim-Chester disease. Three case studies and literature review].

    PubMed

    Adam, Z; Balsíková, K; Krejcí, M; Pour, L; Stĕpánková, S; Svacina, P; Hermanová, M; Vanícek, J; Krupa, P; Stanícek, J; Koukalová, R; Neubauer, J; Krivanová, A; Mayer, J; Hájek, R

    2010-02-01

    Central diabetes insipidus with an onset in adulthood is very rare. Unlike in children, central diabetes insipidus in adults is more frequently caused by inflammatory processes and neoplastic infiltrations that do not originate from the neuronal tissue than primary neuronal tissue tumours. Rare histiocytic neoplasias (Langerhans cell histiocytosis, xanthogranulomatosis and Erdheim-Chester disease) have a specific affinity to hypothalamus and the pituitary stalk not only in paediatric patients but also when occurring in adults. We describe 3 cases of central diabetes insipidus with an onset in adulthood. Diabetes insipidus was the first sign of Langerhans cell histiocytosis in 2 patients, and it was the first sign of Erdheim-Chester disease in one patient. MR imaging showed pathological infiltration and dilated pituitary stalks in all 3 patients. PET-CT proved useful in differential diagnosis, showing further extracranial pathological changes either on the basis of significant glucose accumulation or on the basis of CT imaging. The Langerhans cell histiocytosis in the first patient has also manifested itself as an infiltration of the perianal area with intensive accumulation of fluorodeoxyglucose (FDG) - SUV 8.6 and gingival inflammation indistinguishable from parodontosis. Histology of the perianal infiltrate confirmed Langerhans cell histiocytosis. Infiltration of the pituitary stalk disappeared from the MR image after 4 cycles of 2-chlordeoxyadenosin (5 mg/m2 5 consecutive days). The PET-CT of the 2nd patient showed only borderline accumulation of FDG in the ENT area, while simultaneously performed CT imaging showed cystic restructuring of the pulmonary parenchyma and nodulations consistent with pulmonary Langerhans cell histiocytosis. Bronchoalveolar lavage identified higher number of CD1 and S100 positive elements, consistent, once again, with pulmonary LCH also affecting pituitary stalk and ear canal. The PET-CT of the third patient showed increased activity

  6. Mammalian Wax Biosynthesis

    PubMed Central

    Cheng, Jeffrey B.; Russell, David W.

    2009-01-01

    Wax monoesters are synthesized by the esterification of fatty alcohols and fatty acids. A mammalian enzyme that catalyzes this reaction has not been isolated. We used expression cloning to identify cDNAs encoding a wax synthase in the mouse preputial gland. The wax synthase gene is located on the X chromosome and encodes a member of the acyltransferase family of enzymes that synthesize neutral lipids. Expression of wax synthase in cultured cells led to the formation of wax monoesters from straight chain saturated, unsaturated, and polyunsaturated fatty alcohols and acids. Polyisoprenols also were incorporated into wax monoesters by the enzyme. The wax synthase had little or no ability to synthesize cholesteryl esters, diacylglycerols, or triacylglycerols, whereas other acyltransferases, including the acyl-CoA:monoacylglycerol acyltransferase 1 and 2 enzymes and the acyl-CoA:diacylglycerol acyltransferase 1 and 2 enzymes, exhibited modest wax monoester synthesis activities. Confocal light microscopy indicated that the wax synthase was localized in membranes of the endoplasmic reticulum. Wax synthase mRNA was abundant in tissues rich in sebaceous glands such as the preputial gland and eyelid and was present at lower levels in other tissues. Coexpression of cDNAs specifying fatty acyl-CoA reductase 1 and wax synthase led to the synthesis of wax monoesters. The data suggest that wax monoester synthesis in mammals involves a two step biosynthetic pathway catalyzed by fatty acyl-CoA reductase and wax synthase enzymes. PMID:15220349

  7. Structure of mammalian metallothionein

    SciTech Connect

    Kaegi, J.H.R.; Vasak, M.; Lerch, K.; Gilg, D.E.O.; Hunziker, P.; Bernhard, W.R.; Good, M.

    1984-03-01

    All mammalian metallothioneins characterized contain a single polypeptide chain of 61 amino acid residues, among them 20 cysteines providing the ligands for seven metal-binding sites. Native metallothioneins are usually heterogeneous in metal composition, with Zn, Cd, and Cu occurring in varying proportions. However, forms containing only a single metal species, i.e., Zn, Cd, Ni, Co, Hg, Pb, Bi, have now been prepared by in vitro reconstitution from the metal-free apoprotein. By spectroscopic analysis of such derivatives it was established that all cysteine residues participate in metal binding, that each metal ion is bound to four thiolate ligands, and that the symmetry of each complex is close to that of a tetrahedron. To satisfy the requirements of the overall Me/sub 7/(Cys/sup -/)/sub 20/ stoichiometry, the complexes must be combined to form metal-thiolate cluster structures. The actual spatial organization of the clusters and the polypeptide chain remains to be established. An attractive possibility is the arrangement of the tetrahedral metal-thiolates in adamantane-like structures surrounded by properly folded segments of the chain providing the ligands. /sup 1/H-NMR data and infrared absorption measurements are consistent with a tightly folded structure rich in ..beta..-type conformation. 79 references, 11 figures, 4 tables.

  8. Chemosignals, Hormones and Mammalian Reproduction

    PubMed Central

    Petrulis, Aras

    2013-01-01

    Many mammalian species use chemosignals to coordinate reproduction by altering the physiology and behavior of both sexes. Chemosignals prime reproductive physiology so that individuals become sexually mature and active at times when mating is most probable and suppress it when it is not. Once in reproductive condition, odors produced and deposited by both males and females are used to find and select individuals for mating. The production, dissemination and appropriate responses to these cues are modulated heavily by organizational and activational effects of gonadal sex steroids and thereby intrinsically link chemical communication to the broader reproductive context. Many compounds have been identified as “pheromones” but very few have met the expectations of that term: a unitary, species-typical substance that is both necessary and sufficient for an experience-independent behavioral or physiological response. In contrast, most responses to chemosignals are dependent or heavily modulated by experience, either in adulthood or during development. Mechanistically, chemosignals are perceived by both main and accessory (vomeronasal) olfactory systems with the importance of each system tied strongly to the nature of the stimulus rather than to the response. In the central nervous system, the vast majority of responses to chemosignals are mediated by cortical and medial amygdala connections with hypothalamic and other forebrain structures. Despite the importance of chemosignals in mammals, many details of chemical communication differ even among closely related species and defy clear categorization. Although generating much research and public interest, strong evidence for the existence of a robust chemical communication among humans is lacking. PMID:23545474

  9. Mammalian Sirtuins and Energy Metabolism

    PubMed Central

    Li, Xiaoling; Kazgan, Nevzat

    2011-01-01

    Sirtuins are highly conserved NAD+-dependent protein deacetylases and/or ADP-ribosyltransferases that can extend the lifespan of several lower model organisms including yeast, worms and flies. The seven mammalian sirtuins, SIRT1 to SIRT7, have emerged as key metabolic sensors that directly link environmental signals to mammalian metabolic homeostasis and stress response. Recent studies have shed light on the critical roles of sirtuins in mammalian energy metabolism in response to nutrient signals. This review focuses on the involvement of two nuclear sirtuins, SIRT1 and SIRT6, and three mitochondrial sirtuins, SIRT3, SIRT4, and SIRT5, in regulation of diverse metabolic processes. PMID:21614150

  10. Is the intraosseous access route fast and efficacious compared to conventional central venous catheterization in adult patients under resuscitation in the emergency department? A prospective observational pilot study

    PubMed Central

    Leidel, Bernd A; Kirchhoff, Chlodwig; Bogner, Viktoria; Stegmaier, Julia; Mutschler, Wolf; Kanz, Karl-Georg; Braunstein, Volker

    2009-01-01

    Background For patients' safety reasons, current American Heart Association and European Resuscitation Council guidelines recommend intraosseous (IO) vascular access as an alternative in cases of emergency, if prompt venous catheterization is impossible. The purpose of this study was to compare the IO access as a bridging procedure versus central venous catheterization (CVC) for in-hospital adult emergency patients under resuscitation with impossible peripheral intravenous (IV) access. We hypothesised, that CVC is faster and more efficacious compared to IO access. Methods A prospective observational study comparing success rates and procedure times of IO access (EZ-IO, Vidacare Corporation) versus CVC in adult (≥18 years of age) patients under trauma and medical resuscitation admitted to our emergency department with impossible peripheral IV catheterization was conducted. Procedure time was defined from preparation and insertion of vascular access type until first drug or infusion solution administration. Success rate on first attempt and procedure time for each access route was evaluated and statistically tested. Results Ten consecutive adult patients under resuscitation, each receiving IO access and CVC, were analyzed. IO access was performed with 10 tibial or humeral insertions, CVC in 10 internal jugular or subclavian veins. The success rate on first attempt was 90% for IO insertion versus 60% for CVC. Mean procedure time was significantly lower for IO cannulation (2.3 min ± 0.8) compared to CVC (9.9 min ± 3.7) (p < 0.001). As for complications, failure of IO access was observed in one patient, while two or more attempts of CVC were necessary in four patients. No other relevant complications, like infection, bleeding or pneumothorax were observed. Conclusion Preliminary data demonstrate that IO access is a reliable bridging method to gain vascular access for in-hospital adult emergency patients under trauma or medical resuscitation with impossible

  11. Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals

    PubMed Central

    KANEKO-ISHINO, Tomoko; ISHINO, Fumitoshi

    2015-01-01

    Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is “mammalian-specific genomic functions”, a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of “mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons”, based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes. PMID:26666304

  12. Penetration of Treosulfan and its Active Monoepoxide Transformation Product into Central Nervous System of Juvenile and Young Adult Rats.

    PubMed

    Romański, Michał; Baumgart, Joachim; Böhm, Sonja; Główka, Franciszek K

    2015-12-01

    Treosulfan (TREO) is currently investigated as an alternative treatment of busulfan in conditioning before hematopoietic stem cell transplantation. The knowledge of the blood-brain barrier penetration of the drug is still scarce. In this paper, penetration of TREO and its active monoepoxide (S,S-EBDM) and diepoxide (S,S-DEB) into the CNS was studied in juvenile (JR) and young adult rats (YAR) for the first time. CD rats of both sexes (n = 96) received an intravenous dose of TREO 500 mg/kg b.wt. Concentrations of TREO, S,S-EBDM, and S,S-DEB in rat plasma, brain, and cerebrospinal fluid (CSF, in YAR only) were determined by validated bioanalytical methods. Pharmacokinetic calculations were performed in WinNonlin using a noncompartmental analysis and statistical evaluation was done in Statistica software. In male JR, female JR, male YAR, and female YAR, the brain/plasma area under the curve (AUC) ratio for unbound TREO was 0.14, 0.17, 0.10, and 0.07 and for unbound S,S-EBDM, it was 0.52, 0.48, 0.28, and 0.22, respectively. The CSF/plasma AUC ratio in male and female YAR was 0.12 and 0.11 for TREO and 0.66 and 0.64 for S,S-EBDM, respectively. Elimination rate constants of TREO and S,S-EBDM in all the matrices were sex-independent with a tendency to be lower in the JR. No quantifiable levels of S,S-DEB were found in the studied samples. TREO and S,S-EBDM demonstrated poor and sex-independent penetration into CNS. However, the brain exposure was greater in juvenile rats, so very young children might potentially be more susceptible to high-dose TREO-related CNS exposure than young adults. PMID:26428246

  13. A Common Phenotype Polymorphism in Mammalian Brains Defined by Concomitant Production of Prolactin and Growth Hormone

    PubMed Central

    Daude, Nathalie; Lee, Inyoul; Kim, Taek-Kyun; Janus, Christopher; Glaves, John Paul; Gapeshina, Hristina; Yang, Jing; Sykes, Brian D.; Carlson, George A.; Hood, Leroy E.; Westaway, David

    2016-01-01

    Pituitary Prolactin (PRL) and Growth Hormone (GH) are separately controlled and sub-serve different purposes. Surprisingly, we demonstrate that extra-pituitary expression in the adult mammalian central nervous system (CNS) is coordinated at mRNA and protein levels. However this was not a uniform effect within populations, such that wide inter-individual variation was superimposed on coordinate PRL/GH expression. Up to 44% of individuals in healthy cohorts of mice and rats showed protein levels above the norm and coordinated expression of PRL and GH transcripts above baseline occurred in the amygdala, frontal lobe and hippocampus of 10% of human subjects. High levels of PRL and GH present in post mortem tissue were often presaged by altered responses in fear conditioning and stress induced hyperthermia behavioral tests. Our data define a common phenotype polymorphism in healthy mammalian brains, and, given the pleiotropic effects known for circulating PRL and GH, further consequences of coordinated CNS over-expression may await discovery. PMID:26894278

  14. A Common Phenotype Polymorphism in Mammalian Brains Defined by Concomitant Production of Prolactin and Growth Hormone.

    PubMed

    Daude, Nathalie; Lee, Inyoul; Kim, Taek-Kyun; Janus, Christopher; Glaves, John Paul; Gapeshina, Hristina; Yang, Jing; Sykes, Brian D; Carlson, George A; Hood, Leroy E; Westaway, David

    2016-01-01

    Pituitary Prolactin (PRL) and Growth Hormone (GH) are separately controlled and sub-serve different purposes. Surprisingly, we demonstrate that extra-pituitary expression in the adult mammalian central nervous system (CNS) is coordinated at mRNA and protein levels. However this was not a uniform effect within populations, such that wide inter-individual variation was superimposed on coordinate PRL/GH expression. Up to 44% of individuals in healthy cohorts of mice and rats showed protein levels above the norm and coordinated expression of PRL and GH transcripts above baseline occurred in the amygdala, frontal lobe and hippocampus of 10% of human subjects. High levels of PRL and GH present in post mortem tissue were often presaged by altered responses in fear conditioning and stress induced hyperthermia behavioral tests. Our data define a common phenotype polymorphism in healthy mammalian brains, and, given the pleiotropic effects known for circulating PRL and GH, further consequences of coordinated CNS over-expression may await discovery. PMID:26894278

  15. Circulating kisspeptin levels exhibit sexual dimorphism in adults, are increased in obese prepubertal girls and do not suffer modifications in girls with idiopathic central precocious puberty.

    PubMed

    Pita, Jimena; Barrios, Vicente; Gavela-Pérez, Teresa; Martos-Moreno, Gabriel Á; Muñoz-Calvo, María T; Pozo, Jesús; Rovira, Adela; Argente, Jesús; Soriano-Guillén, Leandro

    2011-09-01

    The system KISS1-KISS1R is one of the main regulators of the hypothalamic-pituitary-gonadal axis and constitutes a link between metabolism and reproduction through its interaction with leptin. The aim of this study was to clarify the possible utility of kisspeptin as a pubertal marker and/or the possible influence of nutritional status in kisspeptin levels. To this end, we have studied kisspeptin plasma levels throughout sexual development and in prepubertal obese girls and girls affected by idiopathic central precocious puberty (CPP). Plasma kisspeptin concentrations were analyzed by RIA. An increase in kisspeptin levels was observed in adult females compared to healthy prepubertal and pubertal girls (p<0.001) and to adult males (p<0.001). Additionally, kisspeptin was increased in prepubertal obese girls compared to healthy prepubertal girls (p<0.01) and girls with idiopathic CPP (p<0.05). As revealed by the regression analysis, in prepubertal healthy and obese girls and girls with idiopathic CCP, the parameters that influenced kisspeptin levels were BMI (R(2)=0.10, p<0.05) and leptin levels (R(2)=0.14, p<0.01). In conclusion, kisspeptin levels do not seem to be a good pubertal marker. The results obtained in prepubertal and idiopathic CCP girls point to a relationship between leptin, BMI and kisspeptin at least in this group, and suggest a possible role for adipose tissue in the modulation kisspeptin synthesis. PMID:21827808

  16. Central Dogma Goes Digital.

    PubMed

    Lin, Yihan; Elowitz, Michael B

    2016-03-17

    In this issue of Molecular Cell, Tay and colleagues (Albayrak et al., 2016) describe a new technique to digitally quantify the numbers of protein and mRNA in the same mammalian cell, providing a new way to look at the central dogma of molecular biology. PMID:26990983

  17. The use of microdialysis for the study of drug kinetics: central nervous system pharmacokinetics of diphenhydramine in fetal, newborn, and adult sheep.

    PubMed

    Au-Yeung, Sam C S; Riggs, K Wayne; Gruber, Nancy; Rurak, Dan W

    2007-08-01

    The central nervous system (CNS) pharmacokinetics of the H(1) receptor antagonist diphenhydramine (DPHM) were studied in 100- and 120-day-old fetuses, 10- and 30-day-old newborn lambs, and adult sheep using in vivo microdialysis. DPHM was administered i.v. at five infusion rates, with each step lasting 7 h. In all ages, cerebrospinal fluid (CSF) and extracellular fluid (ECF) concentrations were very similar to each other, which suggests that DPHM between these two compartments is transferred by passive diffusion. In addition, the brain-to-plasma concentration ratios were >or=3 in all age groups, suggesting the existence of a transport process for DPHM into the brain. Both brain and plasma DPHM concentrations increased in a linear fashion over the dose range studied. However, the ECF/unbound plasma and CSF/unbound plasma DPHM concentration ratios were significantly higher in the fetus and lambs (approximately 5 to 6) than in the adult (approximately 3). The factors f(CSF) and f(ECF), the ratios of DPHM areas under the curves (AUCs) in CSF and ECF to the plasma DPHM AUC, respectively, decreased with age, indicating that DPHM is more efficiently removed from the brain with increasing age. The extent of plasma protein binding of the drug increased with age. This study provides evidence for a transporter-mediated mechanism for the influx of DPHM into the brain and also for an efflux transporter for the drug, whose activity increases with age. Moreover, the higher brain DPHM levels in the fetus and lamb compared with the adult may explain the greater CNS effects of the drug at these ages. PMID:17485495

  18. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993

    PubMed Central

    Lazarus, Hillard M.; Richards, Susan M.; Chopra, Raj; Litzow, Mark R.; Burnett, Alan K.; Wiernik, Peter H.; Franklin, Ian M.; Tallman, Martin S.; Cook, Lucy; Buck, Georgina; Durrant, I. Jill; Rowe, Jacob M.; Goldstone, Anthony H.

    2006-01-01

    Outcome of acute lymphoblastic leukemia (ALL) in adults with central nervous system (CNS) disease at diagnosis is unclear. We treated 1508 de novo ALL patients with 2-phase induction and then high-dose methotrexate with l-asparaginase. Patients up to 50 years old in first remission (CR1) with a matched related donor (MRD) underwent an allogeneic stem cell transplantation (SCT); the remainder in CR1 were randomized to an autologous SCT or intensive consolidation followed by maintenance chemotherapy. Philadelphia chromosome (Ph)–positive patients were offered a matched unrelated donor (MUD) allogeneic SCT. Seventy-seven of 1508 (5%) patients a median age of 29 years had CNS leukemia at presentation; 13 of the 77 (17%) had Ph-positive ALL. Sixty-nine of 77 (90%) patients attained CR1. Thirty-six patients underwent transplantation in CR1 (25 MRD, 5 MUD, and 6 autografts). Eleven of 25 patients with MRD transplantation remain alive at 21 to 102 months, 2 of 5 with MUD at 42 and 71 months, and 1 of 6 with autologous SCT at 35 months. Seven of 27 treated with consolidation/maintenance remain in CR1 56 to 137 months after diagnosis. Overall survival at 5 years was 29% in those with CNS involvement at diagnosis versus 38% (P = .03) for those without. CNS leukemia in adult ALL is uncommon at diagnosis. Adult Ph-negative ALL patients, however, can attain long-term disease-free survival using SCT as well as conventional chemotherapy. PMID:16556888

  19. Murine mesenchymal stem cells transplanted to the central nervous system of neonatal versus adult mice exhibit distinct engraftment kinetics and express receptors that guide neuronal cell migration.

    PubMed

    Phinney, Donald G; Baddoo, Melody; Dutreil, Maria; Gaupp, Dina; Lai, Wen Tzu; Isakova, Iryna A

    2006-06-01

    Mesenchymal stem cells (MSCs) have demonstrated efficacy as cellular vectors for treating a variety of nervous system disorders. Nevertheless, few studies have quantified MSC engraftment levels or explored the mechanisms that promote their survival and migration in nervous tissue. In this study, we compared the engraftment kinetics and anatomical distribution of murine, male MSCs injected intracranially into neonatal versus adult female mice using a real-time PCR assay that targets the mouse SRY gene. These analyses revealed that MSCs exhibited low but equivalent engraftment levels in the central nervous system (CNS) of neonatal and adult transplant recipients at 12 days post-injection. However, MSC engraftment levels were significantly greater at 60 and 150 days post-transplantation in neonates as compared to adults. Despite these differences, engrafted MSCs were widely distributed along the neuraxis of the CNS in both transplant groups. Collectively, these data indicate that proliferation, but not engraftment and migration, of MSCs in brain are regulated by the host microenvironment. Using a genomics approach, we also identified MSC subpopulations that express neural adhesion proteins and receptors that regulate neuronal cell migration in brain, including cadherin 2, neurexin 1, ninjurin 1, neogenin 1, neuropilin 2, and roundabout homolog 1 and 4. Functional studies indicate these proteins confer cell adhesion and migration of MSCs in response to the appropriate chemoattractant. On the basis of these findings, we conclude that the unique molecular composition of MSC subpopulations imparts to them an inherent capacity to engraft and migrate in brain. These subpopulations may represent more potent cellular vectors for treating CNS disorders. PMID:16846379

  20. Mammalian DNA Repair. Final Report

    SciTech Connect

    2003-01-24

    The Gordon Research Conference (GRC) on Mammalian DNA Repair was held at Harbortown Resort, Ventura Beach, CA. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  1. Mammalian Interphase Cdks

    PubMed Central

    2012-01-01

    Cyclin-dependent kinases (Cdks) drive cell cycle progression in all eukaryotes. Yeasts have a single major Cdk that mediates distinct cell cycle transitions via association with different cyclins. The closest homolog in mammals, Cdk1, drives mitosis. Mammals have additional Cdks—Cdk2, Cdk4, and Cdk6—that represent the major Cdks activated during interphase (iCdks). A large body of evidence has accrued that suggests that activation of iCdks dictates progression though interphase. In apparent contradiction, deficiency in each individual iCdk, respectively, in knockout mice proved to be compatible with live birth and in some instances fertility. Moreover, murine embryos could be derived with Cdk1 as the only functional Cdk. Thus, none of the iCdks is strictly essential for mammalian cell cycle progression, raising the possibility that Cdk1 is the dominant regulator in interphase. However, an absence of iCdks has been accompanied by major shifts in cyclin association to Cdk1, suggesting gain in function. After considerable tweaking, a chemical genetic approach has recently been able to examine the impact of acute inhibition of Cdk2 activity without marked distortion of cyclin/Cdk complex formation. The results suggest that, when expressed at its normal levels, Cdk2 performs essential roles in driving human cells into S phase and maintaining genomic stability. These new findings appear to have restored order to the cell cycle field, bringing it full circle to the view that iCdks indeed play important roles. They also underscore the caveat in knockdown and knockout approaches that protein underexpression can significantly perturb a protein interaction network. We discuss the implications of the new synthesis for future cell cycle studies and anti–Cdk-based therapy of cancer and other diseases. PMID:23634250

  2. Isotope Labeling in Mammalian Cells

    PubMed Central

    Dutta, Arpana; Saxena, Krishna; Klein-Seetharaman, Judith

    2011-01-01

    Isotope labeling of proteins represents an important and often required tool for the application of nuclear magnetic resonance (NMR) spectroscopy to investigate the structure and dynamics of proteins. Mammalian expression systems have conventionally been considered to be too weak and inefficient for protein expression. However, recent advances have significantly improved the expression levels of these systems. Here, we provide an overview of some of the recent developments in expression strategies for mammalian expression systems in view of NMR investigations. PMID:22167668

  3. Long-term exposure to twice-ambient ozone (O3) affects carbon sink strength, allocation and stem growth in adult central European forest trees

    NASA Astrophysics Data System (ADS)

    Grams, T. E.; Matyssek, R.

    2009-12-01

    Amongst air pollutants, ground-level ozone (O3) is potentially the most detrimental to vegetation. Spreading globally, enhanced O3 levels are predicted to increase, in particular, in rapidly developing countries and, thus, O3 must now be considered in climate change scenarios and post-Kyoto policies. Here, we present an appraisal of a unique 8-year free-air O3 fumigation experiment on adult European beech (Fagus sylvatica) and Noway spruce (Picea abies), ecologically and economically important, late-succession tree species in Central Europe. For the first time, whole-plant canopies of naturally grown, 60 to 70 years old forest trees were exposed to twice-ambient O3 levels for a total of eight years. Throughout the study period, enhanced O3 uptake in the elevated O3 treatment affected net C fixation and distinctly weakened the whole-stem growth in beech. In contrast, adult spruce at the same site did not display decline in stem biomass development. Those findings corroborate species-specific sensitivities to O3 reported from previous chamber studies on juvenile beech and spruce trees. Carbon allocation of adult trees, as a mechanistical basis of growth processes, was investigated through stable isotope tracer experiments using 13C depleted CO2 at the canopy level. To this end, a novel free-air CO2 exposure system, named tubeFACE, was developed, which employed micro-porous PVC tubes hanging through the canopy of adult trees. In a 19-day 13CO2/12CO2 labeling experiment, CO2 with a δ13C of -46.9 ‰ was continuously released into the canopy to increase [CO2] by 100 µmol mol-1, resulting in a reduction in δ13C of about 8 ‰. Subsequently, C allocation to respiratory pools of various tree organs was studied. Similar to the reduced stem growth in beech, elevated O3 significantly reduced allocation of labeled C to stem respiration, whereas in spruce such a reduction was not found. Hence, our study underlines the need to understand O3 risks by species, so that modeling

  4. A protocol for concurrent high-quality immunohistochemical and biochemical analyses in adult mouse central nervous system.

    PubMed

    Notter, Tina; Panzanelli, Patrizia; Pfister, Sandra; Mircsof, Dennis; Fritschy, Jean-Marc

    2014-01-01

    Biochemical analysis of central nervous system proteins and nucleic acids requires fresh-tissue homogenates, whereas immunohistochemistry usually is performed in sections prepared from perfusion-fixed tissue. Post-mortem immersion-fixation is possible, but largely impairs morphological preservation and protein antigenicity. Here, we present a simple, fast and versatile protocol allowing concurrent biochemical and immunohistochemical analysis, including pre-embedding immunoelectron microscopy, using tissue from the same animal. The protocol includes a brief transcardiac perfusion with ice-cold, oxygenated and glucose-supplemented artificial cerebrospinal fluid to maintain brain tissue alive, prior to isolation of regions of interest, followed by homogenisation for biochemistry or immersion-fixation for immunohistochemistry. We provide several examples demonstrating that this protocol allows optimal biochemical and morphological analysis, characterised with optimal sensitivity and preservation of tissue structure, along with a reduction of artefacts typically seen in perfusion-fixed tissue. This protocol should find widespread applications for combining analytical methods in tissue from the same animal, thereby reducing the number of mice required for a given experiment. PMID:24325300

  5. Expression of c-fos gene in central nervous system of adult medaka (Oryzias latipes) after hypergravity stimulation

    NASA Astrophysics Data System (ADS)

    Shimomura, S.; Ijiri, K.

    The immediate-early genes serve as useful neurobiological tools for mapping brain activity induced by a sensory stimulation. In this study, we have examined brain activity related to gravity perception of medaka (Oryzias latipes) by use of c-fos. The gene, which is homologous to the c-fos genes of other vertebrates, was identified in medaka. Functionally important domains are highly conserved among all the vertebrate species analyzed. Intraperitoneal administration of kainic acid transiently induced the c-fos mRNAs in medaka brain. The results indicate that the expression of c-fos can be utilized as a suitable anatomical marker for the increased neural activities in the central nervous system of medaka. Fish were continuously exposed to 3G hypergravity by centrifugation. Investigation of c-fos mRNA expression showed that c-fos mRNA significantly increased 30 minutes after a start of 3G exposure. The distribution of its transcripts within brains was analyzed by an in situ hybridization method. The 3G-treated medakas displayed c-fos positive cells in their brainstem regions, which are related to vestibular function, such as torus semicircularis, posterior octavu nucleus, nucleus tangentialis and inferior olive. Our results established the method to trace the activated area in the fish brain following gravity stimulation. The method will be a useful tool for understanding gravity perception in the brain.

  6. Calcium supplementation reverts central adiposity, leptin, and insulin resistance in adult offspring programed by neonatal nicotine exposure.

    PubMed

    Nobre, J L; Lisboa, P C; Santos-Silva, A P; Lima, N S; Manhães, A C; Nogueira-Neto, J F; Cabanelas, A; Pazos-Moura, C C; Moura, E G; de Oliveira, E

    2011-09-01

    Obesity is a worldwide epidemic. Calcium influences energy metabolism regulation, causing body weight loss. Because maternal nicotine exposure during lactation programs for obesity, hyperleptinemia, insulin resistance (IR), and hypothyroidism, we decided to evaluate the possible effect of dietary calcium supplementation on these endocrine dysfunctions in this experimental model. Osmotic minipumps containing nicotine solution (N: 6 mg/kg per day for 14 days) or saline (C) were s.c. implanted in lactating rats 2 days after giving birth (P2). At P120, N and C offspring were subdivided into four groups: 1) C - standard diet; 2) C with calcium supplementation (CCa, 10 g calcium carbonate/kg rat chow); 3) N - standard diet; and 4) N with calcium supplementation (NCa). Rats were killed at P180. As expected, N offspring showed higher visceral and total body fat, hyperleptinemia, lower hypothalamus leptin receptor (OB-R) content, hyperinsulinemia, and higher IR index. Also, higher tyrosine hydroxylase (TH) expression (+51%), catecholamine content (+37%), and serum 25-hydroxyvitamin D(3) (+76%) were observed in N offspring. Dietary calcium supplementation reversed adiposity, hyperleptinemia, OB-R underexpression, IR, TH overexpression, and vitamin D. However, this supplementation did not reverse hypothyroidism. In NCa offspring, Sirt1 mRNA was lower in visceral fat (-37%) and higher in liver (+42%). In conclusion, dietary calcium supplementation seems to revert most of the metabolic syndrome parameters observed in adult offspring programed by maternal nicotine exposure during lactation. It is conceivable that the reduction in fat mass per se, induced by calcium therapy, is the main mechanism that leads to the increment of insulin action. PMID:21680618

  7. Adult myeloid leukaemia, geology, and domestic exposure to radon and gamma radiation: a case control study in central Italy

    PubMed Central

    Forastiere, F.; Sperati, A.; Cherubini, G.; Miceli, M.; Biggeri, A.; Axelson, O.

    1998-01-01

    OBJECTIVES: To investigate whether indoor randon or gamma radiation might play a part in myeloid leukaemia as suggested by studies based on crude geographical or geological data for exposure assessment. METHODS: For six months randon and gamma radiation was measured with solid state nuclear track detectors and thermoluminescent dosimeters in dwellings of 44 adult male cases of acute myeloid leukaemia and 211 controls (all subjects deceased). Conditional logistic regression ORs (ORs) and 95% confidence intervals (95% CIs) were estimated for quartiles of radon and gamma radiation and for municipality and dwelling characteristics. RESULTS: The risk of leukaemia was associated with an increasing urbanisation index (p value for trend = 0.008). An increased OR was found among those living in more modern houses (OR 3.0, 95% CI 1.4 to 6.6). Confirming the findings of a previous study in the same area, geological features bore a positive association with myeloid leukemia, even by adjusting for level of urbanisation. Contrary to expectations from the previous study, however, no association appeared between myeloid leukaemia and radon and gamma radiation; for the highest quartiles of exposure, ORs were 0.56 (95% CI 0.2 to 1.4) and 0.52 (95% CI 0.2 to 1.4), respectively. Considering only subjects who had lived > or = 20 years in the monitored home and adjusting for urbanisation, there was still no effect of exposure to radiation. CONCLUSIONS: In view of the limited numbers, the results do not in general refute a possible risk of myeloid leukaemia from exposure to indoor radon or gamma radiation, but decrease the credibility of such a relation in the area studied and also of other studies suggesting an effect without monitoring indoor radiation. Some other fairly strong determinants have appeared--that is, level of urbanisation and living in modern houses-- that might need further consideration.   PMID:9614394

  8. Comparing measures of overall and central obesity in relation to cardiometabolic risk factors among US Hispanic/Latino adults

    PubMed Central

    Qi, Qibin; Strizich, Garrett; Hanna, David B.; Giacinto, Rebeca E.; Castañeda, Sheila F.; Sotres-Alvarez, Daniela; Pirzada, Amber; Llabre, Maria M.; Schneiderman, Neil; Aviles-Santa, Larissa; Kaplan, Robert C.

    2015-01-01

    Objective US Hispanics/Latinos have high prevalence of obesity and related comorbidities. We compared overall and central obesity measures in associations with cardiometabolic outcomes among US Hispanics/Latinos. Methods Multivariable regression assessed cross-sectional relationships of six obesity measures with cardiometabolic outcomes among 16,415 Hispanics/Latinos aged 18-74 years. Results BMI was moderately correlated with waist-to-hip ratio (WHR; women, r=0.37; men, r=0.58) and highly correlated with other obesity measures (r≥0.87) (P<0.0001). All measures of obesity were correlated with unfavorable levels of glycemic traits, blood pressure, and lipids, with similar r-estimates for each obesity measure (P<0.05). Multivariable-adjusted prevalence ratios (PRs) for diabetes (women, 6.7 [3.9, 11.5]; men, 3.9 [2.2, 6.9]), hypertension (women, 2.4 [1.9, 3.1]; men, 2.5 [1.9, 3.4]), and dyslipidemia (women, 2.1 [1.8, 2.4]; men, 2.2 [1.9, 2.6]) were highest for individuals characterized as overweight/obese (BMI≥25kg/m2) and abnormal WHR (women, ≥0.85; men, ≥0.90), compared to those with normal BMI and WHR (P<0.0001). Among normal-weight individuals, abnormal WHR was associated with increased cardiometabolic condition prevalence (P<0.05), particularly diabetes (women, PR=4.0 [2.2, 7.1]; men, PR=3.0 [1.6, 5.7]). Conclusions Obesity measures were associated with cardiometabolic risk factors to a similar degree in US Hispanics/Latinos. WHR is useful to identify individuals with normal BMI at increased cardiometabolic risk. PMID:26260150

  9. Adult Asylum Seekers from the Middle East Including Syria in Central Europe: What Are Their Health Care Problems?

    PubMed Central

    Pfortmueller, Carmen Andrea; Schwetlick, Miriam; Mueller, Thomas; Lehmann, Beat; Exadaktylos, Aristomenis Konstantinos

    2016-01-01

    Background Forced displacement related to persecution and violent conflict has reached a new peak in recent years. The primary aim of this study is to provide an initial overview of the acute and chronic health care problems of asylum seekers from the Middle East, with special emphasis on asylum seekers from Syria. Methods Our retrospective data analysis comprised adult patients presenting to our emergency department between 01.11.2011 and 30.06.2014 with the official resident status of an “asylum seeker” or “refugee” from the Middle East. Results In total, 880 patients were included in the study. Of these, 625 (71.0%) were male and 255 (29.0%) female. The median age was 34 (range 16–84). 222 (25.2%) of our patients were from Syria. The most common reason for presentation was surgical (381, 43.3%), followed by medical (321, 36.5%) and psychiatric (137, 15.6%). In patients with surgical presentations, trauma-related problems were most common (n = 196, 50.6%). Within the group of patients with medical presentation, acute infectious diseases were most common (n = 141, 43.9%), followed by neurological problems (n = 70, 21.8%) and gastrointestinal problems (n = 47, 14.6%). There were no differences between Syrian and non-Syrian refugees concerning surgical or medical admissions. The most common chronic disorder of unclear significance was chronic gastrointestinal problems (n = 132, 15%), followed by chronic musculoskeletal problems (n = 108, 12.3%) and chronic headaches (n = 78, 8.9%). Patients from Syria were significantly younger and more often suffered from a post-traumatic stress disorder than patients of other nationalities (p<0.0001, and p = 0.05, respectively). Conclusion Overall a remarkable number of our very young group of patients suffered from psychiatric disorders and unspecified somatic symptoms. Asylum seekers should be carefully evaluated when presenting to a medical facility and physicians should be aware of the high incidence of unspecified

  10. Employment of adult mammalian primary cells in toxicology: In vivo and in vitro genotoxic effects of environmentally significant N-nitrosodialkylamines in cells of the liver, lung, and kidney

    SciTech Connect

    Pool, B.L.; Brendler, S.Y.; Liegibel, U.M.; Schmezer, P. ); Tompa, A. )

    1990-01-01

    This report focuses on the use of freshly isolated primary mammalian cells from different tissues and organs of the rat for the rapid and efficient analysis of toxic and genotoxic chemicals. The cells are either treated in vitro or they are isolated from treated animals. Viability by trypan blue exclusion and DNA damage as single-strand breaks are monitored in either case. Therefore, it is possible to compare in vitro and in vivo results directly. N-nitrosamines with unique organ-specific modes in carcinogenesis were studied in vitro using hepatocytes derived from three species (rat, hamster, and pig) and in rat lung and kidney cells. The sensitive detection of all carcinogenic nitrosamines was achieved, although a pattern of cell-specific activation was not observable. The new modification of the in vivo approach allowed the sensitive detection of NDMA genotoxicity in hepatic and in extrahepatic tissues. It is important to point out that the method is an efficient tool for toxicokinetic studies with genotoxic carcinogens in vivo.

  11. Focusing on RISC assembly in mammalian cells

    SciTech Connect

    Hong Junmei; Wei Na; Chalk, Alistair; Wang Jue; Song, Yutong; Yi Fan; Qiao Renping; Sonnhammer, Erik L.L.; Wahlestedt, Claes; Liang Zicai Du, Quan

    2008-04-11

    RISC (RNA-induced silencing complex) is a central protein complex in RNAi, into which a siRNA strand is assembled to become effective in gene silencing. By using an in vitro RNAi reaction based on Drosophila embryo extract, an asymmetric model was recently proposed for RISC assembly of siRNA strands, suggesting that the strand that is more loosely paired at its 5' end is selectively assembled into RISC and results in target gene silencing. However, in the present study, we were unable to establish such a correlation in cell-based RNAi assays, as well as in large-scale RNAi data analyses. This suggests that the thermodynamic stability of siRNA is not a major determinant of gene silencing in mammalian cells. Further studies on fork siRNAs showed that mismatch at the 5' end of the siRNA sense strand decreased RISC assembly of the antisense strand, but surprisingly did not increase RISC assembly of the sense strand. More interestingly, measurements of melting temperature showed that the terminal stability of fork siRNAs correlated with the positions of the mismatches, but not gene silencing efficacy. In summary, our data demonstrate that there is no definite correlation between siRNA stability and gene silencing in mammalian cells, which suggests that instead of thermodynamic stability, other features of the siRNA duplex contribute to RISC assembly in RNAi.

  12. Sirtuins: Guardians of Mammalian Healthspan

    PubMed Central

    Giblin, William; Skinner, Mary E.; Lombard, David B.

    2014-01-01

    The first link between sirtuins and longevity was made 15 years ago in yeast. These initial studies sparked efforts by many laboratories working in diverse model organisms to elucidate the relationships between sirtuins, lifespan, and age-associated dysfunction. Here we discuss the current understanding of how sirtuins relate to aging. We focus primarily on mammalian sirtuins SIRT1, SIRT3, and SIRT6, the three sirtuins for which the most relevant data are available. Strikingly, a large body of evidence now indicates that these and other mammalian sirtuins suppress a variety of age-related pathologies and promote healthspan. Moreover, increased expression of SIRT1 or SIRT6 extends mouse lifespan. Overall, these data point to important roles for sirtuins in promoting mammalian health, and perhaps in modulating the aging process. PMID:24877878

  13. Electroporation into Cultured Mammalian Embryos

    NASA Astrophysics Data System (ADS)

    Nomura, Tadashi; Takahashi, Masanori; Osumi, Noriko

    Over the last century, mammalian embryos have been used extensively as a common animal model to investigate fundamental questions in the field of developmental biology. More recently, the establishment of transgenic and gene-targeting systems in laboratory mice has enabled researchers to unveil the genetic mechanisms under lying complex developmental processes (Mak, 2007). However, our understanding of cell—cell interactions and their molecular basis in the early stages of mammalian embryogenesis is still very fragmentary. One of the major problems is the difficulty of precise manipulation and limited accessibility to mammalian embryos via uterus wall. Unfortunately, existing tissue and organotypic culture systems per se do not fully recapitulate three-dimensional, dynamic processes of organogenesis observed in vivo. Although transgenic animal technology and virus-mediated gene delivery are useful to manipulate gene expression, these techniques take much time and financial costs, which limit their use.

  14. Mammalian homologues of the Drosophila eye specification genes.

    PubMed

    Hanson, I M

    2001-12-01

    The Drosophila compound eye is specified by the simultaneous and interdependent activity of transcriptional regulatory genes from four families: PAX6 (eyeless, twin of eyeless, eyegone), EYA (eyes absent), SIX (sine oculis, Optix) and DACH (dachshund). Mammals have homologues of all these genes, and many of them are expressed in the embryonic or adult eye, but the functional relationships between them are currently much less clear than in Drosophila. Nevertheless, mutations in the mammalian genes highlight their requirement both within and outside the eye in embryos and adults, and emphasize that they can be deployed in many different contexts. PMID:11735383

  15. Evolution of the mammalian dentate gyrus.

    PubMed

    Hevner, Robert F

    2016-02-15

    The dentate gyrus (DG), a part of the hippocampal formation, has important functions in learning, memory, and adult neurogenesis. Compared with homologous areas in sauropsids (birds and reptiles), the mammalian DG is larger and exhibits qualitatively different phenotypes: 1) folded (C- or V-shaped) granule neuron layer, concave toward the hilus and delimited by a hippocampal fissure; 2) nonperiventricular adult neurogenesis; and 3) prolonged ontogeny, involving extensive abventricular (basal) migration and proliferation of neural stem and progenitor cells (NSPCs). Although gaps remain, available data indicate that these DG traits are present in all orders of mammals, including monotremes and marsupials. The exception is Cetacea (whales, dolphins, and porpoises), in which DG size, convolution, and adult neurogenesis have undergone evolutionary regression. Parsimony suggests that increased growth and convolution of the DG arose in stem mammals concurrently with nonperiventricular adult hippocampal neurogenesis and basal migration of NSPCs during development. These traits could all result from an evolutionary change that enhanced radial migration of NSPCs out of the periventricular zones, possibly by epithelial-mesenchymal transition, to colonize and maintain nonperiventricular proliferative niches. In turn, increased NSPC migration and clonal expansion might be a consequence of growth in the cortical hem (medial patterning center), which produces morphogens such as Wnt3a, generates Cajal-Retzius neurons, and is regulated by Lhx2. Finally, correlations between DG convolution and neocortical gyrification (or capacity for gyrification) suggest that enhanced abventricular migration and proliferation of NSPCs played a transformative role in growth and folding of neocortex as well as archicortex. PMID:26179319

  16. The Planar Cell Polarity Transmembrane Protein Vangl2 Promotes Dendrite, Spine and Glutamatergic Synapse Formation in the Mammalian Forebrain.

    PubMed

    Okerlund, Nathan D; Stanley, Robert E; Cheyette, Benjamin N R

    2016-07-01

    The transmembrane protein Vangl2, a key regulator of the Wnt/planar cell polarity (PCP) pathway, is involved in dendrite arbor elaboration, dendritic spine formation and glutamatergic synapse formation in mammalian central nervous system neurons. Cultured forebrain neurons from Vangl2 knockout mice have simpler dendrite arbors, fewer total spines, less mature spines and fewer glutamatergic synapse inputs on their dendrites than control neurons. Neurons from mice heterozygous for a semidominant Vangl2 mutation have similar but not identical phenotypes, and these phenotypes are also observed in Golgi-stained brain tissue from adult mutant mice. Given increasing evidence linking psychiatric pathophysiology to these subneuronal sites and structures, our findings underscore the relevance of core PCP proteins including Vangl2 to the underlying biology of major mental illnesses and their treatment. PMID:27606324

  17. DNA repair in mammalian embryos.

    PubMed

    Jaroudi, Souraya; SenGupta, Sioban

    2007-01-01

    Mammalian cells have developed complex mechanisms to identify DNA damage and activate the required response to maintain genome integrity. Those mechanisms include DNA damage detection, DNA repair, cell cycle arrest and apoptosis which operate together to protect the conceptus from DNA damage originating either in parental gametes or in the embryo's somatic cells. DNA repair in the newly fertilized preimplantation embryo is believed to rely entirely on the oocyte's machinery (mRNAs and proteins deposited and stored prior to ovulation). DNA repair genes have been shown to be expressed in the early stages of mammalian development. The survival of the embryo necessitates that the oocyte be sufficiently equipped with maternal stored products and that embryonic gene expression commences at the correct time. A Medline based literature search was performed using the keywords 'DNA repair' and 'embryo development' or 'gametogenesis' (publication dates between 1995 and 2006). Mammalian studies which investigated gene expression were selected. Further articles were acquired from the citations in the articles obtained from the preliminary Medline search. This paper reviews mammalian DNA repair from gametogenesis to preimplantation embryos to late gestational stages. PMID:17141556

  18. Overall and abdominal obesity indicators had different association with central arterial stiffness and hemodynamics independent of age, sex, blood pressure, glucose, and lipids in Chinese community-dwelling adults

    PubMed Central

    Fu, Shihui; Luo, Leiming; Ye, Ping; Liu, Yuan; Zhu, Bing; Zheng, Jin; Bai, Yongyi; Bai, Jie

    2013-01-01

    Objective Limited large sample studies have specially compared overall and abdominal obesity in relation to central arterial stiffness and hemodynamics in community-dwelling adults, especially in the People’s Republic of China. This study aimed to compare the relationship between an overall obesity indicator (body mass index [BMI]), an abdominal obesity index (waist circumference [WC]), and central arterial stiffness and hemodynamics, independent of age, sex, blood pressure, glucose, and lipids, in Chinese community-dwelling adults. Methods For 2,624 adults in this study, anthropometric indices, such as BMI and WC, were measured. Central arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV). Central hemodynamics was represented by central pulse pressure (cPP). Results Both overall and abdominally obese adults were older, with significantly higher cfPWV, cPP, peripheral pulse pressure (pPP), fasting blood glucose (FBG), and low-density lipoprotein-cholesterol (LDL-C), and significantly lower high-density lipoprotein-cholesterol (HDL-C). After adjusting for age and sex, both the overall and abdominally obese individuals had independently higher pPP, FBG, and LDL-C levels, and lower HDL-C level. The overall obese individuals had independently higher cPP, but not cfPWV, after adjusting for age and sex, while the abdominally obese individuals had independently higher cfPWV, but not cPP. After adjusting for age, sex, pPP, FBG, LDL-C, and HDL-C, WC, but not BMI, was independently correlated with cfPWV, and BMI, but not WC, was independently associated with cPP. Age, sex, pPP, FBG, and HDL-C levels have independent association with cfPWV. Age, sex, pPP, but not FBG and HDL-C levels, have independent association with cPP. Conclusion The abdominal obesity index (WC), rather than the overall obesity indicator (BMI), was related to central arterial stiffness, independent of age, sex, blood pressure, glucose and lipids, while the overall obesity

  19. Physiological, pathological, and engineered cell identity reprogramming in the central nervous system.

    PubMed

    Smith, Derek K; Wang, Lei-Lei; Zhang, Chun-Li

    2016-07-01

    Multipotent neural stem cells persist in restricted regions of the adult mammalian central nervous system. These proliferative cells differentiate into diverse neuron subtypes to maintain neural homeostasis. This endogenous process can be reprogrammed as a compensatory response to physiological cues, traumatic injury, and neurodegeneration. In addition to innate neurogenesis, recent research has demonstrated that new neurons can be engineered via cell identity reprogramming in non-neurogenic regions of the adult central nervous system. A comprehensive understanding of these reprogramming mechanisms will be essential to the development of therapeutic neural regeneration strategies that aim to improve functional recovery after injury and neurodegeneration. WIREs Dev Biol 2016, 5:499-517. doi: 10.1002/wdev.234 For further resources related to this article, please visit the WIREs website. PMID:27258392

  20. High-Sensitivity C-Reactive Protein is Related to Central Obesity and the Number of Metabolic Syndrome Components in Jamaican Young Adults

    PubMed Central

    Bennett, Nadia R.; Ferguson, Trevor S.; Bennett, Franklyn I.; Tulloch-Reid, Marshall K.; Younger-Coleman, Novie O. M.; Jackson, Maria D.; Samms-Vaughan, Maureen E.; Wilks, Rainford J.

    2014-01-01

    Background: High-sensitivity C-reactive protein (hsCRP) has been shown to predict cardiovascular disease (CVD) endpoints and is associated with CVD risk factors and the metabolic syndrome. This study evaluated the association between hsCRP and CVD risk factors among Afro-Caribbean young adults in Jamaica. Methods: We conducted a cross-sectional analysis of data from the Jamaica 1986 Birth Cohort Study. Data were collected between 2005 and 2007 when participants were 18–20 years old. All participants completed an interviewer administered questionnaire and had anthropometric and blood pressure (BP) measurements performed. Fasting blood samples were collected for measurement of glucose, lipids, and hsCRP. Logistic regression models were used to identify factors independently associated with high hsCRP. Results: Analyses included 342 men and 404 women with mean age 18.8 ± 0.6 years. Approximately 15% of the participants had high risk hsCRP (>3 mg/L), with a higher prevalence among women (20 vs. 9%; p < 0.001). The prevalence of elevated hsCRP increased with body mass index category, high waist circumference (WC), high triglycerides, low high density lipoprotein, and lower parental education among women, but only for high WC and lower parental education among men. In logistic regression models controlling for sex and parental education, high WC was associated with significantly higher odds of high hsCRP (OR 7.8, 95% CI 4.8–12.9, p < 0.001). In a similar model, high hsCRP was also associated with the number of metabolic syndrome components. Compared to participants with no metabolic syndrome component, having one metabolic syndrome component was associated with a twofold higher odds of high hsCRP (OR 2.2, 95% CI 1.3–3.8, p = 0.005), while having three components was associated with a 14-fold higher odds of high hsCRP (OR 13.5, 95% CI 2.4–76.0, p < 0.001). Conclusion: High hsCRP is common among Jamaican young adults and is strongly

  1. Central corneal thickness, intraocular pressure, and degree of myopia in an adult myopic population aged 20 to 40 years in southeast Spain: determination and relationships

    PubMed Central

    Garcia-Medina, Manuel; Garcia-Medina, Jose Javier; Garrido-Fernandez, Pablo; Galvan-Espinosa, Jose; Martin-Molina, Jesus; Garcia-Maturana, Carlos; Perez-Pardo, Sergio; Pinazo-Duran, Maria Dolores

    2011-01-01

    Objective: To determine the values of, and study the relationships among, central corneal thickness (CCT), intraocular pressure (IOP), and degree of myopia (DM) in an adult myopic population aged 20 to 40 years in Almeria (southeast Spain). To our knowledge this is first study of this kind in this region. Methods: An observational, descriptive, cross-sectional study was done in which a sample of 310 myopic patients (620 eyes) aged 20 to 40 years was selected by gender- and age-stratified sampling, which was proportionally fixed to the size of the population strata for which a 20% prevalence of myopia, 5% epsilon, and a 95% confidence interval were hypothesized. We studied IOP, CCT, and DM and their relationships by calculating the mean, standard deviation, 95% confidence interval for the mean, median, Fisher’s asymmetry coefficient, range (maximum, minimum), and the Brown-Forsythe’s robust test for each variable (IOP, CCT, and DM). Results: In the adult myopic population of Almeria aged 20 to 40 years (mean of 29.8), the mean overall CCT was 550.12 μm. The corneas of men were thicker than those of women (P = 0.014). CCT was stable as no significant differences were seen in the 20- to 40-year-old subjects’ CCT values. The mean overall IOP was 13.60 mmHg. Men had a higher IOP than women (P = 0.002). Subjects over 30 years (13.83) had a higher IOP than those under 30 (13.38) (P = 0.04). The mean overall DM was −4.18 diopters. Men had less myopia than women (P < 0.001). Myopia was stable in the 20- to 40-year-old study population (P = 0.089). A linear relationship was found between CCT and IOP (R2 = 0.152, P ≤ 0.001). CCT influenced the IOP value by 15.2%. However no linear relationship between DM and IOP, or between CCT and DM, was found. Conclusions: CCT was found to be similar to that reported in other studies in different populations. IOP tends to increase after the age of 30 and is not accounted for by alterations in CCT values. PMID:21468330

  2. Viral Aetiology of Central Nervous System Infections in Adults Admitted to a Tertiary Referral Hospital in Southern Vietnam over 12 Years

    PubMed Central

    Tan, Le Van; Thai, Le Hong; Phu, Nguyen Hoan; Nghia, Ho Dang Trung; Chuong, Ly Van; Sinh, Dinh Xuan; Phong, Nguyen Duy; Mai, Nguyen Thi Hoang; Man, Dinh Nguyen Huy; Hien, Vo Minh; Vinh, Nguyen Thanh; Day, Jeremy; Chau, Nguyen Van Vinh; Hien, Tran Tinh; Farrar, Jeremy; de Jong, Menno D.; Thwaites, Guy; van Doorn, H. Rogier; Chau, Tran Thi Hong

    2014-01-01

    Background Central nervous system (CNS) infections are important diseases in both children and adults worldwide. The spectrum of infections is broad, encompassing bacterial/aseptic meningitis and encephalitis. Viruses are regarded as the most common causes of encephalitis and aseptic meningitis. Better understanding of the viral causes of the diseases is of public health importance, in order to better inform immunization policy, and may influence clinical management. Methodology/Principal Findings Study was conducted at the Hospital for Tropical Diseases in Ho Chi Minh City, a primary, secondary, and tertiary referral hospital for all southern provinces of Vietnam. Between December 1996 and May 2008, patients with CNS infections of presumed viral origin were enrolled. Laboratory diagnostics consisted of molecular and serological tests targeted at 14 meningitis/encephalitis-associated viruses. Of 291 enrolled patients, fatal outcome and neurological sequelae were recorded in 10% (28/291) and 27% (78/291), respectively. Mortality was especially high (9/19, 47%) amongst those with confirmed herpes simplex encephalitis which is attributed to the limited availability of intravenous acyclovir/valacyclovir. Japanese encephalitis virus, dengue virus, herpes simplex virus, and enteroviruses were the most common viruses detected, responsible for 36 (12%), 19 (6.5%), 19 (6.5%) and 8 (2.7%) respectively, followed by rubella virus (6, 2%), varicella zoster virus (5, 1.7%), mumps virus (2, 0.7%), cytomegalovirus (1, 0.3%), and rabies virus (1, 0.3%). Conclusions/Significance Viral infections of the CNS in adults in Vietnam are associated with high morbidity and mortality. Despite extensive laboratory testing, 68% of the patients remain undiagnosed. Together with our previous reports, the data confirm that Japanese encephalitis virus, dengue virus, herpes simplex virus, and enteroviruses are the leading identified causes of CNS viral infections in Vietnam, suggest that the

  3. An analysis of the epidemiological and etiological factors of oral tumors of young adults in a Central-Eastern European population.

    PubMed

    Túri, K; Barabás, P; Csurgay, K; Léhner, G Y; Lőrincz, A; Németh, Z S

    2013-07-01

    The etiology of tumors in young age is not precisely known yet, but studies on the topic generally agree that in this group of patients the traditionally known behavioural risk factors (tobacco and alcohol abuse) play no or a significantly less important role. Oral squamous cell carcinoma occurring at a young age is a topic of utmost importance that is extensively and intensively researched as, while the overall incidence of oral cancer is decreasing worldwide, that of squamous cell carcinoma diagnosed in young adults is steadily increasing. The present article aims at presenting the main questions and characteristics of tumors in young adults in Central-Eastern Europe and in developed West European countries as contrasted to tumors found in middle aged and elderly patients. Factors influencing the development of oral cancer include regulatory factors of the cell cycle, the inherited vulnerability of the genetic code of certain proteins and the presence of HPV infection with an oncogenic genotype. The connections of HPV infection and genetic damages are studied intensively. It is known that the prevalence of oral HPV infections is growing with a background of potentially changing sexual habits. It is debated, however, whether smoking and alcohol consumption could have a connection to HPV associated oral cancer and whether the spread of HPV in itself could be an explanation for the growing occurrence of young-age tumors. There is no consensus in the literature as to the prognostic significance of age. Some research groups have found a better life expectancy for young patients, while other authors found a worse prognosis for these patients. It is known that the prognosis of head and neck tumors, the prevalence of HPV infections as well as genetic mutations show regional and ethnic variations. This might be explained by differences in the degree of development of a preventive system, in the quality of care and in the attitudes of young patients towards visiting a

  4. Mammalian embryonic cerebrospinal fluid proteome has greater apolipoprotein and enzyme pattern complexity than the avian proteome.

    PubMed

    Parada, Carolina; Gato, Angel; Bueno, David

    2005-01-01

    During early stages of embryo development, the brain cavity is filled with Embryonic Cerebro-Spinal Fluid, which has an essential role in the survival, proliferation and neurogenesis of the neuroectodermal stem cells. We identified and analyzed the proteome of Embryonic Cerebro-Spinal Fluid from rat embryos (Rattus norvegicus), which includes proteins involved in the regulation of Central Nervous System development. The comparison between mammalian and avian Embryonic Cerebro-Spinal Fluid proteomes reveals great similarity, but also greater complexity in some protein groups. The pattern of apolipoproteins and enzymes in CSF is more complex in the mammals than in birds. This difference may underlie the greater neural complexity and synaptic plasticity found in mammals. Fourteen Embryonic Cerebro-Spinal Fluid gene products were previously identified in adult human Cerebro-Spinal Fluid proteome, and interestingly they are altered in patients with neurodegenerative diseases and/or neurological disorders. Understanding these molecules and the mechanisms they control during embryonic neurogenesis may contribute to our understanding of Central Nervous System development and evolution, and these human diseases. PMID:16335996

  5. When Herbivores Eat Predators: Predatory Insects Effectively Avoid Incidental Ingestion by Mammalian Herbivores

    PubMed Central

    Ben-Ari, Matan; Inbar, Moshe

    2013-01-01

    The direct trophic links between mammalian herbivores and plant-dwelling insects have been practically ignored. Insects are ubiquitous on plants consumed by mammalian herbivores and are thus likely to face the danger of being incidentally ingested by a grazing mammal. A few studies have shown that some herbivorous hemipterans are able to avoid this peril by dropping to the ground upon detecting the heat and humidity on the mammal's breath. We hypothesized that if this risk affects the entire plant-dwelling insect community, other insects that share this habitat are expected to develop similar escape mechanisms. We assessed the ability of three species (adults and larvae) of coccinellid beetles, important aphid predators, to avoid incidental ingestion. Both larvae and adults were able to avoid incidental ingestion effectively by goats by dropping to the ground, demonstrating the importance of this behavior in grazed habitats. Remarkably, all adult beetles escaped by dropping off the plant and none used their functional wings to fly away. In controlled laboratory experiments, we found that human breath caused 60–80% of the beetles to drop. The most important component of mammalian herbivore breath in inducing adult beetles and larvae to drop was the combination of heat and humidity. The fact that the mechanism of dropping in response to mammalian breath developed in distinct insect orders and disparate life stages accentuates the importance of the direct influence of mammalian herbivores on plant-dwelling insects. This direct interaction should be given its due place when discussing trophic interactions. PMID:23424674

  6. Impact of Cranial Irradiation Added to Intrathecal Conditioning in Hematopoietic Cell Transplantation in Adult Acute Myeloid Leukemia With Central Nervous System Involvement

    SciTech Connect

    Mayadev, Jyoti S.; Douglas, James G.; Storer, Barry E.; Appelbaum, Frederick R.; Storb, Rainer

    2011-05-01

    Purpose: Neither the prognostic importance nor the appropriate management of central nervous system (CNS) involvement is known for patients with acute myeloid leukemia (AML) undergoing hematopoietic cell transplantation (HCT). We examined the impact of a CNS irradiation boost to standard intrathecal chemotherapy (ITC). Methods and Materials: From 1995 to 2005, a total of 648 adult AML patients received a myeloablative HCT: 577 patients were CNS negative (CNS-), and 71 were CNS positive (CNS+). Of the 71 CNS+ patients, 52 received intrathecal chemotherapy alone (CNS+ITC), and 19 received ITC plus an irradiation boost (CNS+RT). Results: The CNS-, CNS+ITC, and CNS+RT patients had 1- and 5-year relapse-free survivals (RFS) of 43% and 35%, 15% and 6%, and 37% and 32%, respectively. CNS+ITC patients had a statistically significant worse RFS compared with CNS- patients (hazard ratio [HR], 2.65; 95% confidence interval [CI], 2.0-3.6; p < 0.0001). CNS+RT patients had improved relapse free survival over that of CNS+ITC patients (HR, 0.45; 95% CI, 0.2-0.8; p = 0.01). The 1- and 5-year overall survivals (OS) of patients with CNS-, CNS+ITC, and CNS+RT, were 50% and 38%, 21% and 6%, and 53% and 42%, respectively. The survival of CNS+RT were significantly better than CNS+ITC patients (p = 0.004). After adjusting for known risk factors, CNS+RT patients had a trend toward lower relapse rates and reduced nonrelapse mortality. Conclusions: CNS+ AML is associated with a poor prognosis. The role of a cranial irradiation boost to intrathecal chemotherapy appears to mitigate the risk of CNS disease, and needs to be further investigated to define optimal treatment strategies.

  7. A hospital-based study on knowledge and attitude related to vitiligo among adults visiting a tertiary health facility of central India

    PubMed Central

    Asati, Dinesh Prasad; Gupta, C. M.; Tiwari, Shreyansh; Kumar, Sanjeev; Jamra, Vishal

    2016-01-01

    Background: Vitiligo is one of the common stigmatizing dermatosis in the Indian society and the vitiligo patients have to face significant psychological hurt and social neglect. The severity of the stigma is related to the society's attitude and knowledge about it. Aims and Objectives: To document the prevalent knowledge and attitude in general public towards vitiligo patients, and to identify the determinants of good/poor knowledge and attitude. Materials and Methods: A systematic random sampling technique was adopted to enroll 700 adult participants visiting an urban tertiary healthcare facility of central India. We developed a questionnaire to collect information on knowledge and attitude of the participants. A composite score was developed for good knowledge and attitude and performance of the participants was compared with the selected determinants. Data analysis was conducted by Stata software version 11. Results: The overall knowledge score was good for 66.3% (95% confidence interval [CI]: 62.8%, 69.8%) of the participants. However, the score for attitude was comparatively poor i.e., only 16.9% (95% CI: 13.9%, 19.5%). None of the studied parameters could be significantly correlated with the knowledge score. Being married and being engaged in a health care related occupation were significant predictors of good attitude levels with P = 0.042 and 0.034 respectively, whereas female gender was the significant predictor for poor attitude with an odds ratio of 0.54 (95% CI: 0.33, 0.9) and P = 0.018. Conclusions: There were widespread myths prevalent about vitiligo in the studied population. The knowledge scores were better than attitude scores. PMID:27003965

  8. Mechanisms of mammalian iron homeostasis

    PubMed Central

    Pantopoulos, Kostas; Porwal, Suheel Kumar; Tartakoff, Alan; Devireddy, L.

    2012-01-01

    Iron is vital for almost all organisms because of its ability to donate and accept electrons with relative ease. It serves as a cofactor for many proteins and enzymes necessary for oxygen and energy metabolism, as well as for several other essential processes. Mammalian cells utilize multiple mechanisms to acquire iron. Disruption of iron homeostasis is associated with various human diseases: iron deficiency resulting from defects in acquisition or distribution of the metal causes anemia; whereas iron surfeit resulting from excessive iron absorption or defective utilization causes abnormal tissue iron deposition, leading to oxidative damage. Mammals utilize distinct mechanisms to regulate iron homeostasis at the systemic and cellular levels. These involve the hormone hepcidin and iron regulatory proteins, which collectively ensure iron balance. This review outlines recent advances in iron regulatory pathways, as well as in mechanisms underlying intracellular iron trafficking, an important but less-studied area of mammalian iron homeostasis. PMID:22703180

  9. Olfactory sensitivity in mammalian species.

    PubMed

    Wackermannová, M; Pinc, L; Jebavý, L

    2016-07-18

    Olfaction enables most mammalian species to detect and discriminate vast numbers of chemical structures called odorants and pheromones. The perception of such chemical compounds is mediated via two major olfactory systems, the main olfactory system and the vomeronasal system, as well as minor systems, such as the septal organ and the Grueneberg ganglion. Distinct differences exist not only among species but also among individuals in terms of their olfactory sensitivity; however, little is known about the mechanisms that determine these differences. In research on the olfactory sensitivity of mammals, scientists thus depend in most cases on behavioral testing. In this article, we reviewed scientific studies performed on various mammalian species using different methodologies and target chemical substances. Human and non-human primates as well as rodents and dogs are the most frequently studied species. Olfactory threshold studies on other species do not exist with the exception of domestic pigs. Olfactory testing performed on seals, elephants, and bats focused more on discriminative abilities than on sensitivity. An overview of olfactory sensitivity studies as well as olfactory detection ability in most studied mammalian species is presented here, focusing on comparable olfactory detection thresholds. The basics of olfactory perception and olfactory sensitivity factors are also described. PMID:27070753

  10. Sensory Feedback Control of Mammalian Vocalizations

    PubMed Central

    Smotherman, Michael S.

    2007-01-01

    Somatosensory and auditory feedback mechanisms are dynamic components of the vocal motor pattern generator in mammals. This review explores how sensory cues arising from central auditory and somatosensory pathways actively guide the production of both simple sounds and complex phrases in mammals. While human speech is a uniquely sophisticated example of mammalian vocal behavior, other mammals can serve as examples of how sensory feedback guides complex vocal patterns. Echolocating bats in particular are unique in their absolute dependence on voice control for survival: these animals must constantly adjust the acoustic and temporal patterns of their orientation sounds to efficiently navigate and forage for insects at high speeds under the cover of darkness. Many species of bats also utter a broad repertoire of communication sounds. The functional neuroanatomy of the bat vocal motor pathway is basically identical to other mammals, but the acute significance of sensory feedback in echolocation has made this a profitable model system for studying general principles of sensorimotor integration with regard to vocalizing. Bats and humans are similar in that they both maintain precise control of many different voice parameters, both exhibit a similar suite of responses to altered auditory feedback, and for both the efficacy of sensory feedback depends upon behavioral context. By comparing similarities and differences in the ways sensory feedback influences voice in humans and bats, we may shed light on the basic architecture of the mammalian vocal motor system and perhaps be able to better distinguish those features of human vocal control that evolved uniquely in support of speech and language. PMID:17449116

  11. Sensory feedback control of mammalian vocalizations.

    PubMed

    Smotherman, Michael S

    2007-09-01

    Somatosensory and auditory feedback mechanisms are dynamic components of the vocal motor pattern generator in mammals. This review explores how sensory cues arising from central auditory and somatosensory pathways actively guide the production of both simple sounds and complex phrases in mammals. While human speech is a uniquely sophisticated example of mammalian vocal behavior, other mammals can serve as examples of how sensory feedback guides complex vocal patterns. Echolocating bats in particular are unique in their absolute dependence on voice control for survival: these animals must constantly adjust the acoustic and temporal patterns of their orientation sounds to efficiently navigate and forage for insects at high speeds under the cover of darkness. Many species of bats also utter a broad repertoire of communication sounds. The functional neuroanatomy of the bat vocal motor pathway is basically identical to other mammals, but the acute significance of sensory feedback in echolocation has made this a profitable model system for studying general principles of sensorimotor integration with regard to vocalizing. Bats and humans are similar in that they both maintain precise control of many different voice parameters, both exhibit a similar suite of responses to altered auditory feedback, and for both the efficacy of sensory feedback depends upon behavioral context. By comparing similarities and differences in the ways sensory feedback influences voice in humans and bats, we may shed light on the basic architecture of the mammalian vocal motor system and perhaps be able to better distinguish those features of human vocal control that evolved uniquely in support of speech and language. PMID:17449116

  12. Adult Education in Greece

    ERIC Educational Resources Information Center

    Kokkos, Alexios

    2008-01-01

    The central aim of this article is to analyse the current situation of adult education in Greece. The article focuses on the following points: (a) the degree of participation in programmes of continuing professional training and general adult education courses, (b) the quality and the outcomes of the adult education provision in Greece, and (c)…

  13. Quantitative evaluation of mammalian skeletal muscle as a heterologous protein expression system.

    PubMed

    DiFranco, Marino; Neco, Patricia; Capote, Joana; Meera, Pratap; Vergara, Julio L

    2006-05-01

    The production of mammalian proteins in sufficient quantity and quality for structural and functional studies is a major challenge in biology. Intrinsic limitations of yeast and bacterial expression systems preclude their use for the synthesis of a significant number of mammalian proteins. This creates the necessity of well-identified expression systems based on mammalian cells. In this paper, we demonstrate that adult mammalian skeletal muscle, transfected in vivo by electroporation with DNA plasmids, is an excellent heterologous mammalian protein expression system. By using the fluorescent protein EGFP as a model, it is shown that muscle fibers express, during the course of a few days, large amounts of authentic replicas of transgenic proteins. Yields of approximately 1mg/g of tissue were obtained, comparable to those of other expression systems. The involvement of adult mammalian cells assures an optimal environment for proper protein folding and processing. All these advantages complement a methodology that is universally accessible to biomedical investigators and simple to implement. PMID:16325422

  14. Adult Neurogenesis: An Evolutionary Perspective.

    PubMed

    Kempermann, Gerd

    2016-02-01

    When adult neurogenesis was discovered in the mammalian brain it was often considered an atavism and, even today, many people are convinced that there has been a "phylogenetic reduction" away from lifelong neurogenesis, favoring stability for complex brains. Adult neurogenesis is found throughout the animal kingdom but varies to a large extent. Mammals might have fewer neurogenic zones than, for example, fish, but within their remaining neurogenic zones, the new neurons are highly functional. Especially, humans have very substantial quantities of neurogenesis in their hippocampus. At least for the mammalian dentate gyrus, one can thus argue that there has been evolution toward neurogenesis-based plasticity rather than away from it. PMID:26684183

  15. Social epidemiology of excess weight and central adiposity in older Indians: analysis of Study on global AGEing and adult health (SAGE)

    PubMed Central

    Samal, Sudipta; Panigrahi, Pinaki; Dutta, Ambarish

    2015-01-01

    Objectives We aimed to estimate the prevalence of overweight and obesity, represented by extra body weight and abdominal circumference, among older Indians; and to characterise the social pattern of obesity and measure the magnitude of hypertension attributable to it. Setting A nationally representative sample of older Indians was selected from 6 Indian states, including Rajasthan, Uttar Pradesh, West Bengal, Assam, Maharashtra and Karnataka, as a part of the multicountry Study on global AGEing and adult health (SAGE). Participants Indians aged 50 years or more (n=7273) were included in the first wave of the SAGE (2010), which we used in our study. Primary and secondary outcome measures The primary outcome measures included excess weight (EW), defined by body mass index (BMI) >25 kg/m2, and central adiposity (CA), defined by waist circumference >90 cm for men and >80 cm for women. The secondary outcome included hypertension, defined by systolic blood pressure >139 or diastolic blood pressure >79 mm Hg, or by those receiving antihypertensive medications. Results 14% of older Indians possessed EW, whereas 35% possessed CA; 50.9% of the wealthier third and 27.7% of the poorer two-thirds have CA; the proportions being 69.1% and 46.2%, respectively, in older women. Mostly wealth (adjusted OR for CA: 4.36 (3.23 to 5.95) and EW: 4.39 (3.49 to 5.53)), but also urban residence, privileged caste, higher education, white-collared occupation and female gender, were important determinants. One of 17 older Indians overall and 1 of 18 in the poorer 70% suffered from CA-driven hypertension, independent of BMI. Conclusions The problem of CA and its allied diseases is already substantial and expected to rise across all socioeconomic strata of older Indians, though currently, CA affects the privileged more than the underprivileged, in later life. Population-based promotion of appropriate lifestyles, with special emphasis on women, is required to counteract prosperity

  16. How difficult is inference of mammalian causal gene regulatory networks?

    PubMed

    Djordjevic, Djordje; Yang, Andrian; Zadoorian, Armella; Rungrugeecharoen, Kevin; Ho, Joshua W K

    2014-01-01

    Gene regulatory networks (GRNs) play a central role in systems biology, especially in the study of mammalian organ development. One key question remains largely unanswered: Is it possible to infer mammalian causal GRNs using observable gene co-expression patterns alone? We assembled two mouse GRN datasets (embryonic tooth and heart) and matching microarray gene expression profiles to systematically investigate the difficulties of mammalian causal GRN inference. The GRNs were assembled based on > 2,000 pieces of experimental genetic perturbation evidence from manually reading > 150 primary research articles. Each piece of perturbation evidence records the qualitative change of the expression of one gene following knock-down or over-expression of another gene. Our data have thorough annotation of tissue types and embryonic stages, as well as the type of regulation (activation, inhibition and no effect), which uniquely allows us to estimate both sensitivity and specificity of the inference of tissue specific causal GRN edges. Using these unprecedented datasets, we found that gene co-expression does not reliably distinguish true positive from false positive interactions, making inference of GRN in mammalian development very difficult. Nonetheless, if we have expression profiling data from genetic or molecular perturbation experiments, such as gene knock-out or signalling stimulation, it is possible to use the set of differentially expressed genes to recover causal regulatory relationships with good sensitivity and specificity. Our result supports the importance of using perturbation experimental data in causal network reconstruction. Furthermore, we showed that causal gene regulatory relationship can be highly cell type or developmental stage specific, suggesting the importance of employing expression profiles from homogeneous cell populations. This study provides essential datasets and empirical evidence to guide the development of new GRN inference methods for

  17. Evolutionary paths to mammalian cochleae.

    PubMed

    Manley, Geoffrey A

    2012-12-01

    Evolution of the cochlea and high-frequency hearing (>20 kHz; ultrasonic to humans) in mammals has been a subject of research for many years. Recent advances in paleontological techniques, especially the use of micro-CT scans, now provide important new insights that are here reviewed. True mammals arose more than 200 million years (Ma) ago. Of these, three lineages survived into recent geological times. These animals uniquely developed three middle ear ossicles, but these ossicles were not initially freely suspended as in modern mammals. The earliest mammalian cochleae were only about 2 mm long and contained a lagena macula. In the multituberculate and monotreme mammalian lineages, the cochlea remained relatively short and did not coil, even in modern representatives. In the lineage leading to modern therians (placental and marsupial mammals), cochlear coiling did develop, but only after a period of at least 60 Ma. Even Late Jurassic mammals show only a 270 ° cochlear coil and a cochlear canal length of merely 3 mm. Comparisons of modern organisms, mammalian ancestors, and the state of the middle ear strongly suggest that high-frequency hearing (>20 kHz) was not realized until the early Cretaceous (~125 Ma). At that time, therian mammals arose and possessed a fully coiled cochlea. The evolution of modern features of the middle ear and cochlea in the many later lineages of therians was, however, a mosaic and different features arose at different times. In parallel with cochlear structural evolution, prestins in therian mammals evolved into effective components of a new motor system. Ultrasonic hearing developed quite late-the earliest bat cochleae (~60 Ma) did not show features characteristic of those of modern bats that are sensitive to high ultrasonic frequencies. PMID:22983571

  18. Evaluation of the repeated-dose liver and gastrointestinal tract micronucleus assays with 22 chemicals using young adult rats: summary of the collaborative study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/The Japanese Environmental Mutagen Society (JEMS) - Mammalian Mutagenicity Study Group (MMS).

    PubMed

    Hamada, Shuichi; Ohyama, Wakako; Takashima, Rie; Shimada, Keisuke; Matsumoto, Kazumi; Kawakami, Satoru; Uno, Fuyumi; Sui, Hajime; Shimada, Yasushi; Imamura, Tadashi; Matsumura, Shoji; Sanada, Hisakazu; Inoue, Kenji; Muto, Shigeharu; Ogawa, Izumi; Hayashi, Aya; Takayanagi, Tomomi; Ogiwara, Yosuke; Maeda, Akihisa; Okada, Emiko; Terashima, Yukari; Takasawa, Hironao; Narumi, Kazunori; Wako, Yumi; Kawasako, Kazufumi; Sano, Masaki; Ohashi, Nobuyuki; Morita, Takeshi; Kojima, Hajime; Honma, Masamitsu; Hayashi, Makoto

    2015-03-01

    The repeated-dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect hepatocarcinogens. We conducted a collaborative study to assess the performance of this assay and to evaluate the possibility of integrating it into general toxicological studies. Twenty-four testing laboratories belonging to the Mammalian Mutagenicity Study Group, a subgroup of the Japanese Environmental Mutagen Society, participated in this trial. Twenty-two model chemicals, including some hepatocarcinogens, were tested in 14- and/or 28-day RDLMN assays. As a result, 14 out of the 16 hepatocarcinogens were positive, including 9 genotoxic hepatocarcinogens, which were reported negative in the bone marrow/peripheral blood micronucleus (MN) assay by a single treatment. These outcomes show the high sensitivity of the RDLMN assay to hepatocarcinogens. Regarding the specificity, 4 out of the 6 non-liver targeted genotoxic carcinogens gave negative responses. This shows the high organ specificity of the RDLMN assay. In addition to the RDLMN assay, we simultaneously conducted gastrointestinal tract MN assays using 6 of the above carcinogens as an optional trial of the collaborative study. The MN assay using the glandular stomach, which is the first contact site of the test chemical when administered by oral gavage, was able to detect chromosomal aberrations with 3 test chemicals including a stomach-targeted carcinogen. The treatment regime was the 14- and/or 28-day repeated-dose, and the regime is sufficiently promising to incorporate these methods into repeated-dose toxicological studies. The outcomes of our collaborative study indicated that the new techniques to detect chromosomal aberrations in vivo in several tissues worked successfully. PMID:25892619

  19. Mast cells in mammalian brain.

    PubMed

    Dropp, J J

    1976-01-01

    Mast cells, which had until recently been believed to be not present in the mammalian brain, were studied in the brains of 29 mammalian species. Although there was considerable intraspecific and interspecific variation, mast cells were most numerous within the leptomeninges (especially in those overlying the cerebrum and the dorsal thalamus - most rodents, most carnivores, chimpanzees, squirrel monkeys and elephant), the cerebral cortex (most rodents, tiger, fox, chimpanzee, tarsier, and elephant) and in many nuclei of the dorsal thalamus (most rodents, tiger, lion, and fox). In some mammals, mast cells were also numerous in the stroma of the telencephalic choroid plexuses (chimpanzee, squirrel monkey), the putamen and the claustrum (chimpanzee), the subfornical organ (pack rat, tiger, chimpanzee), the olfactory peduncles (hooded rat, albino rat), the stroma of the diencephalic choroid plexus (lion, chimpanzee, squirrel monkey), the pineal organ (chimpanzee, squirrel monkey), some nuclei of the hypothalamus (tiger), the infundibulum (hooded rat, tiger, fox) the area postrema (pack rat, chinchilla, lion, spider monkey, chimpanzee, fox) and some nuclei and tracts of the metencephalon and the myelencephalon (tiger). Neither the sex of the animal nor electrolytic lesions made in the brains of some of the animals at various times prior to sacrifice appeared to effect the number and the distribution of mast cells. Age-related changes in mast cell number and distribution were detected in the albino rat. PMID:961335

  20. DNA modifications in the mammalian brain

    PubMed Central

    Shin, Jaehoon; Ming, Guo-li; Song, Hongjun

    2014-01-01

    DNA methylation is a crucial epigenetic mark in mammalian development, genomic imprinting, X-inactivation, chromosomal stability and suppressing parasitic DNA elements. DNA methylation in neurons has also been suggested to play important roles for mammalian neuronal functions, and learning and memory. In this review, we first summarize recent discoveries and fundamental principles of DNA modifications in the general epigenetics field. We then describe the profiles of different DNA modifications in the mammalian brain genome. Finally, we discuss roles of DNA modifications in mammalian brain development and function. PMID:25135973

  1. Ion channels, phosphorylation and mammalian sperm capacitation

    PubMed Central

    Visconti, Pablo E; Krapf, Dario; de la Vega-Beltrán, José Luis; Acevedo, Juan José; Darszon, Alberto

    2011-01-01

    Sexually reproducing animals require an orchestrated communication between spermatozoa and the egg to generate a new individual. Capacitation, a maturational complex phenomenon that occurs in the female reproductive tract, renders spermatozoa capable of binding and fusing with the oocyte, and it is a requirement for mammalian fertilization. Capacitation encompasses plasma membrane reorganization, ion permeability regulation, cholesterol loss and changes in the phosphorylation state of many proteins. Novel tools to study sperm ion channels, image intracellular ionic changes and proteins with better spatial and temporal resolution, are unraveling how modifications in sperm ion transport and phosphorylation states lead to capacitation. Recent evidence indicates that two parallel pathways regulate phosphorylation events leading to capacitation, one of them requiring activation of protein kinase A and the second one involving inactivation of ser/thr phosphatases. This review examines the involvement of ion transporters and phosphorylation signaling processes needed for spermatozoa to achieve capacitation. Understanding the molecular mechanisms leading to fertilization is central for societies to deal with rising male infertility rates, to develop safe male gamete-based contraceptives and to preserve biodiversity through better assisted fertilization strategies. PMID:21540868

  2. Genome exposure and regulation in mammalian cells.

    PubMed

    Puck, T T; Webb, P; Johnson, R

    1998-09-01

    A method of measurement of exposed DNA (i.e. hypersensitive to DNase I hydrolysis) as opposed to sequestered (hydrolysis resistant) DNA in isolated nuclei of mammalian cells is described. While cell cultures exhibit some differences in behavior from day to day, the general pattern of exposed and sequestered DNA is satisfactorily reproducible and agrees with results previously obtained by other methods. The general pattern of DNA hydrolysis exhibited by all cells tested consists of a curve which at first rises sharply with increasing DNase I, and then becomes almost horizontal, indicating that roughly about half of the nuclear DNA is highly sequestered. In 4 cases where transformed cells (Raszip6, CHO, HL60 and PC12) were compared, each with its more normal homolog (3T3, and the reverse transformed versions of CHO, HL60 and PC12, achieved by dibutyryl cyclic AMP [DBcAMP], retinoic acid, and nerve growth factor [NGF] respectively), the transformed form displayed less genome exposure than the nontransformed form at every DNase I dose tested. When Ca++ was excluded from the hydrolysis medium in both the Raszip6-3T3 and the CHO-DBcAMP systems, the normal cell forms lost their increased exposure reverting to that of the transformed forms. Therefore Ca++ appears necessary for maintenance of the DNA in the more highly exposed state characteristic of the nontransformed phenotype. LiCl increases the DNA exposure of all transformed cells tested. Dextran sulfate and heparin each can increase the DNA exposure of several different cancers. Colcemid prevents the increase of exposure of CHO by DBcAMP but it must be administered before or simultaneously with the latter compound. Measurements on mouse biopsies reveal large differences in exposure in different normal tissues. Thus, the exposure from adult liver cells was greater than that of adult brain, but both fetal liver and fetal brain had significantly greater exposure than their adult counterparts. Exposure in normal human

  3. Efficacy and Safety of Mammalian Target of Rapamycin Inhibitors in Vascular Anomalies: A Systematic Review.

    PubMed

    Nadal, Marion; Giraudeau, Bruno; Tavernier, Elsa; Jonville-Bera, Annie-Pierre; Lorette, Gerárd; Maruani, Annabel

    2016-05-01

    Mammalian target of rapamycin (mTOR) inhibitors are a promising new treatment in vascular anomalies, but no published randomized controlled trials are available. The aim of this systematic review of all reported cases was to assess the efficacy and safety of mTOR inhibitors in all vascular anomalies, except cancers, in children and adults. In November 2014 MEDLINE, CENTRAL, LILACS and EMBASE were searched for studies of mTOR inhibitors in any vascular condition, except for malignant lesions, in humans. Fourteen publications and 9 posters, with data on 25 and 59 patients, respectively, all < 18 years old were included. Of these patients, 35.7% (n = 30) had vascular tumours, and 64.3% (n = 54) had malformations. Sirolimus was the most frequent mTOR inhibitor used (98.8%, n = 83). It was efficient in all cases, at a median time of 2 weeks (95% confidence interval 1-10 weeks). Sirolimus was well tolerated, the main side-effect being mouth sores, which led to treatment withdrawal in one case. The dosage of sirolimus was heterogeneous, the most common being 1.6 mg/m2/day. PMID:26607948

  4. Functional Zonation of the Adult Mammalian Adrenal Cortex

    PubMed Central

    Vinson, Gavin P.

    2016-01-01

    The standard model of adrenocortical zonation holds that the three main zones, glomerulosa, fasciculata, and reticularis each have a distinct function, producing mineralocorticoids (in fact just aldosterone), glucocorticoids, and androgens respectively. Moreover, each zone has its specific mechanism of regulation, though ACTH has actions throughout. Finally, the cells of the cortex originate from a stem cell population in the outer cortex or capsule, and migrate centripetally, changing their phenotype as they progress through the zones. Recent progress in understanding the development of the gland and the distribution of steroidogenic enzymes, trophic hormone receptors, and other factors suggests that this model needs refinement. Firstly, proliferation can take place throughout the gland, and although the stem cells are certainly located in the periphery, zonal replenishment can take place within zones. Perhaps more importantly, neither the distribution of enzymes nor receptors suggest that the individual zones are necessarily autonomous in their production of steroid. This is particularly true of the glomerulosa, which does not seem to have the full suite of enzymes required for aldosterone biosynthesis. Nor, in the rat anyway, does it express MC2R to account for the response of aldosterone to ACTH. It is known that in development, recruitment of stem cells is stimulated by signals from within the glomerulosa. Furthermore, throughout the cortex local regulatory factors, including cytokines, catecholamines and the tissue renin-angiotensin system, modify and refine the effects of the systemic trophic factors. In these and other ways it more and more appears that the functions of the gland should be viewed as an integrated whole, greater than the sum of its component parts. PMID:27378832

  5. Constitutive properties of adult mammalian cardiac muscle cells

    NASA Technical Reports Server (NTRS)

    Zile, M. R.; Richardson, K.; Cowles, M. K.; Buckley, J. M.; Koide, M.; Cowles, B. A.; Gharpuray, V.; Cooper, G. 4th

    1998-01-01

    BACKGROUND: The purpose of this study was to determine whether changes in the constitutive properties of the cardiac muscle cell play a causative role in the development of diastolic dysfunction. METHODS AND RESULTS: Cardiocytes from normal and pressure-hypertrophied cats were embedded in an agarose gel, placed on a stretching device, and subjected to a change in stress (sigma), and resultant changes in cell strain (epsilon) were measured. These measurements were used to examine the passive elastic spring, viscous damping, and myofilament activation. The passive elastic spring was assessed in protocol A by increasing the sigma on the agarose gel at a constant rate to define the cardiocyte sigma-versus-epsilon relationship. Viscous damping was assessed in protocol B from the loop area between the cardiocyte sigma-versus-epsilon relationship during an increase and then a decrease in sigma. In both protocols, myofilament activation was minimized by a reduction in [Ca2+]i. Myofilament activation effects were assessed in protocol C by defining cardiocyte sigma versus epsilon during an increase in sigma with physiological [Ca2+]i. In protocol A, the cardiocyte sigma-versus-epsilon relationship was similar in normal and hypertrophied cells. In protocol B, the loop area was greater in hypertrophied than normal cardiocytes. In protocol C, the sigma-versus-epsilon relation in hypertrophied cardiocytes was shifted to the left compared with normal cells. CONCLUSIONS: Changes in viscous damping and myofilament activation in combination may cause pressure-hypertrophied cardiocytes to resist changes in shape during diastole and contribute to diastolic dysfunction.

  6. Producing Newborn Synchronous Mammalian Cells

    NASA Technical Reports Server (NTRS)

    Gonda, Steve R.; Helmstetter, Charles E.; Thornton, Maureen

    2008-01-01

    A method and bioreactor for the continuous production of synchronous (same age) population of mammalian cells have been invented. The invention involves the attachment and growth of cells on an adhesive-coated porous membrane immersed in a perfused liquid culture medium in a microgravity analog bioreactor. When cells attach to the surface divide, newborn cells are released into the flowing culture medium. The released cells, consisting of a uniform population of synchronous cells are then collected from the effluent culture medium. This invention could be of interest to researchers investigating the effects of the geneotoxic effects of the space environment (microgravity, radiation, chemicals, gases) and to pharmaceutical and biotechnology companies involved in research on aging and cancer, and in new drug development and testing.

  7. Body Size in Mammalian Paleobiology

    NASA Astrophysics Data System (ADS)

    Damuth, John; MacFadden, Bruce J.

    1990-11-01

    This valuable collection of essays presents and evaluates techniques of body-mass estimation and reviews current and potential applications of body-size estimates in paleobiology. Papers discuss explicitly the errors and biases of various regression techniques and predictor variables, and the identification of functionally similar groups of species for improving the accuracy of estimates. At the same time other chapters review and discuss the physiological, ecological, and behavioral correlates of body size in extant mammals; the significance of body-mass distributions in mammalian faunas; and the ecology and evolution of body size in particular paleofaunas. Coverage is particularly detailed for carnivores, primates, and ungulates, but information is also presented on marsupials, rodents, and proboscideans.

  8. Determinants of Mammalian Nucleolar Architecture

    PubMed Central

    Farley, Katherine I.; Surovtseva, Yulia; Merkel, Janie; Baserga, Susan J.

    2015-01-01

    The nucleolus is responsible for the production of ribosomes, essential machines which synthesize all proteins needed by the cell. The structure of human nucleoli is highly dynamic and is directly related to its functions in ribosome biogenesis. Despite the importance of this organelle, the intricate relationship between nucleolar structure and function remains largely unexplored. How do cells control nucleolar formation and function? What are the minimal requirements for making a functional nucleolus? Here we review what is currently known regarding mammalian nucleolar formation at nucleolar organizer regions (NORs), which can be studied by observing the dissolution and reformation of the nucleolus during each cell division. Additionally, the nucleolus can be examined by analyzing how alterations in nucleolar function manifest in differences in nucleolar architecture. Furthermore, changes in nucleolar structure and function are correlated with cancer, highlighting the importance of studying the determinants of nucleolar formation. PMID:25670395

  9. Genetic Methods to Identify and Manipulate Newly Born Neurons in the Adult Brain

    PubMed Central

    Imayoshi, Itaru; Sakamoto, Masayuki; Kageyama, Ryoichiro

    2011-01-01

    Although mammalian neurogenesis is mostly completed by the perinatal period, new neurons are continuously generated in the subventricular zone of the lateral ventricle and the subgranular zone of the hippocampal dentate gyrus. Since the discovery of adult neurogenesis, many extensive studies have been performed on various aspects of adult neurogenesis, including proliferation and fate-specification of adult neural stem cells, and the migration, maturation and synaptic integration of newly born neurons. Furthermore, recent research has shed light on the intensive contribution of adult neurogenesis to olfactory-related and hippocampus-mediated brain functions. The field of adult neurogenesis progressed tremendously thanks to technical advances that facilitate the identification and selective manipulation of newly born neurons among billions of pre-existing neurons in the adult central nervous system. In this review, we introduce recent advances in the methodologies for visualizing newly generated neurons and manipulating neurogenesis in the adult brain. Particularly, the application of site-specific recombinases and Tet inducible system in combination with transgenic or gene targeting strategy is discussed in further detail. PMID:21562606

  10. Adult Neurogenesis in Fish.

    PubMed

    Ganz, Julia; Brand, Michael

    2016-01-01

    Teleost fish have a remarkable neurogenic and regenerative capacity in the adult throughout the rostrocaudal axis of the brain. The distribution of proliferation zones shows a remarkable conservation, even in distantly related teleost species, suggesting a common teleost ground plan of proliferation zones. There are different progenitor populations in the neurogenic niches-progenitors positive for radial glial markers (dorsal telencephalon, hypothalamus) and progenitors with neuroepithelial-like characteristics (ventral telencephalon, optic tectum, cerebellum). Definition of these progenitors has allowed studying their role in normal growth of the adult brain, but also when challenged following a lesion. From these studies, important roles have emerged for intrinsic mechanisms and extrinsic signals controlling the activation of adult neurogenesis that enable regeneration of the adult brain to occur, opening up new perspectives on rekindling regeneration also in the context of the mammalian brain. PMID:26747664

  11. Recent advances in mammalian protein production

    PubMed Central

    Bandaranayake, Ashok D.; Almo, Steven C.

    2014-01-01

    Mammalian protein production platforms have had a profound impact in many areas of basic and applied research, and an increasing number of blockbuster drugs are recombinant mammalian proteins. With global sales of these drugs exceeding US$120 billion per year, both industry and academic research groups continue to develop cost effective methods for producing mammalian proteins to support preclinical and clinical evaluations of potential therapeutics. While a wide range of platforms have been successfully exploited for laboratory use, the bulk of recent biologics have been produced in mammalian cell lines due to the requirement for post translational modification and the biosynthetic complexity of the target proteins. In this review we highlight the range of mammalian expression platforms available for recombinant protein production, as well as advances in technologies for the rapid and efficient selection of highly productive clones. PMID:24316512

  12. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    PubMed Central

    Costa, Liliana; Faustino, Maria Amparo F.; Neves, Maria Graça P. M. S.; Cunha, Ângela; Almeida, Adelaide

    2012-01-01

    Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process. PMID:22852040

  13. Redescription of the adults and new descriptions of the previously unknown immature stages of Culex (Culex) articularis Philippi, 1865 (Diptera: Culicidae) from central Chile.

    PubMed

    González, Christian R; Reyes, Carolina; Rada, Viviana

    2015-01-01

    Male and female adults of Culex (Culex) articularis Philippi are redescribed, and the 4th-instar larva and pupa are described and illustrated for the first time. Culex articularis is compared with other species of the subgenus Culex. Illustrations of diagnostic characters of the female, male genitalia, 4th-instar larva, and pupa are also provided. PMID:25947865

  14. Development of a Performance Assessment System for the Central New York External High School Diploma Program: An Educational Alternative for Adults: A Progress Report.

    ERIC Educational Resources Information Center

    Nickse, Ruth S.

    The report describes the development of an alternative performance assessment procedure for certifying adults at the secondary school level in the New York External High School Diploma Program. Unlike standardized group tests, the alternative method is characterized by such features as flexibility in time and location of testing, variety of…

  15. Mammalian reproduction: an ecological perspective.

    PubMed

    Bronson, F H

    1985-02-01

    The objectives of this paper are to organize our concepts about the environmental regulation of reproduction in mammals and to delineate important gaps in our knowledge of this subject. The environmental factors of major importance for mammalian reproduction are food availability, ambient temperature, rainfall, the day/night cycle and a variety of social cues. The synthesis offered here uses as its core the bioenergetic control of reproduction. Thus, for example, annual patterns of breeding are viewed as reflecting primarily the caloric costs of the female's reproductive effort as they relate to the energetic costs and gains associated with her foraging effort. Body size of the female is an important consideration since it is correlated with both potential fat reserves and life span. Variation in nutrient availability may or may not be an important consideration. The evolutionary forces that have shaped the breeding success of males usually are fundamentally different from those acting on females and, by implication, the environmental controls governing reproduction probably also often differ either qualitatively or quantitatively in the two sexes. Mammals often live in habitats where energetic and nutrient challenges vary seasonally, even in the tropics. When seasonal breeding is required, a mammal may use a predictor such as photoperiod or a secondary plant compound to prepare metabolically for reproduction. A reasonable argument can be made, however, that opportunistic breeding, unenforced by a predictor, may be the most prevalent strategy extant among today's mammals. Social cues can have potent modulating actions. They can act either via discrete neural and endocrine pathways to alter specific processes such as ovulation, or they can induce nonspecific emotional states that secondarily affect reproduction. Many major gaps remain in our knowledge about the environmental regulation of mammalian reproduction. For one, we have a paucity of information about the

  16. Central NPY-Y5 receptors activation plays a major role in fasting-induced pituitary-thyroid axis suppression in adult rat.

    PubMed

    Costa-e-Sousa, Ricardo Henrique; Souza, Luana Lopes; Calviño, Camila; Cabanelas, Adriana; Almeida, Norma Aparecida Santos; Oliveira, Karen Jesus; Pazos-Moura, Carmen Cabanelas

    2011-11-10

    Neuropeptide Y (NPY) inhibits TRH neurons in fed state, and hypothalamic NPY higher expression during fasting has been proposed to be involved in fasting-induced suppression of the hypothalamus-pituitary-thyroid (HPT) axis. We investigated the role of central Y5 receptors in the control of thyrotropin (TSH) and thyroid hormone (TH) secretion. Fed and fasting rats received twice daily central injections (3rd ventricle) of Y5 receptor antagonist (CGP71683; 15nmol/rat) for 72h. Fasted rats also received a single central injection of CGP71683 (15nmol/rat) at the end of 72h of fasting. In fed rats, Y5 receptor blockade reduced total food intake by 32% and body mass by almost 10% (p<0.01), corroborating the role of this receptor in food intake control. 72h-fasted rats exhibited a 4-fold increase in serum TSH (p<0.001), 1h after a single injection of Y5 antagonist. Also with multiple injections during 72h of fasting, Y5 blockade resulted in activation of thyroid axis, as demonstrated by a 3-times rise in serum T4 (p<0.001), accompanied by unchanged TSH and T3. In fed rats, the chronic central administration of CGP71683 resulted in reduced total serum T4 without changes in free T4 and TSH. Serum leptin and PYY were not altered by the NPY central blockade in both fed and fasted rats, suggesting no role of these hormones in the alterations observed. Therefore, the inhibition of central Y5 neurotransmission resulted in activation of thyroid axis during fasting suggesting that NPY-Y5 receptors contribute to fasting-induced TSH and TH suppression. PMID:21771616

  17. Perinatal taurine exposure affects adult arterial pressure control.

    PubMed

    Roysommuti, Sanya; Wyss, J Michael

    2014-01-01

    Taurine is an abundant, free amino acid found in mammalian cells that contributes to many physiologic functions from that of a simple cell osmolyte to a programmer of adult health and disease. Taurine's contribution extends from conception throughout life, but its most critical exposure period is during perinatal life. In adults, taurine supplementation prevents or alleviates cardiovascular disease and related complications. In contrast, low taurine consumption coincides with increased risk of cardiovascular disease, obesity and type II diabetes. This review focuses on the effects that altered perinatal taurine exposure has on long-term mechanisms that control adult arterial blood pressure and could thereby contribute to arterial hypertension through its ability to program these cardiovascular regulatory mechanisms very early in life. The modifications of these mechanisms can last a lifetime and transfer to the next generation, suggesting that epigenetic mechanisms underlie the changes. The ability of perinatal taurine exposure to influence arterial pressure control mechanisms and hypertension in adult life appears to involve the regulation of growth and development, the central and autonomic nervous system, the renin-angiotensin system, glucose-insulin interaction and changes to heart, blood vessels and kidney function. PMID:23070226

  18. Authenticity in Adult Learning

    ERIC Educational Resources Information Center

    Ashton, Sam

    2010-01-01

    This paper is concerned with the relationship between authenticity and adult learning and prompted by some studies in which adult "authentic learning" is a central concept. The implication revealed by them is that real-worldness of learning contexts, learning content and learning tasks is perceived as conferring authenticity on learning. Here,…

  19. Possible mechanisms of mammalian immunocontraception.

    PubMed

    Barber, M R; Fayrer-Hosken, R A

    2000-03-01

    Ecological and conservation programs in ecosystems around the world have experienced varied success in population management. One of the greatest problems is that human expansion has led to the shrinking of wildlife habitat and, as a result, the overpopulation of many different species has occurred. The pressures exerted by the increased number of animals has caused environmental damage. The humane and practical control of these populations has solicited the scientific community to arrive at a safe, effective, and cost-efficient means of population control. Immunocontraception using zona pellucida antigens, specifically porcine zona pellucida (pZP), has become one of the most promising population control tools in the world today, with notable successes in horses and elephants. A conundrum has risen where pZP, a single vaccine, successfully induces an immunocontraceptive effect in multiple species of mammals. This review describes the most current data pertaining to the mammalian zona pellucida and immunocontraception, and from these studies, we suggest several potential mechanisms of immunocontraception. PMID:10706942

  20. Mammalian cell cultivation in space

    NASA Astrophysics Data System (ADS)

    Gmünder, Felix K.; Suter, Robert N.; Kiess, M.; Urfer, R.; Nordau, C.-G.; Cogoli, A.

    Equipment used in space for the cultivation of mammalian cells does not meet the usual standard of earth bound bioreactors. Thus, the development of a space worthy bioreactor is mandatory for two reasons: First, to investigate the effect on single cells of the space environment in general and microgravity conditions in particular, and second, to provide researchers on long term missions and the Space Station with cell material. However, expertise for this venture is not at hand. A small and simple device for animal cell culture experiments aboard Spacelab (Dynamic Cell Culture System; DCCS) was developed. It provides 2 cell culture chambers, one is operated as a batch system, the other one as a perfusion system. The cell chambers have a volume of 200 μl. Medium exchange is achieved with an automatic osmotic pump. The system is neither mechanically stirred nor equipped with sensors. Oxygen for cell growth is provided by a gas chamber that is adjacent to the cell chambers. The oxygen gradient produced by the growing cells serves to maintain the oxygen influx by diffusion. Hamster kidney cells growing on microcarriers were used to test the biological performance of the DCCS. On ground tests suggest that this system is feasible.

  1. Mammalian mitochondrial beta-oxidation.

    PubMed Central

    Eaton, S; Bartlett, K; Pourfarzam, M

    1996-01-01

    The enzymic stages of mammalian mitochondrial beta-oxidation were elucidated some 30-40 years ago. However, the discovery of a membrane-associated multifunctional enzyme of beta-oxidation, a membrane-associated acyl-CoA dehydrogenase and characterization of the carnitine palmitoyl transferase system at the protein and at the genetic level has demonstrated that the enzymes of the system itself are incompletely understood. Deficiencies of many of the enzymes have been recognized as important causes of disease. In addition, the study of these disorders has led to a greater understanding of the molecular mechanism of beta-oxidation and the import, processing and assembly of the beta-oxidation enzymes within the mitochondrion. The tissue-specific regulation, intramitochondrial control and supramolecular organization of the pathway is becoming better understood as sensitive analytical and molecular techniques are applied. This review aims to cover enzymological and organizational aspects of mitochondrial beta-oxidation together with the biochemical aspects of inherited disorders of beta-oxidation and the intrinsic control of beta-oxidation. PMID:8973539

  2. Cell death in mammalian development.

    PubMed

    Penaloza, C; Orlanski, S; Ye, Y; Entezari-Zaher, T; Javdan, M; Zakeri, Z

    2008-01-01

    During embryogenesis there is an exquisite orchestration of cellular division, movement, differentiation, and death. Cell death is one of the most important aspects of organization of the developing embryo, as alteration in timing, level, or pattern of cell death can lead to developmental anomalies. Cell death shapes the embryo and defines the eventual functions of the organs. Cells die using different paths; understanding which path a dying cell takes helps us define the signals that regulate the fate of the cell. Our understanding of cell death in development stems from a number of observations indicating genetic regulation of the death process. With today's increased knowledge of the pathways of cell death and the identification of the genes whose products regulate the pathways we know that, although elimination of some of these gene products has no developmental phenotype, alteration of several others has profound effects. In this review we discuss the types and distributions of cell death seen in developing mammalian embryos as well as the gene products that may regulate the process. PMID:18220829

  3. Ghrelin Receptors in Non-Mammalian Vertebrates

    PubMed Central

    Kaiya, Hiroyuki; Kangawa, Kenji; Miyazato, Mikiya

    2012-01-01

    The growth hormone secretagogue-receptor (GHS-R) was discovered in humans and pigs in 1996. The endogenous ligand, ghrelin, was discovered 3 years later, in 1999, and our understanding of the physiological significance of the ghrelin system in vertebrates has grown steadily since then. Although the ghrelin system in non-mammalian vertebrates is a subject of great interest, protein sequence data for the receptor in non-mammalian vertebrates has been limited until recently, and related biological information has not been well organized. In this review, we summarize current information related to the ghrelin receptor in non-mammalian vertebrates. PMID:23882259

  4. Monoclonal antibodies to a rat nestin fusion protein recognize a 220-kDa polypeptide in subsets of fetal and adult human central nervous system neurons and in primitive neuroectodermal tumor cells.

    PubMed Central

    Tohyama, T.; Lee, V. M.; Rorke, L. B.; Marvin, M.; McKay, R. D.; Trojanowski, J. Q.

    1993-01-01

    Nestin is the major intermediate filament protein of embryonic central nervous system (CNS) progenitor cells. To identify proteins involved in early stages of lineage commitment in the developing human CNS we generated monoclonal antibodies to a TrpE-rat nestin fusion protein. This resulted in a monoclonal antibody (designated NST11) that did not recognize authentic human nestin, but did recognize a novel neuron-specific human polypeptide expressed in a subset of embryonic and adult CNS neurons as well as in medulloblastomas. NST11 immunoreactivity was abundant in developing spinal cord motor neurons, but was extinguished in these neurons by 17 weeks gestation. NST11 also labeled Purkinje cells at 17 weeks gestation, but Purkinje cells continued to express the NST11 antigen throughout gestation as well as in the adult cerebellum, and NST11 immunoreactivity was more abundant in Purkinje cells than in any other human CNS neurons. No NST11 immunoreactivity was detected in cells of the adult human peripheral nervous system or in a variety of adult non-neural human tissues. Further, NST11 almost exclusively stained cerebellar medulloblastomas. In Western blots of immature and mature human cerebral and cerebellar extracts, NST11 did not bind human nestin, but did detect an immunoband with a molecular weight of 220 kd. A similar immunoband was detected in medulloblastoma-derived cell lines with a neuron-like phenotype. These findings suggest that the NST11 monoclonal antibody recognizes a novel protein expressed by a subpopulation of immature and mature human CNS neurons, medulloblastomas, and medulloblastoma-derived cell lines. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7686344

  5. Computational models of adult neurogenesis

    NASA Astrophysics Data System (ADS)

    Cecchi, Guillermo A.; Magnasco, Marcelo O.

    2005-10-01

    Experimental results in recent years have shown that adult neurogenesis is a significant phenomenon in the mammalian brain. Little is known, however, about the functional role played by the generation and destruction of neurons in the context of an adult brain. Here, we propose two models where new projection neurons are incorporated. We show that in both models, using incorporation and removal of neurons as a computational tool, it is possible to achieve a higher computational efficiency that in purely static, synapse-learning-driven networks. We also discuss the implication for understanding the role of adult neurogenesis in specific brain areas like the olfactory bulb and the dentate gyrus.

  6. All-Trans Retinoic Acid Induces Expression of a Novel Intergenic Long Noncoding RNA in Adult rat Primary Hippocampal Neurons.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2016-02-01

    Around 90% of the mammalian genome undergoes pervasive transcription into various types of small and long regulatory noncoding RNAs, whereas only ∼ 1.5% codes for proteins. Long noncoding RNAs (lncRNAs) constitute diverse classes of sense- and antisense transcripts that are abundantly expressed in the mammalian central nervous system (CNS) in cell type- and developmental stage-specific manners. They are implicated in brain development, differentiation, neuronal plasticity, and other cognitive functions. Mammalian brain requires the vitamin A metabolite all-trans retinoic acid (atRA) for its normal development, differentiation, and cell-fate determination. However, its role in adult brain function is less understood. Here, we report atRA-mediated transcriptional upregulation of endogenous expression of a novel long intergenic noncoding RNA-rat brain expressed (LINC-RBE) in cultured primary hippocampal neurons from adult rat. We have previously reported LINC-RBE as an intergenic, simple repeat sequence containing lncRNA highly expressed in the rat brain. This is a first-time report of involvement of atRA in transcriptional upregulation of lncRNA expression in rat hippocampal neurons. Therefore, it may be involved in regulation of brain function and disease. PMID:26572536

  7. Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes.

    PubMed

    Zebrowski, David C; Vergarajauregui, Silvia; Wu, Chi-Chung; Piatkowski, Tanja; Becker, Robert; Leone, Marina; Hirth, Sofia; Ricciardi, Filomena; Falk, Nathalie; Giessl, Andreas; Just, Steffen; Braun, Thomas; Weidinger, Gilbert; Engel, Felix B

    2015-01-01

    Mammalian cardiomyocytes become post-mitotic shortly after birth. Understanding how this occurs is highly relevant to cardiac regenerative therapy. Yet, how cardiomyocytes achieve and maintain a post-mitotic state is unknown. Here, we show that cardiomyocyte centrosome integrity is lost shortly after birth. This is coupled with relocalization of various centrosome proteins to the nuclear envelope. Consequently, postnatal cardiomyocytes are unable to undergo ciliogenesis and the nuclear envelope adopts the function as cellular microtubule organizing center. Loss of centrosome integrity is associated with, and can promote, cardiomyocyte G0/G1 cell cycle arrest suggesting that centrosome disassembly is developmentally utilized to achieve the post-mitotic state in mammalian cardiomyocytes. Adult cardiomyocytes of zebrafish and newt, which are able to proliferate, maintain centrosome integrity. Collectively, our data provide a novel mechanism underlying the post-mitotic state of mammalian cardiomyocytes as well as a potential explanation for why zebrafish and newts, but not mammals, can regenerate their heart. PMID:26247711

  8. Enhancer Evolution across 20 Mammalian Species

    PubMed Central

    Villar, Diego; Berthelot, Camille; Aldridge, Sarah; Rayner, Tim F.; Lukk, Margus; Pignatelli, Miguel; Park, Thomas J.; Deaville, Robert; Erichsen, Jonathan T.; Jasinska, Anna J.; Turner, James M.A.; Bertelsen, Mads F.; Murchison, Elizabeth P.; Flicek, Paul; Odom, Duncan T.

    2015-01-01

    Summary The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammalian regulatory evolution. PMID:25635462

  9. Mammalian synthetic biology: emerging medical applications

    PubMed Central

    Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M.; Krams, Rob

    2015-01-01

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON–OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. PMID:25808341

  10. Mammalian Response to Cenozoic Climatic Change

    NASA Astrophysics Data System (ADS)

    Blois, Jessica L.; Hadly, Elizabeth A.

    2009-05-01

    Multiple episodes of rapid and gradual climatic changes influenced the evolution and ecology of mammalian species and communities throughout the Cenozoic. Climatic change influenced the abundance, genetic diversity, morphology, and geographic ranges of individual species. Within communities these responses interacted to catalyze immigration, speciation, and extinction. Combined they affected long-term patterns of community stability, functional turnover, biotic turnover, and diversity. Although the relative influence of climate on particular evolutionary processes is oft debated, an understanding of processes at the root of biotic change yields important insights into the complexity of mammalian response. Ultimately, all responses trace to events experienced by populations. However, many such processes emerge as patterns above the species level, where shared life history traits and evolutionary history allow us to generalize about mammalian response to climatic change. These generalizations provide the greatest power to understand and predict mammalian responses to current and future global change.

  11. Bats and Rodents Shape Mammalian Retroviral Phylogeny

    PubMed Central

    Cui, Jie; Tachedjian, Gilda; Wang, Lin-Fa

    2015-01-01

    Endogenous retroviruses (ERVs) represent past retroviral infections and accordingly can provide an ideal framework to infer virus-host interaction over their evolutionary history. In this study, we target high quality Pol sequences from 7,994 Class I and 8,119 Class II ERVs from 69 mammalian genomes and surprisingly find that retroviruses harbored by bats and rodents combined occupy the major phylogenetic diversity of both classes. By analyzing transmission patterns of 30 well-defined ERV clades, we corroborate the previously published observation that rodents are more competent as originators of mammalian retroviruses and reveal that bats are more capable of receiving retroviruses from non-bat mammalian origins. The powerful retroviral hosting ability of bats is further supported by a detailed analysis revealing that the novel bat gammaretrovirus, Rhinolophus ferrumequinum retrovirus, likely originated from tree shrews. Taken together, this study advances our understanding of host-shaped mammalian retroviral evolution in general. PMID:26548564

  12. Bats and Rodents Shape Mammalian Retroviral Phylogeny.

    PubMed

    Cui, Jie; Tachedjian, Gilda; Wang, Lin-Fa

    2015-01-01

    Endogenous retroviruses (ERVs) represent past retroviral infections and accordingly can provide an ideal framework to infer virus-host interaction over their evolutionary history. In this study, we target high quality Pol sequences from 7,994 Class I and 8,119 Class II ERVs from 69 mammalian genomes and surprisingly find that retroviruses harbored by bats and rodents combined occupy the major phylogenetic diversity of both classes. By analyzing transmission patterns of 30 well-defined ERV clades, we corroborate the previously published observation that rodents are more competent as originators of mammalian retroviruses and reveal that bats are more capable of receiving retroviruses from non-bat mammalian origins. The powerful retroviral hosting ability of bats is further supported by a detailed analysis revealing that the novel bat gammaretrovirus, Rhinolophus ferrumequinum retrovirus, likely originated from tree shrews. Taken together, this study advances our understanding of host-shaped mammalian retroviral evolution in general. PMID:26548564

  13. Mammalian synthetic biology: emerging medical applications.

    PubMed

    Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M; Krams, Rob

    2015-05-01

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. PMID:25808341

  14. Reverse genetics for mammalian reovirus.

    PubMed

    Boehme, Karl W; Ikizler, Miné; Kobayashi, Takeshi; Dermody, Terence S

    2011-10-01

    Mammalian orthoreoviruses (reoviruses) are highly tractable models for studies of viral replication and pathogenesis. The versatility of reovirus as an experimental model has been enhanced by development of a plasmid-based reverse genetics system. Infectious reovirus can be recovered from cells transfected with plasmids encoding cDNAs of each reovirus gene segment using a strategy that does not require helper virus and is independent of selection. In this system, transcription of each gene segment is driven by bacteriophage T7 RNA polymerase, which can be supplied transiently by recombinant vaccinia virus (rDIs-T7pol) or by cells that constitutively express the enzyme. Reverse genetics systems have been developed for two prototype reovirus strains, type 1 Lang (T1L) and type 3 Dearing (T3D). Each reovirus cDNA was encoded on an independent plasmid for the first-generation rescue system. The efficiency of virus recovery was enhanced in a second-generation system by combining the cDNAs for multiple reovirus gene segments onto single plasmids to reduce the number of plasmids from 10 to 4. The reduction in plasmid number and the use of baby hamster kidney cells that express T7 RNA polymerase increased the efficiency of viral rescue, reduced the incubation time required to recover infectious virus, and eliminated potential biosafety concerns associated with the use of recombinant vaccinia virus. Reovirus reverse genetics has been used to introduce mutations into viral capsid and nonstructural components to study viral protein-structure activity relationships and can be exploited to engineer recombinant reoviruses for vaccine and oncolytic applications. PMID:21798351

  15. Hacking the genetic code of mammalian cells.

    PubMed

    Schwarzer, Dirk

    2009-07-01

    A genetic shuttle: The highlighted article, which was recently published by Schultz, Geierstanger and co-workers, describes a straightforward scheme for enlarging the genetic code of mammalian cells. An orthogonal tRNA/aminoacyl-tRNA synthetase pair specific for a new amino acid can be evolved in E. coli and subsequently transferred into mammalian cells. The feasibility of this approach was demonstrated by adding a photocaged lysine derivative to the genetic repertoire of a human cell line. PMID:19533721

  16. Simplified Bioreactor For Growing Mammalian Cells

    NASA Technical Reports Server (NTRS)

    Spaulding, Glenn F.

    1995-01-01

    Improved bioreactor for growing mammalian cell cultures developed. Designed to support growth of dense volumes of mammalian cells by providing ample, well-distributed flows of nutrient solution with minimal turbulence. Cells relatively delicate and, unlike bacteria, cannot withstand shear forces present in turbulent flows. Bioreactor vessel readily made in larger sizes to accommodate greater cell production quantities. Molding equipment presently used makes cylinders up to 30 centimeters long. Alternative sintered plastic techniques used to vary pore size and quantity, as necessary.

  17. How common is the lipid body-containing interstitial cell in the mammalian lung?

    PubMed

    Tahedl, Daniel; Wirkes, André; Tschanz, Stefan A; Ochs, Matthias; Mühlfeld, Christian

    2014-09-01

    Pulmonary lipofibroblasts are thought to be involved in lung development, regeneration, vitamin A storage, and surfactant synthesis. Most of the evidence for these important functions relies on mouse or rat studies. Therefore, the present study was designed to investigate the presence of lipofibroblasts in a variety of early postnatal and adult mammalian species (including humans) to evaluate the ability to generalize functions of this cell type for other species. For this purpose, lung samples from 14 adult mammalian species as well as from postnatal mice, rats, and humans were investigated using light and electron microscopic stereology to obtain the volume fraction and the total volume of lipid bodies. In adult animals, lipid bodies were observed only, but not in all rodents. In all other species, no lipofibroblasts were observed. In rodents, lipid body volume scaled with body mass with an exponent b = 0.73 in the power law equation. Lipid bodies were not observed in postnatal human lungs but showed a characteristic postnatal increase in mice and rats and persisted at a lower level in the adult animals. Among 14 mammalian species, lipofibroblasts were only observed in rodents. The great increase in lipid body volume during early postnatal development of the mouse lung confirms the special role of lipofibroblasts during rodent lung development. It is evident that the cellular functions of pulmonary lipofibroblasts cannot be transferred easily from rodents to other species, in particular humans. PMID:24973404

  18. Young aphids avoid erroneous dropping when evading mammalian herbivores by combining input from two sensory modalities.

    PubMed

    Gish, Moshe; Dafni, Amots; Inbar, Moshe

    2012-01-01

    Mammalian herbivores may incidentally ingest plant-dwelling insects while foraging. Adult pea aphids (Acyrthosiphon pisum) avoid this danger by dropping off their host plant after sensing the herbivore's warm and humid breath and the vibrations it causes while feeding. Aphid nymphs may also drop (to escape insect enemies), but because of their slow movement, have a lower chance of finding a new plant. We compared dropping rates of first-instar nymphs with those of adults, after exposing pea aphids to different combinations of simulated mammalian breath and vibrations. We hypothesized that nymphs would compensate for the greater risk they face on the ground by interpreting more conservatively the mammalian herbivore cues they perceive. Most adults dropped in response to breath alone, but nymphs rarely did so. Breath stimulus accompanied by one concurrent vibrational stimulus, caused a minor rise in adult dropping rates. Adding a second vibration during breath had no additional effect on adults. The nymphs, however, relied on a combination of the two types of stimuli, with a threefold increase in dropping rates when the breath was accompanied by one vibration, and a further doubling of dropping rates when the second vibration was added. The age-specificity of the aphids' herbivore detection mechanism is probably an adaptation to the different cost of dropping for the different age groups. Relying on a combination of stimuli from two sensory modalities enables the vulnerable nymphs to avoid costly mistakes. Our findings emphasize the importance of the direct trophic effect of mammalian herbivory for plant-dwelling insects. PMID:22496734

  19. Young Aphids Avoid Erroneous Dropping when Evading Mammalian Herbivores by Combining Input from Two Sensory Modalities

    PubMed Central

    Gish, Moshe; Dafni, Amots; Inbar, Moshe

    2012-01-01

    Mammalian herbivores may incidentally ingest plant-dwelling insects while foraging. Adult pea aphids (Acyrthosiphon pisum) avoid this danger by dropping off their host plant after sensing the herbivore's warm and humid breath and the vibrations it causes while feeding. Aphid nymphs may also drop (to escape insect enemies), but because of their slow movement, have a lower chance of finding a new plant. We compared dropping rates of first-instar nymphs with those of adults, after exposing pea aphids to different combinations of simulated mammalian breath and vibrations. We hypothesized that nymphs would compensate for the greater risk they face on the ground by interpreting more conservatively the mammalian herbivore cues they perceive. Most adults dropped in response to breath alone, but nymphs rarely did so. Breath stimulus accompanied by one concurrent vibrational stimulus, caused a minor rise in adult dropping rates. Adding a second vibration during breath had no additional effect on adults. The nymphs, however, relied on a combination of the two types of stimuli, with a threefold increase in dropping rates when the breath was accompanied by one vibration, and a further doubling of dropping rates when the second vibration was added. The age-specificity of the aphids' herbivore detection mechanism is probably an adaptation to the different cost of dropping for the different age groups. Relying on a combination of stimuli from two sensory modalities enables the vulnerable nymphs to avoid costly mistakes. Our findings emphasize the importance of the direct trophic effect of mammalian herbivory for plant-dwelling insects. PMID:22496734

  20. Prevalence of Diabetes and Intermediate Hyperglycemia Among Adults From the First Multinational Study of Noncommunicable Diseases in Six Central American Countries

    PubMed Central

    Barcelo, Alberto; Gregg, Edward W.; Gerzoff, Robert B.; Wong, Roy; Perez Flores, Enrique; Ramirez-Zea, Manuel; Cafiero, Elizabeth; Altamirano, Lesbia; Ascencio Rivera, Melanie; de Cosio, Gerardo; de Maza, Martha Dinorah; del Aguila, Roberto; Emanuel, Englebert; Gil, Enrique; Gough, Ethan; Jenkins, Valerie; Orellana, Patrícia; Palma, Ruben; Palomo, Ruben; Pastora, Martha; Peña, Rodolfo; Pineda, Elia; Rodriguez, Bismark; Tacsan, Luis; Thompson, Loraine; Villagra, Lucy

    2012-01-01

    OBJECTIVE The increasing burdens of obesity and diabetes are two of the most prominent threats to the health of populations of developed and developing countries alike. The Central America Diabetes Initiative (CAMDI) is the first study to examine the prevalence of diabetes in Central America. RESEARCH DESIGN AND METHODS The CAMDI survey was a cross-sectional survey based on a probabilistic sample of the noninstitutionalized population of five Central American populations conducted between 2003 and 2006. The total sample population was 10,822, of whom 7,234 (67%) underwent anthropometry measurement and a fasting blood glucose or 2-h oral glucose tolerance test. RESULTS The total prevalence of diabetes was 8.5%, but was higher in Belize (12.9%) and lower in Honduras (5.4%). Of the screened population, 18.6% had impaired glucose tolerance/impaired fasting glucose. CONCLUSIONS As this population ages, the prevalence of diabetes is likely to continue to rise in a dramatic and devastating manner. Preventive strategies must be quickly introduced. PMID:22323417

  1. Detection of human herpesvirus-6 in adult central nervous system tumors: predominance of early and late viral antigens in glial tumors.

    PubMed

    Crawford, John R; Santi, Maria Rita; Cornelison, Robbie; Sallinen, Satu-Leena; Haapasalo, Hannu; MacDonald, Tobey J

    2009-10-01

    The purpose is to determine the incidence of active and latent human herpesvirus-6 (HHV-6) infection in a large cohort of adult primary and recurrent CNS tumors. We screened a tissue microarray (TMA) containing more than 200 adult primary and recurrent CNS tumors with known clinical information for the presence of HHV-6 DNA by in situ hybridization (ISH) and protein by immunohistochemistry (IHC). One hundred six of 224 (47%) CNS tumors were positive for HHV-6 U57 Major Capsid Protein (MCP) gene by ISH compared to 0/25 non tumor control brain (P = 0.001). Fourteen of 30 (47%) tumors were HHV-6 MCP positive by nested PCR compared to 0/25 non-tumor brain controls (P = 0.001), revealing HHV-6 Variant A in 6 of 14 samples. HHV-6A/B early (p41) and late (gp116/64/54) antigens were detected by IHC in 66 of 277 (24%) (P = 0.003) and 84 of 282 (35%) (P = 0.002) tumors, respectively, suggesting active infection. HHV-6 p41 (P = 0.645) and gp116/64/54 (P = 0.198) antigen detection was independent of recurrent disease. Glial tumors were 3 times more positive by IHC compared to non glial tumors for both HHV-6 gp116/64/54 (P = 0.0002) and HHV-6 p41 (P = 0.004). Kaplan Meier survival analysis showed no effect of HHV-6 gp116/64/54 (P = 0.852) or HHV-6 p41 (P = 0.817) antigen detection on survival. HHV-6 early and late antigens are detected in adult primary and recurrent CNS tumors more frequently in glial tumors. We hypothesize that the glial-tropic features of HHV-6 may play an important modifying role in tumor biology that warrants further investigation. PMID:19424665

  2. Mammalian phylogeny reveals recent diversification rate shifts.

    PubMed

    Stadler, Tanja

    2011-04-12

    Phylogenetic trees of present-day species allow investigation of the rate of evolution that led to the present-day diversity. A recent analysis of the mammalian phylogeny challenged the view of explosive mammalian evolution after the Cretaceous-Tertiary (K/T) boundary (65 Mya). However, due to lack of appropriate methods, the diversification (speciation minus extinction) rates in the more recent past of mammalian evolution could not be determined. In this paper, I provide a method that reveals that the tempo of mammalian evolution did not change until ∼ 33 Mya. This constant period was followed by a peak of diversification rates between 33 and 30 Mya. Thereafter, diversification rates remained high and constant until 8.55 Mya. Diversification rates declined significantly at 8.55 and 3.35 Mya. Investigation of mammalian subgroups (marsupials, placentals, and the six largest placental subgroups) reveals that the diversification rate peak at 33-30 Mya is mainly driven by rodents, cetartiodactyla, and marsupials. The recent diversification rate decrease is significant for all analyzed subgroups but eulipotyphla, cetartiodactyla, and primates. My likelihood approach is not limited to mammalian evolution. It provides a robust framework to infer diversification rate changes and mass extinction events in phylogenies, reconstructed from, e.g., present-day species or virus data. In particular, the method is very robust toward noise and uncertainty in the phylogeny and can account for incomplete taxon sampling. PMID:21444816

  3. Postnatal high-fat diet leads to spatial deficit, obesity, and central and peripheral inflammation in prenatal dexamethasone adult offspring rats.

    PubMed

    Hsieh, Chih-Sung; Li, Shih-Wen; Sheen, Jiunn-Ming; Yu, Hong-Ren; Tiao, Mao-Meng; Tain, You-Lin; Su, Chung-Hao; Huang, Li-Tung

    2016-08-01

    Synthetic glucocorticoids are frequently used in clinical practice for treating pregnant women at risk of preterm delivery, but their long-term effects on the infant brain are largely unknown. Pregnant Sprague-Dawley rats were administered vehicle or dexamethasone between gestational days 14 and 21. Male offspring were then weaned onto either a standard chow or a high-fat diet. The postnatal levels of insulin-like growth factor I (IGF-1), tumor necrosis factor-α (TNF-α), and asymmetric dimethylarginine (ADMA) in the plasma, liver, and brain were examined, as well as the possible effects of prenatal dexamethasone on cognition. We found that a postnatal high-fat diet led to spatial deficits detected by the Morris water maze in adult offspring administered dexamethasone prenatally. The spatial deficit was accompanied by decreased IGF-1 mRNA and increased ADMA levels in the dorsal hippocampus. In peripheral systems, a postnatal high-fat diet resulted in decreased plasma IGF-1, increased plasma corticosterone, increased concentrations of transaminases, TNF-α mRNA, and ADMA in the liver, and associated obesity in adult offspring administered prenatal dexamethasone. In conclusion, a postnatal high-fat diet led to spatial deficits, obesity, and altered levels of IGF-1, TNF-α, and ADMA in the plasma, liver, or brain. PMID:27272689

  4. Endogenous neurogenic cell response in the mature mammalian brain following traumatic injury.

    PubMed

    Sun, Dong

    2016-01-01

    In the mature mammalian brain, new neurons are generated throughout life in the neurogenic regions of the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus. Over the past two decades, extensive studies have examined the extent of adult neurogenesis in the SVZ and DG, the role of the adult generated new neurons in normal brain function and the underlying mechanisms regulating the process of adult neurogenesis. The extent and the function of adult neurogenesis under neuropathological conditions have also been explored in varying types of disease models in animals. Increasing evidence has indicated that these endogenous neural stem/progenitor cells may play regenerative and reparative roles in response to CNS injuries or diseases. This review will discuss the potential functions of adult neurogenesis in the injured brain and will describe the recent development of strategies aimed at harnessing this neurogenic capacity in order to repopulate and repair the injured brain following trauma. PMID:25936874

  5. Adult axolotls can regenerate original neuronal diversity in response to brain injury.

    PubMed

    Amamoto, Ryoji; Huerta, Violeta Gisselle Lopez; Takahashi, Emi; Dai, Guangping; Grant, Aaron K; Fu, Zhanyan; Arlotta, Paola

    2016-01-01

    The axolotl can regenerate multiple organs, including the brain. It remains, however, unclear whether neuronal diversity, intricate tissue architecture, and axonal connectivity can be regenerated; yet, this is critical for recovery of function and a central aim of cell replacement strategies in the mammalian central nervous system. Here, we demonstrate that, upon mechanical injury to the adult pallium, axolotls can regenerate several of the populations of neurons present before injury. Notably, regenerated neurons acquire functional electrophysiological traits and respond appropriately to afferent inputs. Despite the ability to regenerate specific, molecularly-defined neuronal subtypes, we also uncovered previously unappreciated limitations by showing that newborn neurons organize within altered tissue architecture and fail to re-establish the long-distance axonal tracts and circuit physiology present before injury. The data provide a direct demonstration that diverse, electrophysiologically functional neurons can be regenerated in axolotls, but challenge prior assumptions of functional brain repair in regenerative species. PMID:27156560

  6. Long-term effects of early adolescent stress: dysregulation of hypothalamic-pituitary-adrenal axis and central corticotropin releasing factor receptor 1 expression in adult male rats.

    PubMed

    Li, Chuting; Liu, Yuan; Yin, Shiping; Lu, Cuiyan; Liu, Dexiang; Jiang, Hong; Pan, Fang

    2015-07-15

    Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by traumatic experiences. Studies have found that exposure to early stressful events is a risk factor for developing PTSD. However, a limited number of studies have explored the effects of traumatic stress in early adolescence on behavior, hypothalamic-pituitary-adrenal (HPA) axis function, central corticotropin releasing factor receptor 1 (CRFR1) expression and the relative vulnerability of PTSD in adulthood. The current study aims to explore these issues using inescapable electric foot shock to induce a PTSD model in early adolescent rats. Meanwhile, running on a treadmill for six weeks and administration of the antagonist with 3.2mg/kg/day of CP-154, 526 for 14 consecutive days were used as therapeutic measures. Presently, the stress (S) group showed more anxiety and depression in the open field (OF) test and elevated plus maze (EPM) test, memory damage in the Y maze test, decreased basal CORT level, increased DEX negative feedback inhibition and exacerbated and longer-lasting reaction to CRH challenge in the DEX/CRH test compared with the control group. Central CRFR1 expression was also changed in the S group, as evidenced by the increased CRFR1 expression in the hypothalamus, amygdala and the prefrontal cortex (PFC). However, treadmill exercise alleviated early adolescent stress-induced behavior abnormalities and improved the functional state of the HPA axis, performing a more powerful effect than the CRFR1 antagonist CP-154, 526. Additionally, this study revealed that the alteration of central CRFR1 expression might play an important role in etiology of PTSD in adulthood. PMID:25882722

  7. Evolution and development of the mammalian cerebral cortex

    PubMed Central

    Molnár, Zoltán; Kaas, Jon H.; de Carlos, Juan A.; Hevner, Robert F.; Lein, Ed; Němec, Pavel

    2014-01-01

    Comparative developmental studies of the mammalian brain can identify key changes that can generate the diverse structures and functions of brains. We have studied how the neocortex of early mammals became organized into functionally distinct areas, and how the current level of cortical cellular and laminar specialization arose from the simpler premammalian cortex. We demonstrate the neocortical organization in early mammals that is most informative for an understanding of how the large, complex human brain evolved from a long line of ancestors. The radial and tangential enlargement of the cortex was driven by changes in the patterns of cortical neurogenesis, including alterations in the proportions of distinct progenitor types. Some cortical cell populations travel to the cortex through tangential migration, others migrate radially. A number of recent studies have begun to characterize the chick, mouse, human and non-human primate cortical transcriptome to help us understand how gene expression relates to the development, and to the anatomical and functional organization of the adult neocortex. Although all mammalian forms share the basic layout of cortical areas, the areal proportions and distributions are driven by distinct evolutionary pressures acting on sensory and motor experiences during the individual ontogenies. PMID:24776993

  8. Wnt signalling pathway parameters for mammalian cells.

    PubMed

    Tan, Chin Wee; Gardiner, Bruce S; Hirokawa, Yumiko; Layton, Meredith J; Smith, David W; Burgess, Antony W

    2012-01-01

    Wnt/β-catenin signalling regulates cell fate, survival, proliferation and differentiation at many stages of mammalian development and pathology. Mutations of two key proteins in the pathway, APC and β-catenin, have been implicated in a range of cancers, including colorectal cancer. Activation of Wnt signalling has been associated with the stabilization and nuclear accumulation of β-catenin and consequential up-regulation of β-catenin/TCF gene transcription. In 2003, Lee et al. constructed a computational model of Wnt signalling supported by experimental data from analysis of time-dependent concentration of Wnt signalling proteins in Xenopus egg extracts. Subsequent studies have used the Xenopus quantitative data to infer Wnt pathway dynamics in other systems. As a basis for understanding Wnt signalling in mammalian cells, a confocal live cell imaging measurement technique is developed to measure the cell and nuclear volumes of MDCK, HEK293T cells and 3 human colorectal cancer cell lines and the concentrations of Wnt signalling proteins β-catenin, Axin, APC, GSK3β and E-cadherin. These parameters provide the basis for formulating Wnt signalling models for kidney/intestinal epithelial mammalian cells. There are significant differences in concentrations of key proteins between Xenopus extracts and mammalian whole cell lysates. Higher concentrations of Axin and lower concentrations of APC are present in mammalian cells. Axin concentrations are greater than APC in kidney epithelial cells, whereas in intestinal epithelial cells the APC concentration is higher than Axin. Computational simulations based on Lee's model, with this new data, suggest a need for a recalibration of the model.A quantitative understanding of Wnt signalling in mammalian cells, in particular human colorectal cancers requires a detailed understanding of the concentrations of key protein complexes over time. Simulations of Wnt signalling in mammalian cells can be initiated with the parameters

  9. A Cell Line Producing Recombinant Nerve Growth Factor Evokes Growth Responses in Intrinsic and Grafted Central Cholinergic Neurons

    NASA Astrophysics Data System (ADS)

    Ernfors, Patrik; Ebendal, Ted; Olson, Lars; Mouton, Peter; Stromberg, Ingrid; Persson, Hakan

    1989-06-01

    The rat β nerve growth factor (NGF) gene was inserted into a mammalian expression vector and cotransfected with a plasmid conferring resistance to neomycin into mouse 3T3 fibroblasts. From this transfection a stable cell line was selected that contains several hundred copies of the rat NGF gene and produces excess levels of recombinant NGF. Such genetically modified cells were implanted into the rat brain as a probe for in vivo effects of NGF on central nervous system neurons. In a model of the cortical cholinergic deficits in Alzheimer disease, we demonstrate a marked increase in the survival of, and fiber outgrowth from, grafts of fetal basal forebrain cholinergic neurons, as well as stimulation of fiber formation by intact adult intrinsic cholinergic circuits in the cerebral cortex. Adult cholinergic interneurons in intact striatum also sprout vigorously toward implanted fibroblasts. Our results suggest that this model has implications for future treatment of neurodegenerative diseases.

  10. Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting: Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4{sup +} T cells compared

    SciTech Connect

    Ford, A.L.; Goodsall, A.L.; Sedgwick, J.D.

    1995-05-01

    Ramified microglia in the adult central nervous system (CNS) are the principal glial element up-regulating MHC class I and II expression in response to inflammatory events or neuronal damage. A proportion of these cells also express MHC class II constitutively in the normal CNS. The role of microglia as APCs for CD4{sup +} cells extravasating into the CNS remains undefined. In this study, using irradiation bone marrow chimeras in CD45-congenic rats, the phenotype CD45{sup low}CD11b/c{sup +} is shown to identify microglial cells specifically within the CNS. Highly purified populations of microglia and nonmicroglial but CNS-associated macrophages (CD45{sup high}CD11b/c{sup +}) have been obtained directly from the adult CNS, by using flow cytometric sorting. Morphologically, freshly isolated microglia vs other CNS macrophages are quite distinct. Of the two populations recovered from the normal CNS, it is the minority CD45{sup high}CD11 b/c{sup +} transitional macrophage population, and not microglia, that is the effective APC for experimental autoimmune encephalomyelitis-inducing CD4{sup +} myelin basic protein (MBP)-reactive T cells. CD45{sup high}CD11b/c{sup +} CNS macrophages also stimulate MBP-reactive T cells without addition of MBP to culture suggesting presentation of endogenous Ag. This is the first study in which microglia vs other CNS macrophages have been analyzed for APC ability directly from the CNS, with substantial cross-contamination between the two populations eliminated. The heterogeneity of these populations in terms of APC function is clearly demonstrated. Evidence is still lacking that adult CNS microglia have the capacity to interact with and stimulate CD4{sup +} T cells to proliferate or secrete IL-2. 60 refs., 6 figs., 1 tab.

  11. Mammalian Cell-Based Sensor System

    NASA Astrophysics Data System (ADS)

    Banerjee, Pratik; Franz, Briana; Bhunia, Arun K.

    Use of living cells or cellular components in biosensors is receiving increased attention and opens a whole new area of functional diagnostics. The term "mammalian cell-based biosensor" is designated to biosensors utilizing mammalian cells as the biorecognition element. Cell-based assays, such as high-throughput screening (HTS) or cytotoxicity testing, have already emerged as dependable and promising approaches to measure the functionality or toxicity of a compound (in case of HTS); or to probe the presence of pathogenic or toxigenic entities in clinical, environmental, or food samples. External stimuli or changes in cellular microenvironment sometimes perturb the "normal" physiological activities of mammalian cells, thus allowing CBBs to screen, monitor, and measure the analyte-induced changes. The advantage of CBBs is that they can report the presence or absence of active components, such as live pathogens or active toxins. In some cases, mammalian cells or plasma membranes are used as electrical capacitors and cell-cell and cell-substrate contact is measured via conductivity or electrical impedance. In addition, cytopathogenicity or cytotoxicity induced by pathogens or toxins resulting in apoptosis or necrosis could be measured via optical devices using fluorescence or luminescence. This chapter focuses mainly on the type and applications of different mammalian cell-based sensor systems.

  12. A Comparative Study of Mammalian Diversification Pattern

    PubMed Central

    Yu, Wenhua; Xu, Junxiao; Wu, Yi; Yang, Guang

    2012-01-01

    Although mammals have long been regarded as a successful radiation, the diversification pattern among the clades is still poorly known. Higher-level phylogenies are conflicting and comprehensive comparative analyses are still lacking. Using a recently published supermatrix encompassing nearly all extant mammalian families and a novel comparative likelihood approach (MEDUSA), the diversification pattern of mammalian groups was examined. Both order- and family-level phylogenetic analyses revealed the rapid radiation of Boreoeutheria and Euaustralidelphia in the early mammalian history. The observation of a diversification burst within Boreoeutheria at approximately 100 My supports the Long Fuse model in elucidating placental diversification progress, and the rapid radiation of Euaustralidelphia suggests an important role of biogeographic dispersal events in triggering early Australian marsupial rapid radiation. Diversification analyses based on family-level diversity tree revealed seven additional clades with exceptional diversification rate shifts, six of which represent accelerations in net diversification rate as compared to the background pattern. The shifts gave origin to the clades Muridae+Cricetidae, Bovidae+Moschidae+Cervidae, Simiiformes, Echimyidae, Odontoceti (excluding Physeteridae+Kogiidae+Platanistidae), Macropodidae, and Vespertilionidae. Moderate to high extinction rates from background and boreoeutherian diversification patterns indicate the important role of turnovers in shaping the heterogeneous taxonomic richness observed among extant mammalian groups. Furthermore, the present results emphasize the key role of extinction on erasing unusual diversification signals, and suggest that further studies are needed to clarify the historical radiation of some mammalian groups for which MEDUSA did not detect exceptional diversification rates. PMID:22457604

  13. Identification of Radial Glia Progenitors in the Developing and Adult Retina of Sharks

    PubMed Central

    Sánchez-Farías, Nuria; Candal, Eva

    2016-01-01

    Neural stem cells give rise to transient progenitors termed neuroepithelial cells (NECs) and radial glial cells (RGCs). RGCs represent the major source of neurons, glia and adult stem cells in several regions of the central nervous system (CNS). RGCs are mostly transient in mammals, but they are widely maintained in the adult CNS of fishes, where they continue to be morphologically similar to RGCs in the mammalian brain and fulfill similar roles as progenitors and guide for migrating neurons. The retina of fishes offers an exceptional model to approach the study of adult neurogenesis because of the presence of constitutive proliferation from the ciliary marginal zone (CMZ), containing NECs, and from adult glial cells with radial morphology (the Müller glia). However, the cellular hierarchies and precise contribution of different types of progenitors to adult neurogenesis remain unsolved. We have analyzed the transition from NECs to RGCs and RGC differentiation in the retina of the cartilaginous fish Scyliorhinus canicula, which offers a particularly good spatial and temporal frame to investigate this process. We have characterized progenitor and adult RGCs by immunohistochemical detection of glial markers as glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS). We have compared the emergence and localization of glial markers with that of proliferating cell nuclear antigen (PCNA, a proliferation maker) and Doublecortin (DCX, which increases at early stages of neuronal differentiation). During retinal development, GFAP-immunoreactive NECs located in the most peripheral CMZ (CMZp) codistribute with DCX-immunonegative cells. GFAP-immunoreactive RGCs and Müller cells are located in successive more central parts of the retina and codistribute with DCX- and DCX/GS-immunoreactive cells, respectively. The same types of progenitors are found in juveniles, suggesting that the contribution of the CMZ to adult neurogenesis implies a transition through the

  14. Implementation of routine counselor-initiated opt-out HIV testing on the adult medical ward at Kamuzu Central Hospital, Lilongwe, Malawi

    PubMed Central

    LaCourse, Sylvia M.; Chester, Frances M.; Matoga, Mitch; Munthali, Charles; Nsona, Dominic; Haac, Bryce; Hoffman, Irving F.; Hosseinipour, Mina C.

    2015-01-01

    The optimal approach of provider-initiated HIV testing and counseling (PITC) for inpatients in high-burden settings is unknown. We prospectively evaluated the implementation of task-shifting from clinician-referral to counselor-initiated PITC on the medical wards of Kamuzu Central Hospital, Malawi. The majority of patients (1905/3154, 60.4%) had an unknown admission HIV status. Counselors offered testing to 66.6% (1268/1905). HIV prevalence was 39.3%. Counselor-initiated PITC significantly increased HIV testing by 79% (643/2957 vs. 1228/3154), resulting in an almost 2-fold increase in patients with known HIV status (2447/3154 vs. 1249/3154) (both p<.0001), with 18.4% of those tested receiving a new diagnosis of HIV. PMID:25622063

  15. CENTRAL 5-ALPHA REDUCTION OF TESTOSTERONE IS REQUIRED FOR TESTOSTERONE’S INHIBITION OF THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS RESPONSE TO RESTRAINT STRESS IN ADULT MALE RATS

    PubMed Central

    Handa, Robert J.; Kudwa, Andrea E.; Donner, Nina C.; McGivern, Robert F.; Brown, Roger

    2013-01-01

    In rodents, the hypothalamo-pituitary-adrenal (HPA) axis is controlled by a precise regulatory mechanism that is influenced by circulating gonadal and adrenal hormones. In males, gonadectomy increases the adrenocorticotropic hormone (ACTH) and corticosterone (CORT) response to stressors, and androgen replacement returns the response to that of the intact male. Testosterone (T) actions in regulating HPA activity may be through aromatization to estradiol, or by 5α-reduction to the more potent androgen, dihydrotestosterone (DHT). To determine if the latter pathway is involved, we assessed the function of the HPA axis response to restraint stress following hormone treatments, or after peripheral or central treatment with the 5α-reductase inhibitor, finasteride. Initially, we examined the timecourse whereby gonadectomy alters the CORT response to restraint stress. Enhanced CORT responses were evident within 48hrs following gonadectomy. Correspondingly, treatment of intact male rats with the 5α-reductase inhibitor, finasteride, for 48 hrs, enhanced the CORT and ACTH response to restraint stress. Peripheral injections of gonadectomized male rats with DHT or T for 48 hrs reduced the ACTH and CORT response to restraint stress. The effects of T, but not DHT, could be blocked by the third ventricle administration of finasteride prior to stress application. These data indicate that the actions of T in modulating HPA axis activity involve 5α-reductase within the central nervous system. These results further our understanding of how T acts to modulate the neuroendocrine stress responses and indicate that 5α reduction to DHT is a necessary step for T action. PMID:23880372

  16. Central 5-alpha reduction of testosterone is required for testosterone's inhibition of the hypothalamo-pituitary-adrenal axis response to restraint stress in adult male rats.

    PubMed

    Handa, Robert J; Kudwa, Andrea E; Donner, Nina C; McGivern, Robert F; Brown, Roger

    2013-09-01

    In rodents, the hypothalamo-pituitary-adrenal (HPA) axis is controlled by a precise regulatory mechanism that is influenced by circulating gonadal and adrenal hormones. In males, gonadectomy increases the adrenocorticotropic hormone (ACTH) and corticosterone (CORT) response to stressors, and androgen replacement returns the response to that of the intact male. Testosterone (T) actions in regulating HPA activity may be through aromatization to estradiol, or by 5α-reduction to the more potent androgen, dihydrotestosterone (DHT). To determine if the latter pathway is involved, we assessed the function of the HPA axis response to restraint stress following hormone treatments, or after peripheral or central treatment with the 5α-reductase inhibitor, finasteride. Initially, we examined the timecourse whereby gonadectomy alters the CORT response to restraint stress. Enhanced CORT responses were evident within 48 h following gonadectomy. Correspondingly, treatment of intact male rats with the 5α-reductase inhibitor, finasteride, for 48 h, enhanced the CORT and ACTH response to restraint stress. Peripheral injections of gonadectomized male rats with DHT or T for 48 h reduced the ACTH and CORT response to restraint stress. The effects of T, but not DHT, could be blocked by the third ventricle administration of finasteride prior to stress application. These data indicate that the actions of T in modulating HPA axis activity involve 5α-reductase within the central nervous system. These results further our understanding of how T acts to modulate the neuroendocrine stress responses and indicate that 5α reduction to DHT is a necessary step for T action. PMID:23880372

  17. Electric fences to reduce mammalian predation on waterfowl nests

    USGS Publications Warehouse

    Lokemoen, J.T.; Doty, H.A.; Sharp, D.E.; Neaville, J.E.

    1982-01-01

    We evaluated electric fences as predator barriers to reduce high losses of waterfowl nests to mammalian predation at Waterfowl Production Areas (WPAs). The work was done in 1978-81 on 3 paired sites in central North Dakota and western Minnesota. Resident mammalian predators were trapped from inside the exclosures. All 3 fences operated during the study period with few major maintenance problems. Nest success in the exclosures was 65% in North Dakota and 55% in Minnesota vs. 45 and 12% in the respective controls. Cover inside the electric fence produced 7.8 more young/ha than cover in control plots in North Dakota during the 3 years. Cover inside the 2 electric fences in Minnesota yielded 9.5 and 4.3 more young/ha than cover in control plots during the 3 years. Using construction costs only we estimated that each additional duckling produced in cover protected by electric fencing cost $0.65 in North Dakota and $0.87 in Minnesota.

  18. Undetectable histone O-GlcNAcylation in mammalian cells.

    PubMed

    Gagnon, Jessica; Daou, Salima; Zamorano, Natalia; Iannantuono, Nicholas V G; Hammond-Martel, Ian; Mashtalir, Nazar; Bonneil, Eric; Wurtele, Hugo; Thibault, Pierre; Affar, El Bachir

    2015-01-01

    O-GlcNAcylation is a posttranslational modification catalyzed by the O-Linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and reversed by O-GlcNAcase (OGA). Numerous transcriptional regulators, including chromatin modifying enzymes, transcription factors, and co-factors, are targeted by O-GlcNAcylation, indicating that this modification is central for chromatin-associated processes. Recently, OGT-mediated O-GlcNAcylation was reported to be a novel histone modification, suggesting a potential role in directly coordinating chromatin structure and function. In contrast, using multiple biochemical approaches, we report here that histone O-GlcNAcylation is undetectable in mammalian cells. Conversely, O-GlcNAcylation of the transcription regulators Host Cell Factor-1 (HCF-1) and Ten-Eleven Translocation protein 2 (TET2) could be readily observed. Our study raises questions on the occurrence and abundance of O-GlcNAcylation as a histone modification in mammalian cells and reveals technical complications regarding the detection of genuine protein O-GlcNAcylation. Therefore, the identification of the specific contexts in which histone O-GlcNAcylation might occur is still to be established. PMID:26075789

  19. RNAi pathway participates in chromosome segregation in mammalian cells

    PubMed Central

    Huang, Chuan; Wang, Xiaolin; Liu, Xu; Cao, Shuhuan; Shan, Ge

    2015-01-01

    The RNAi machinery is a mighty regulator in a myriad of life events. Despite lines of evidence that small RNAs and components of the RNAi pathway may be associated with structure and behavior of mitotic chromosomes in diverse organisms, a direct role of the RNAi pathway in mammalian mitotic chromosome segregation remains elusive. Here we report that Dicer and AGO2, two central components of the mammalian RNAi pathway, participate in the chromosome segregation. Knockdown of Dicer or AGO2 results in a higher incidence of chromosome lagging, and this effect is independent from microRNAs as examined with DGCR8 knockout cells. Further investigation has revealed that α-satellite RNA, a noncoding RNA derived from centromeric repeat region, is managed by AGO2 under the guidance of endogenous small interference RNAs (ASAT siRNAs) generated by Dicer. Furthermore, the slicer activity of AGO2 is essential for the chromosome segregation. Level and distribution of chromosome-associated α-satellite RNA have crucial regulatory effect on the localization of centromeric proteins such as centromere protein C1 (CENPC1). With these results, we also provide a paradigm in which the RNAi pathway participates in vital cellular events through the maintenance of level and distribution of noncoding RNAs in cells.

  20. Biochemistry of growth inhibition by ammonium ions in mammalian cells

    SciTech Connect

    Ryll, T.; Valley, U.; Wagner, R. . Cell Culture Techniques Dept.)

    1994-06-20

    The intracellular pool of UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine has been shown to act as a central target during the inhibitory action of ammonium ions in vitro cultivated mammalian cell cultures. This pool has been demonstrated to be elevated at the end of a batch cultivation and very quickly as a response to exogenously applied ammonium chloride by using four different cell lines (hybridoma, BHK, CHO, and Ltk-929). The amount of enlarged UDP aminohexoses is correlated to the inhibitor concentration and additionally dependent on the cell line. The formation of the UDP sugars is associated with a transient reduction of the UTP pool. Moreover, the quick formation of UDP-GNAC is strictly dependent on the presence of, glucose and ammonium. Both metabolites act as biochemical precursors. Additionally, the formation of UDP-GNAc after ammonium application has been shown to increase with an elevated cultivation pH and to be independent of the inhibition of transcription and translation processes. The intracellular amount of UDP-GNAc correlates with the level of growth inhibition in mammalian cell lines.

  1. 5-Hydroxymethylcytosine – the elusive epigenetic mark in mammalian DNA

    PubMed Central

    Kriukienė, Edita; Liutkevičiūtė, Zita

    2012-01-01

    Over the past decade, epigenetic phenomena claimed a central role in cell regulatory processes and proved important factors for understanding complex human diseases. One of the best understood epigenetic mechanisms is DNA methylation. In the mammalian genome, cytosines (C) were long known to exist in two functional states: unmethylated or methylated at the 5-position of the pyrimidine ring (5mC). Recent studies of genomic DNA from the human and mouse brain, neurons and from mouse embryonic stem cells found that a substantial fraction of 5mC in CpG dinucleotides is converted to 5-hydroxymethyl-cytosine (hmC) by the action of 2-oxoglutarate- and Fe(II)-dependent oxygenases of the TET family. These findings provided important clues in a long elusive mechanism of active DNA demethylation and bolstered a fresh wave of studies in the area of epigenetic regulation in mammals. This 15 review is dedicated to critical assessment of the most popular techniques with respect to their suitability for analysis of hmC in mammalian genomes. It also discusses the most recent data on biochemical and chemical aspects of the formation and further conversion of this nucleobase in DNA and its possible biological roles in cell differentiation, embryogenesis and brain function. PMID:22842880

  2. Axonal injury and regeneration in the adult brain of Drosophila

    PubMed Central

    Ayaz, Derya; Leyssen, Maarten; Koch, Marta; Yan, Jiekun; Srahna, Mohammed; Sheeba, Vasu; Fogle, Keri J.; Holmes, Todd C.; Hassan, Bassem A.

    2009-01-01

    Drosophila melanogaster is a leading genetic model system in nervous system development and disease research. Using the power of fly genetics in traumatic axonal injury research will significantly speed up the characterization of molecular processes that control axonal regeneration in the Central Nervous System (CNS). We developed a versatile and physiologically robust preparation for the long-term culture of the whole Drosophila brain. We use this method to develop a novel Drosophila model for CNS axonal injury and regeneration. We first show that, similar to mammalian CNS axons, injured adult wild type fly CNS axons fail to regenerate, whereas adult-specific enhancement of Protein Kinase A activity increases the regenerative capacity of lesioned neurons. Combined, these observations suggest conservation of neuronal regeneration mechanisms following injury. We next exploit this model to explore pathways that induce robust regeneration and find that adult-specific activation of JNK signalling is sufficient for de novo CNS axonal regeneration after injury, including the growth of new axons past the lesion site and into the normal target area. PMID:18524906

  3. BMI, HOMA-IR, and Fasting Blood Glucose Are Significant Predictors of Peripheral Nerve Dysfunction in Adult Overweight and Obese Nondiabetic Nepalese Individuals: A Study from Central Nepal

    PubMed Central

    Thapa, Lekhjung; Rana, P. V. S.

    2016-01-01

    Objective. Nondiabetic obese individuals have subclinical involvement of peripheral nerves. We report the factors predicting peripheral nerve function in overweight and obese nondiabetic Nepalese individuals. Methodology. In this cross-sectional study, we included 50 adult overweight and obese nondiabetic volunteers without features of peripheral neuropathy and 50 healthy volunteers to determine the normative nerve conduction data. In cases of abnormal function, the study population was classified on the basis of the number of nerves involved, namely, “<2” or “≥2.” Multivariable logistic regression analysis was carried out to predict outcomes. Results. Fasting blood glucose (FBG) was the significant predictor of motor nerve dysfunction (P = 0.039, 95% confidence interval (CI) = 1.003–1.127). Homeostatic model assessment of insulin resistance (HOMA-IR) was the significant predictor (P = 0.019, 96% CI = 1.420–49.322) of sensory nerve dysfunction. Body mass index (BMI) was the significant predictor (P = 0.034, 95% CI = 1.018–1.577) in case of ≥2 mixed nerves' involvement. Conclusion. FBG, HOMA-IR, and BMI were significant predictors of peripheral nerve dysfunction in overweight and obese Nepalese individuals. PMID:27200189

  4. BMI, HOMA-IR, and Fasting Blood Glucose Are Significant Predictors of Peripheral Nerve Dysfunction in Adult Overweight and Obese Nondiabetic Nepalese Individuals: A Study from Central Nepal.

    PubMed

    Thapa, Lekhjung; Rana, P V S

    2016-01-01

    Objective. Nondiabetic obese individuals have subclinical involvement of peripheral nerves. We report the factors predicting peripheral nerve function in overweight and obese nondiabetic Nepalese individuals. Methodology. In this cross-sectional study, we included 50 adult overweight and obese nondiabetic volunteers without features of peripheral neuropathy and 50 healthy volunteers to determine the normative nerve conduction data. In cases of abnormal function, the study population was classified on the basis of the number of nerves involved, namely, "<2" or "≥2." Multivariable logistic regression analysis was carried out to predict outcomes. Results. Fasting blood glucose (FBG) was the significant predictor of motor nerve dysfunction (P = 0.039, 95% confidence interval (CI) = 1.003-1.127). Homeostatic model assessment of insulin resistance (HOMA-IR) was the significant predictor (P = 0.019, 96% CI = 1.420-49.322) of sensory nerve dysfunction. Body mass index (BMI) was the significant predictor (P = 0.034, 95% CI = 1.018-1.577) in case of ≥2 mixed nerves' involvement. Conclusion. FBG, HOMA-IR, and BMI were significant predictors of peripheral nerve dysfunction in overweight and obese Nepalese individuals. PMID:27200189

  5. Capacitation-Associated Glycocomponents of Mammalian Sperm.

    PubMed

    Liu, Min

    2016-05-01

    Mammalian fertilization is a series of events that are mostly carbohydrate mediated. The male gamete glycocomponents are extensively synthesized and modified during sperm development and sperm transport in the reproductive tracts. Freshly ejaculated mammalian sperm are required to undergo capacitation, which takes place in the female reproductive system, in order to become fully fertilizable. Several lines of evidence reveal changes in glycosylated sperm constituents during capacitation. Although the contributions of these molecular changes to capacitation are not completely understood, the presence, rearrangement, and/or modification of these sperm glycocomponents have been demonstrated to be important for fertilization. The following review summarizes mammalian sperm glycoconstituents, with emphasis on their molecular changes during capacitation. PMID:26363036

  6. Involvement of opsins in mammalian sperm thermotaxis

    PubMed Central

    Pérez-Cerezales, Serafín; Boryshpolets, Sergii; Afanzar, Oshri; Brandis, Alexander; Nevo, Reinat; Kiss, Vladimir; Eisenbach, Michael

    2015-01-01

    A unique characteristic of mammalian sperm thermotaxis is extreme temperature sensitivity, manifested by the capacity of spermatozoa to respond to temperature changes of <0.0006 °C as they swim their body-length distance. The identity of the sensing system that confers this exceptional sensitivity on spermatozoa is not known. Here we show that the temperature-sensing system of mammalian spermatozoa involves opsins, known to be G-protein-coupled receptors that act as photosensors in vision. We demonstrate by molecular, immunological, and functional approaches that opsins are present in human and mouse spermatozoa at specific sites, which depend on the species and the opsin type, and that they are involved in sperm thermotaxis via two signalling pathways—the phospholipase C and the cyclic-nucleotide pathways. Our results suggest that, depending on the context and the tissue, mammalian opsins act not only as photosensors but also as thermosensors. PMID:26537127

  7. Toward predictive models of mammalian cells.

    PubMed

    Ma'ayan, Avi; Blitzer, Robert D; Iyengar, Ravi

    2005-01-01

    Progress in experimental and theoretical biology is likely to provide us with the opportunity to assemble detailed predictive models of mammalian cells. Using a functional format to describe the organization of mammalian cells, we describe current approaches for developing qualitative and quantitative models using data from a variety of experimental sources. Recent developments and applications of graph theory to biological networks are reviewed. The use of these qualitative models to identify the topology of regulatory motifs and functional modules is discussed. Cellular homeostasis and plasticity are interpreted within the framework of balance between regulatory motifs and interactions between modules. From this analysis we identify the need for detailed quantitative models on the basis of the representation of the chemistry underlying the cellular process. The use of deterministic, stochastic, and hybrid models to represent cellular processes is reviewed, and an initial integrated approach for the development of large-scale predictive models of a mammalian cell is presented. PMID:15869393

  8. Effect of Microgravity on Mammalian Lymphocytes

    NASA Technical Reports Server (NTRS)

    Banerjee, H.; Blackshear, M.; Mahaffey, K.; Knight, C.; Khan, A. A.; Delucas, L.

    2004-01-01

    The effect of microgravity on mammalian system is an important and interesting topic for scientific investigation, since NASA s objective is to send manned flights to planets like Mars and eventual human colonization.The Astronauts will be exposed to microgravity environment for a long duration of time during these flights.Our objective of research is to conduct in vitro studies for the effect of microgravity on mammalian immune system.We did our preliminary investigations by exposing mammalian lymphocytes to a microgravity simulator cell bioreactor designed by NASA and manufactured at Synthecon Inc (USA).Our initial results showed no significant change in cytokine expression in these cells for a time period of forty eight hours exposure.Our future experiments will involve exposure for a longer period of time.

  9. Effect of Microgravity on Mammalian Lymphocytes

    NASA Technical Reports Server (NTRS)

    Banerjee, H.; Blackshear, M.; Mahaffey, K.; Khan, A. A.; Delucas, L.

    2004-01-01

    The effect of microgravity on mammalian system is an important and interesting topic for scientific investigation, since NASA s objective is to send manned flights to planets like Mars and eventual human colonization. The Astronauts will be exposed to microgravity environment for a long duration of time during these flights. Our objective of research is to conduct in vitro studies for the effect of microgravity on mammalian immune system and nervous system. We did our preliminary investigations by exposing mammalian lymphocytes and astrocyte cells to a microgravity simulator cell bioreactor designed by NASA and manufactured at Synthecon, Inc. (USA).Our initial results showed no significant change in cytokine expression in these cells up to a time period of 120 hours exposure. Our future experiments will involve exposure for a longer period of time.

  10. Regional patterns of postglacial changes in the Palearctic mammalian diversity indicate retreat to Siberian steppes rather than extinction.

    PubMed

    Pavelková Řičánková, Věra; Robovský, Jan; Riegert, Jan; Zrzavý, Jan

    2015-01-01

    We examined the presence of possible Recent refugia of Pleistocene mammalian faunas in Eurasia by analysing regional differences in the mammalian species composition, occurrence and extinction rates between Recent and Last Glacial faunas. Our analyses revealed that most of the widespread Last Glacial species have survived in the central Palearctic continental regions, most prominently in Altai-Sayan (followed by Kazakhstan and East European Plain). The Recent Altai-Sayan and Kazakhstan regions show species compositions very similar to their Pleistocene counterparts. The Palearctic regions have lost 12% of their mammalian species during the last 109,000 years. The major patterns of the postglacial changes in Palearctic mammalian diversity were not extinctions but rather radical shifts of species distribution ranges. Most of the Pleistocene mammalian fauna retreated eastwards, to the central Eurasian steppes, instead of northwards to the Arctic regions, considered Holocene refugia of Pleistocene megafauna. The central Eurasian Altai and Sayan mountains could thus be considered a present-day refugium of the Last Glacial biota, including mammals. PMID:26246136

  11. Regional patterns of postglacial changes in the Palearctic mammalian diversity indicate retreat to Siberian steppes rather than extinction

    PubMed Central

    Řičánková, Věra Pavelková; Robovský, Jan; Riegert, Jan; Zrzavý, Jan

    2015-01-01

    We examined the presence of possible Recent refugia of Pleistocene mammalian faunas in Eurasia by analysing regional differences in the mammalian species composition, occurrence and extinction rates between Recent and Last Glacial faunas. Our analyses revealed that most of the widespread Last Glacial species have survived in the central Palearctic continental regions, most prominently in Altai–Sayan (followed by Kazakhstan and East European Plain). The Recent Altai–Sayan and Kazakhstan regions show species compositions very similar to their Pleistocene counterparts. The Palearctic regions have lost 12% of their mammalian species during the last 109,000 years. The major patterns of the postglacial changes in Palearctic mammalian diversity were not extinctions but rather radical shifts of species distribution ranges. Most of the Pleistocene mammalian fauna retreated eastwards, to the central Eurasian steppes, instead of northwards to the Arctic regions, considered Holocene refugia of Pleistocene megafauna. The central Eurasian Altai and Sayan mountains could thus be considered a present-day refugium of the Last Glacial biota, including mammals. PMID:26246136

  12. The mammalian blastema: regeneration at our fingertips

    PubMed Central

    Simkin, Jennifer; Sammarco, Mimi C.; Dawson, Lindsay A.; Schanes, Paula P.; Yu, Ling

    2015-01-01

    Abstract In the mouse, digit tip regeneration progresses through a series of discrete stages that include inflammation, histolysis, epidermal closure, blastema formation, and redifferentiation. Recent studies reveal how each regenerative stage influences subsequent stages to establish a blastema that directs the successful regeneration of a complex mammalian structure. The focus of this review is on early events of healing and how an amputation wound transitions into a functional blastema. The stepwise formation of a mammalian blastema is proposed to provide a model for how specific targeted treatments can enhance regenerative performance in humans.

  13. Epigenetic Regulation of Mammalian Stem Cells

    PubMed Central

    Li, Xuekun

    2008-01-01

    Two critical properties of stem cells are self-renewal and multipotency. The maintenance of their “stemness” state and commitment to differentiation are therefore tightly controlled by intricate molecular networks. Epigenetic mechanisms, including DNA methylation, chromatin remodeling and the noncoding RNA-mediated process, have profound regulatory roles in mammalian gene expression. Recent studies have shown that epigenetic regulators are key players in stem cell biology and their dysfunction can result in human diseases such as cancer and neurodevelopmental disorders. Here, we review the recent evidences that advance our knowledge in epigenetic regulations of mammalian stem cells, with focus on embryonic stem cells and neural stem cells. PMID:18393635

  14. Detection of apoptosis in mammalian development.

    PubMed

    Lin, Lin; Penaloza, Carlos; Ye, Yixia; Lockshin, Richard A; Zakeri, Zahra

    2009-01-01

    Mammalian development is dependent on an intricate orchestration of cell proliferation and death. Deregulation in the levels, localization, and type of cell death can lead to disease and even death of the developing embryo. The mechanisms involved in such deregulation are many; alterations and or manipulations of these can aid in the detection, prevention and possible treatments of any effects this de-regulation may have. Here we describe how cell death can be detected during mammalian development, using diverse staining and microscopy methods, while taking advantage of the advancements in cell death mechanisms, derived from biochemical and teratological studies in the field. PMID:19609762

  15. The DeMSTification of mammalian Ste20 kinases.

    PubMed

    Radu, Maria; Chernoff, Jonathan

    2009-05-26

    When first reported in 1995, the mammalian Ste20-like kinases (Mst) 1 and 2 were so named both for their similarity to the yeast kinase Ste20 and for the fact that their function was, to us, a deep mystery. While much remains to be explained about the regulation and role of these kinases, the veil has been at least partly raised on the Msts, revealing unexpected modes of activation and function. Work in model organisms suggests a central growth-suppressive role for Mst orthologs, with intriguing possible links to other established tumor suppressors. This minireview underlines our current understanding of how Mst1 and Mst2 are regulated, and how activation of these proteins influences cell survival and proliferation. PMID:19467213

  16. The relationship of prenatal ethanol exposure and anxiety-related behaviors and central androgen receptor and vasopressin expression in adult male mandarin voles.

    PubMed

    He, F

    2014-04-25

    Prenatal exposure to ethanol has been shown to increase the risk of anxiety in offspring. Here, we tested the effect of prenatal ethanol exposure on adult male mandarin voles (Microtus mandarinus). We examined anxiety-like behavior in the open field and elevated plus-maze tests in males exposed to ethanol prenatally. One control group was not exposed to ethanol or saline, while another control group was exposed to saline. At the age of 90days, males were tested and levels of serum testosterone, androgen receptor immunoreactive neurons (AR-IRs) and arginine vasopressin immunoreactive neurons (AVP-IRs) were measured. Animals exposed to ethanol spent less time in the center of the chamber, covered less distance and conducted fewer crossings in the open-field test. These animals also spent less time and conducted fewer crossings in the open arms. However, they spent more time and made more entries in the closed arms, and traveled less total distance during the elevated plus-maze test, compared to the control voles. Serum T was lower in the ethanol group, and the AR-IR number in the bed nucleus of the stria terminalis (BNST), medial preoptic area (mPOA) and medial amygdaloid nucleus (MeA) was significantly lower. The number of AVP-IRs in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the ethanol group was higher than that of the control groups. Our findings suggest that prenatal ethanol exposure may lead to reduced serum T levels, decreased AR and increased AVP in the CNS and result in the development of anxiety-like behaviors. PMID:24583039

  17. Functional neurogenesis in the adult hippocampus

    NASA Astrophysics Data System (ADS)

    van Praag, Henriette; Schinder, Alejandro F.; Christie, Brian R.; Toni, Nicolas; Palmer, Theo D.; Gage, Fred H.

    2002-02-01

    There is extensive evidence indicating that new neurons are generated in the dentate gyrus of the adult mammalian hippocampus, a region of the brain that is important for learning and memory. However, it is not known whether these new neurons become functional, as the methods used to study adult neurogenesis are limited to fixed tissue. We use here a retroviral vector expressing green fluorescent protein that only labels dividing cells, and that can be visualized in live hippocampal slices. We report that newly generated cells in the adult mouse hippocampus have neuronal morphology and can display passive membrane properties, action potentials and functional synaptic inputs similar to those found in mature dentate granule cells. Our findings demonstrate that newly generated cells mature into functional neurons in the adult mammalian brain.

  18. A prospective study of magnetic resonance imaging patterns of central nervous system infections in pediatric age group and young adults and their clinico-biochemical correlation

    PubMed Central

    Gupta, Kamini; Banerjee, Avik; Saggar, Kavita; Ahluwalia, Archana; Saggar, Karan

    2016-01-01

    Background: Infections of the central nervous system (CNS) are common and routinely encountered. Our aim was to evaluate the neuroimaging features of the various infections of the CNS so as to differentiate them from tumoral, vascular, and other entities that warrant a different line of therapy. Aims: Our aim was to analyze the biochemical and magnetic resonance imaging (MRI) features in CNS infections. Settings and Design: This was a longitudinal, prospective study over a period of 1½ years. Subjects and Methods: We studied cerebrospinal fluid (CSF) findings and MRI patterns in 27 patients of 0–20 years age group with clinical features of CNS infections. MRI was performed on MAGNETOM Avanto 18 Channel 1.5 Tesla MR machine by Siemens India Ltd. The MRI protocol consisted of diffusion-weighted and apparent diffusion coefficient imaging, turbo spin echo T2-weighted, spin echo T1-weighted, fluid-attenuated inversion recovery (FLAIR), and gradient-echo in axial, FLAIR in coronal, and T2-weighted in sagittal plane. Contrast-enhanced T1-weighted sequence and MR spectroscopy were done whenever indicated. Results and Conclusions: We found that most of the children belong to 1–10 years age group. Fungal infections were uncommon, mean CSF adenosine deaminase values specific for tuberculosis and mean CSF glucose-lowered in pyogenic. Hemorrhagic involvement of thalamus with/without basal ganglia and brainstem involvement may indicate Japanese encephalitis or dengue encephalitis. Diffusion restriction or hemorrhage in not expected in the brainstem afflicted lesions of rabies. Congenital cytomegalovirus can cause cortical malformations. T1 hyperintensities with diffusion restriction may represent viral encephalitis. Lesions of acute disseminated encephalomyelitis (ADEM) may mimic viral encephalitis. Leptomeningeal enhancement is predominant in pyogenic meningitis. Basilar meningitis in the presence of tuberculomas is highly sensitive and specific for tuberculosis. PMID

  19. Intra-Operative Fluid Management in Adult Neurosurgical Patients Undergoing Intracranial Tumour Surgery: Randomised Control Trial Comparing Pulse Pressure Variance (PPV) and Central Venous Pressure (CVP)

    PubMed Central

    Salins, Serina Ruth; Kumar, Amar Nandha; Korula, Grace

    2016-01-01

    Introduction Fluid management in neurosurgery presents specific challenges to the anaesthesiologist. Dynamic para-meters like Pulse Pressure Variation (PPV) have been used successfully to guide fluid management. Aim To compare PPV against Central Venous Pressure (CVP) in neurosurgical patients to assess hemodynamic stability and perfusion status. Materials and Methods This was a single centre prospective randomised control trial at a tertiary care centre. A total of 60 patients undergoing intracranial tumour excision in supine and lateral positions were randomised to two groups (Group 1, CVP n=30), (Group 2, PPV n=30). Intra-operative fluid management was titrated to maintain baseline CVP in Group 1(5-10cm of water) and in Group 2 fluids were given to maintain PPV less than 13%. Acid base status, vital signs and blood loss were monitored. Results Although intra-operative hypotension and acid base changes were comparable between the groups, the patients in the CVP group had more episodes of hypotension requiring fluid boluses in the first 24 hours post surgery. {CVP group median (25, 75) 2400ml (1850, 3110) versus PPV group 2100ml (1350, 2200) p=0.03} The patients in the PPV group received more fluids than the CVP group which was clinically significant. {2250 ml (1500, 3000) versus 1500ml (1200, 2000) median (25, 75) (p=0.002)}. The blood loss was not significantly different between the groups The median blood loss in the CVP group was 600ml and in the PPV group was 850 ml; p value 0.09. Conclusion PPV can be used as a reliable index to guide fluid management in neurosurgical patients undergoing tumour excision surgery in supine and lateral positions and can effectively augment CVP as a guide to fluid management. Patients in PPV group had better hemodynamic stability and less post operative fluid requirement. PMID:27437329

  20. Characterization of Proliferating Neural Progenitors after Spinal Cord Injury in Adult Zebrafish

    PubMed Central

    Hui, Subhra Prakash; Nag, Tapas Chandra; Ghosh, Sukla

    2015-01-01

    Zebrafish can repair their injured brain and spinal cord after injury unlike adult mammalian central nervous system. Any injury to zebrafish spinal cord would lead to increased proliferation and neurogenesis. There are presences of proliferating progenitors from which both neuronal and glial loss can be reversed by appropriately generating new neurons and glia. We have demonstrated the presence of multiple progenitors, which are different types of proliferating populations like Sox2+ neural progenitor, A2B5+ astrocyte/ glial progenitor, NG2+ oligodendrocyte progenitor, radial glia and Schwann cell like progenitor. We analyzed the expression levels of two common markers of dedifferentiation like msx-b and vimentin during regeneration along with some of the pluripotency associated factors to explore the possible role of these two processes. Among the several key factors related to pluripotency, pou5f1 and sox2 are upregulated during regeneration and associated with activation of neural progenitor cells. Uncovering the molecular mechanism for endogenous regeneration of adult zebrafish spinal cord would give us more clues on important targets for future therapeutic approach in mammalian spinal cord repair and regeneration. PMID:26630262

  1. The cytogenetics of mammalian autosomal rearrangements

    SciTech Connect

    Daniel, A.

    1988-01-01

    Combining data from animal and clinical studies with classical cytogenetic observations, the volume provides information on various aspects of mammalian autosomal rearrangements. Topics range from the reproductive consequences to carriers of autosomal rearrangements to the application of structural rearrangements and DNA probes to gene mapping. In addition, the book presents an overview of new perspectives and future directions for research.

  2. Mammalian PGRPs also mind the fort.

    PubMed

    Rubino, Stephen; Lee, Jooeun; Girardin, Stephen E

    2010-08-19

    Peptidoglycan recognition proteins (PGRPs or Pglyrps) regulate antibacterial responses in Drosophila, yet their functions in humans remain unclear. In this issue of Cell Host & Microbe, Saha and colleagues report that mammalian PGRPs can prevent aberrant interferon-gamma--induced inflammatory damage in vivo by modulating the composition of the intestinal bacterial flora. PMID:20709290

  3. Architecture of mammalian respiratory complex I

    PubMed Central

    Hirst, Judy

    2014-01-01

    Complex I (NADH:ubiquinone oxidoreductase) is essential for oxidative phosphorylation in mammalian mitochondria. It couples electron transfer from NADH to ubiquinone with proton translocation across the energy-transducing inner membrane, providing electrons for respiration and driving ATP synthesis. Mammalian complex I contains 44 different nuclear- and mitochondrial-encoded subunits, with a combined mass of 1 MDa. The fourteen conserved ‘core’ subunits have been structurally defined in the minimal, bacterial complex, but the structures and arrangement of the 30 ‘supernumerary’ subunits are unknown. Here, we describe a 5 Å resolution structure of complex I from Bos taurus heart mitochondria, a close relative of the human enzyme, determined by single-particle electron cryo-microscopy. We present the structures of the mammalian core subunits that contain eight iron-sulphur clusters and 60 transmembrane helices, identify 18 supernumerary transmembrane helices, and assign and model 14 supernumerary subunits. Thus, we significantly advance knowledge of the structure of mammalian complex I and the architecture of its supernumerary ensemble around the core domains. Our structure provides insights into the roles of the supernumerary subunits in regulation, assembly and homeostasis, and a basis for understanding the effects of mutations that cause a diverse range of human diseases. PMID:25209663

  4. Crossroads between Bacterial and Mammalian Glycosyltransferases

    PubMed Central

    Brockhausen, Inka

    2014-01-01

    Bacterial glycosyltransferases (GT) often synthesize the same glycan linkages as mammalian GT; yet, they usually have very little sequence identity. Nevertheless, enzymatic properties, folding, substrate specificities, and catalytic mechanisms of these enzyme proteins may have significant similarity. Thus, bacterial GT can be utilized for the enzymatic synthesis of both bacterial and mammalian types of complex glycan structures. A comparison is made here between mammalian and bacterial enzymes that synthesize epitopes found in mammalian glycoproteins, and those found in the O antigens of Gram-negative bacteria. These epitopes include Thomsen–Friedenreich (TF or T) antigen, blood group O, A, and B, type 1 and 2 chains, Lewis antigens, sialylated and fucosylated structures, and polysialic acids. Many different approaches can be taken to investigate the substrate binding and catalytic mechanisms of GT, including crystal structure analyses, mutations, comparison of amino acid sequences, NMR, and mass spectrometry. Knowledge of the protein structures and functions helps to design GT for specific glycan synthesis and to develop inhibitors. The goals are to develop new strategies to reduce bacterial virulence and to synthesize vaccines and other biologically active glycan structures. PMID:25368613

  5. A promoter-level mammalian expression atlas

    PubMed Central

    2015-01-01

    Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research. PMID:24670764

  6. Isolation of genomic DNA from mammalian cells.

    PubMed

    Koh, Cheryl M

    2013-01-01

    The isolation of genomic DNA from mammalian cells is a routine molecular biology laboratory technique with numerous downstream applications. The isolated DNA can be used as a template for PCR, cloning, and genotyping and to generate genomic DNA libraries. It can also be used for sequencing to detect mutations and other alterations, and for DNA methylation analyses. PMID:24011044

  7. [Placental developmental defects in cloned mammalian animals].

    PubMed

    Ao, Zheng; Liu, Dewu; Cai, Gengyuan; Wu, Zhenfang; Li, Zicong

    2016-05-01

    The cloning technique, also called somatic cell nuclear transfer (SCNT), has been successfully established and gradually applied to various mammalian species. However, the developmental rate of SCNT mammalian embryos is very low, usually at 1% to 5%, which limits the application of SCNT. Placental developmental defects are considered as the main cause of SCNT embryo development inhibition. Almost all of SCNT-derived mammalian placentas exhibit various abnormalities, such as placental hyperplasia, vascular defects and umbilical cord malformation. Mechanistically, these abnormalities result from failure of establishment of correct epigenetic modification in the trophectoderm genome, which leads to erroneous expression of important genes for placenta development-related, particularly imprinted genes. Consequently, aberrant imprinted gene expression gives rise to placental morphologic abnormalities and functional defects, therefore decreases developmental competence of cloned embryos. Currently, although numerous methods that can improve the developmental ability of SCNT-derived embryos have been reported, most of them are unable to substantially enhance the success rate of SCNT due to failure to eliminate the placental development defects. In this review, we summarize placental abnormalities and imprinted gene expression in mammalian cloning, and propose directions for the future research aiming to improve the cloning efficiency. PMID:27232488

  8. MAMMALIAN CELL MUTAGENESIS, BANBURY CONFERENCE (JOURNAL VERSION)

    EPA Science Inventory

    A conference on mammalian cell mutagenesis was held at the Banbury Center, Cold Spring Harbor, NY, USA, March 22-25, 1987. The objective of the conference was to provide a forum for discussions concerning the genetic, biochemical, and molecular basis of induced mutations in stand...

  9. Structure of mammalian respiratory complex I.

    PubMed

    Zhu, Jiapeng; Vinothkumar, Kutti R; Hirst, Judy

    2016-08-18

    Complex I (NADH:ubiquinone oxidoreductase), one of the largest membrane-bound enzymes in the cell, powers ATP synthesis in mammalian mitochondria by using the reducing potential of NADH to drive protons across the inner mitochondrial membrane. Mammalian complex I (ref. 1) contains 45 subunits, comprising 14 core subunits that house the catalytic machinery (and are conserved from bacteria to humans) and a mammalian-specific cohort of 31 supernumerary subunits. Knowledge of the structures and functions of the supernumerary subunits is fragmentary. Here we describe a 4.2-Å resolution single-particle electron cryomicroscopy structure of complex I from Bos taurus. We have located and modelled all 45 subunits, including the 31 supernumerary subunits, to provide the entire structure of the mammalian complex. Computational sorting of the particles identified different structural classes, related by subtle domain movements, which reveal conformationally dynamic regions and match biochemical descriptions of the 'active-to-de-active' enzyme transition that occurs during hypoxia. Our structures therefore provide a foundation for understanding complex I assembly and the effects of mutations that cause clinically relevant complex I dysfunctions, give insights into the structural and functional roles of the supernumerary subunits and reveal new information on the mechanism and regulation of catalysis. PMID:27509854

  10. Erythropoietin binding protein from mammalian serum

    DOEpatents

    Clemons, G.K.

    1997-04-29

    Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described. 11 figs.

  11. Erythropoietin binding protein from mammalian serum

    DOEpatents

    Clemons, Gisela K.

    1997-01-01

    Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described.

  12. Cold shock response in mammalian cells.

    PubMed

    Fujita, J

    1999-11-01

    Compared to bacteria and plants, the cold shock response has attracted little attention in mammals except in some areas such as adaptive thermogenesis, cold tolerance, storage of cells and organs, and recently, treatment of brain damage and protein production. At the cellular level, some responses of mammalian cells are similar to microorganisms; cold stress changes the lipid composition of cellular membranes, and suppresses the rate of protein synthesis and cell proliferation. Although previous studies have mostly dealt with temperatures below 20 degrees C, mild hypothermia (32 degrees C) can change the cell's response to subsequent stresses as exemplified by APG-1, a member of the HSP110 family. Furthermore, 32 degrees C induces expression of CIRP (cold-inducible RNA-binding protein), the first cold shock protein identified in mammalian cells, without recovery at 37 degrees C. Remniscent of HSP, CIRP is also expressed at 37 degrees C and developmentary regulated, possibly working as an RNA chaperone. Mammalian cells are metabolically active at 32 degrees C, and cells may survive and respond to stresses with different strategies from those at 37 degrees C. Cellular and molecular biology of mammalian cells at 32 degrees C is a new area expected to have considerable implications for medical sciences and possibly biotechnology. PMID:10943555

  13. AMMONIA REMOVAL FROM MAMMALIAN CELL CULTURE MEDIUM

    EPA Science Inventory

    Metabolites such as ammonia and lactic formed during mammalian cell culture can frequently be toxic to the cells themselves beyond a threshold concentration of the metabolites. ell culture conducted in the presence of such accumulated metabolites is therefore limited in productiv...

  14. Medical and experimental mammalian genetics: A perspective

    SciTech Connect

    McKusick, V.A.; Roderick, T.H.; Mori, J.; Paul, N.W.

    1987-01-01

    This book contains 14 papers. Some of the titles are: Structure and Organization of Mammalian Chromosomes: Normal and Abnormal; Globin Gene Structure and the Nature of Mutation; Retroviral DNA Content of the Mouse Genome; Maternal Genes: Mitochondrial Diseases; Human Evolution; and Prospects for Gene Replacement Therapy.

  15. Ticks Take Cues from Mammalian Interferon.

    PubMed

    de Silva, Aravinda M

    2016-07-13

    Interferons are considered a first line of immune defense restricted to vertebrates. In this issue of Cell Host & Microbe, Smith et al. (2016) demonstrate that mammalian interferon γ activates an antimicrobial response within ticks feeding on blood. The study suggests that arthropods have a parallel interferon-like defense system. PMID:27414493

  16. Genomics in mammalian cell culture bioprocessing

    PubMed Central

    Wuest, Diane M.; Harcum, Sarah W.; Lee, Kelvin H.

    2013-01-01

    Explicitly identifying the genome of a host organism including sequencing, mapping, and annotating its genetic code has become a priority in the field of biotechnology with aims at improving the efficiency and understanding of cell culture bioprocessing. Recombinant protein therapeutics, primarily produced in mammalian cells, constitute a $108 billion global market. The most common mammalian cell line used in biologic production processes is the Chinese hamster ovary (CHO) cell line, and although great improvements have been made in titer production over the past 25 years, the underlying molecular and physiological factors are not well understood. Confident understanding of CHO bioprocessing elements (e.g. cell line selection, protein production, and reproducibility of process performance and product specifications) would significantly improve with a well understood genome. This review describes mammalian cell culture use in bioprocessing, the importance of obtaining CHO cell line genetic sequences, and the current status of sequencing efforts. Furthermore, transcriptomic techniques and gene expression tools are presented, and case studies exploring genomic techniques and applications aimed to improve mammalian bioprocess performance are reviewed. Finally, future implications of genomic advances are surmised. PMID:22079893

  17. Cultured normal mammalian tissue and process

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J. (Inventor); Prewett, Tacey L. (Inventor); Wolf, David A. (Inventor); Spaulding, Glenn F. (Inventor)

    1993-01-01

    Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural and blood tissue. The cells are grown in vitro under microgravity culture conditions and form three dimensional cell aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.

  18. Enhanced Neurite Growth from Mammalian Neurons in Three-Dimensional Salmon Fibrin Gels

    PubMed Central

    Ju, Yo-El; Janmey, Paul A.; McCormick, Margaret; Sawyer, Evelyn S.; Flanagan, Lisa A.

    2007-01-01

    Three-dimensional fibrin matrices have been used as cellular substrates in vitro and as bridging materials for central nervous system repair. Cells can be embedded within fibrin gels since the polymerization process is non-toxic, making fibrin an attractive scaffold for transplanted cells. Most studies have utilized fibrin prepared from human or bovine blood proteins. However, fish fibrin may be well suited for neuronal growth since fish undergo remarkable central nervous system regeneration and molecules implicated in this process are present in fibrin. We assessed the growth of mammalian central nervous system neurons in bovine, human, and salmon fibrin and found that salmon fibrin gels encouraged the greatest degree of neurite (dendrite and axon) growth and were the most resistant to degradation by cellular proteases. The neurite growth-promoting effect was not due to the thrombin used to polymerize the gels or to any copurifying plasminogen. Co-purified fibronectin partially accounted for the effect on neurites, and blockade of fibrinogen/fibrin-binding integrins markedly decreased neurite growth. Anion exchange chromatography revealed different elution profiles for salmon and mammalian fibrinogens. These data demonstrate that salmon fibrin encourages the growth of neurites from mammalian neurons and suggest that salmon fibrin may be a beneficial scaffold for neuronal regrowth after CNS injury. PMID:17258313

  19. Constructing the suprachiasmatic nucleus: a watchmaker's perspective on the central clockworks

    PubMed Central

    Bedont, Joseph L.; Blackshaw, Seth

    2015-01-01

    The circadian system constrains an organism's palette of behaviors to portions of the solar day appropriate to its ecological niche. The central light-entrained clock in the suprachiasmatic nucleus (SCN) of the mammalian circadian system has evolved a complex network of interdependent signaling mechanisms linking multiple distinct oscillators to serve this crucial function. However, studies of the mechanisms controlling SCN development have greatly lagged behind our understanding of its physiological functions. We review advances in the understanding of adult SCN function, what has been described about SCN development to date, and the potential of both current and future studies of SCN development to yield important insights into master clock function, dysfunction, and evolution. PMID:26005407

  20. NON-MAMMALIAN ESTROGENICITY SCREEN: RAINBOW TROUT ESTROGEN RECEPTOR BINDING

    EPA Science Inventory

    The U.S. EPA has been mandated to screen industrial chemicals and pesticides for potential endocrine activity. Current assays for measuring endocrine activity are primarily mammalian-based. The appropriateness of extrapolating mammalian results to non-mammalian species is uncert...

  1. Long-term tracing of the BrdU label-retaining cells in adult rat brain.

    PubMed

    Zhang, Lei; Li, Haihong; Zeng, Shaopeng; Chen, Lu; Fang, Zeman; Huang, Qingjun

    2015-03-30

    Stem cells have been shown to be label-retaining, slow-cycling cells. In the adult mammalian central nervous system, the distribution of the stem cells is inconsistent among previous studies. The purpose of the present study was to determine the distribution of BrdU-LRCs and the cell types of the BrdU-LRCs in rat brain. To label BrdU-LRCs in rat brain, six newborn rats were administered intraperitoneal injections of BrdU 50mg/kg/time twice a day at 2h intervals, over four consecutive days. The BrdU-LRCs were detected by immunohistochemistry, the cell types were examined by double immunofluorescence staining for BrdU/GFAP and BrdU/MAP2, and the percentage of BrdU-LRCs was calculated following a chase period of 24 weeks post-injection. We observed that BrdU-LRCs distributed extensively in rat brain. In the LV, DG, striatum, cerebellum and neocortex, the percentage of BrdU-LRCs was 11.3 ± 2.5%, 10.9 ± 1.3%, 6.4 ± 1.2%, 5.6 ± 0.8%, and 4.9 ± 0.6%, respectively. The highest density of BrdU-LRCs was in LV and DG, the known stem cell sites in adult mammalian brain. Both BrdU/GFAP and BrdU/MAP2 double-staining cells could be detected in the above five brain subregions. Ongoing cell production was widespread in the adult mammalian brain, which would allow us to reevaluate the capacity and potentiality of the brain in homeostasis, wound repair, and regeneration. PMID:25681624

  2. Problems of allometric scaling analysis: examples from mammalian reproductive biology.

    PubMed

    Martin, Robert D; Genoud, Michel; Hemelrijk, Charlotte K

    2005-05-01

    Biological scaling analyses employing the widely used bivariate allometric model are beset by at least four interacting problems: (1) choice of an appropriate best-fit line with due attention to the influence of outliers; (2) objective recognition of divergent subsets in the data (allometric grades); (3) potential restrictions on statistical independence resulting from phylogenetic inertia; and (4) the need for extreme caution in inferring causation from correlation. A new non-parametric line-fitting technique has been developed that eliminates requirements for normality of distribution, greatly reduces the influence of outliers and permits objective recognition of grade shifts in substantial datasets. This technique is applied in scaling analyses of mammalian gestation periods and of neonatal body mass in primates. These analyses feed into a re-examination, conducted with partial correlation analysis, of the maternal energy hypothesis relating to mammalian brain evolution, which suggests links between body size and brain size in neonates and adults, gestation period and basal metabolic rate. Much has been made of the potential problem of phylogenetic inertia as a confounding factor in scaling analyses. However, this problem may be less severe than suspected earlier because nested analyses of variance conducted on residual variation (rather than on raw values) reveals that there is considerable variance at low taxonomic levels. In fact, limited divergence in body size between closely related species is one of the prime examples of phylogenetic inertia. One common approach to eliminating perceived problems of phylogenetic inertia in allometric analyses has been calculation of 'independent contrast values'. It is demonstrated that the reasoning behind this approach is flawed in several ways. Calculation of contrast values for closely related species of similar body size is, in fact, highly questionable, particularly when there are major deviations from the best

  3. Inservice Instructors: Adult Educator Competencies.

    ERIC Educational Resources Information Center

    Petersen, Mary Beth Harper

    1983-01-01

    Describes how fourteen principles of adult education provide the conceptual framework for performance competencies to guide the daily practice of instructors in the centralized inservice department of a large acute-care hospital. (JOW)

  4. The Africa Madagascar connection and mammalian migrations

    NASA Astrophysics Data System (ADS)

    Rabinowitz, Philip D.; Woods, Stephen

    2006-03-01

    Madagascar separated from Africa in the Middle-Late Jurassic and has been in its present position relative to Africa since the Early Cretaceous (˜120-130 my). Several Early Eocene to Late Oligocene (˜50-26 my) terrestrial mammalian groups are observed on Madagascar that have a similar ancestral lineage to those found in Africa. These mammalian groups means of transport across the Mozambique Channel from Africa to Madagascar was either by traversing on exposed land masses across a land bridge or by swimming/rafting, since (1) Madagascar has been separated from mainland Africa for at least 70 my before their arrival, and (2) it is unlikely that similar ancestral lineage's evolved simultaneously in separated regions. No evidence has been found for a land bridge across the Mozambique Channel. The mammals thus either swam or have been swept away on vegetation mats from rivers flowing out of Mozambique or Tanzania.

  5. Mammalian Sperm Motility: Observation and Theory

    NASA Astrophysics Data System (ADS)

    Gaffney, E. A.; Gadêlha, H.; Smith, D. J.; Blake, J. R.; Kirkman-Brown, J. C.

    2011-01-01

    Mammalian spermatozoa motility is a subject of growing importance because of rising human infertility and the possibility of improving animal breeding. We highlight opportunities for fluid and continuum dynamics to provide novel insights concerning the mechanics of these specialized cells, especially during their remarkable journey to the egg. The biological structure of the motile sperm appendage, the flagellum, is described and placed in the context of the mechanics underlying the migration of mammalian sperm through the numerous environments of the female reproductive tract. This process demands certain specific changes to flagellar movement and motility for which further mechanical insight would be valuable, although this requires improved modeling capabilities, particularly to increase our understanding of sperm progression in vivo. We summarize current theoretical studies, highlighting the synergistic combination of imaging and theory in exploring sperm motility, and discuss the challenges for future observational and theoretical studies in understanding the underlying mechanics.

  6. Mammalian hairs in Early Cretaceous amber

    NASA Astrophysics Data System (ADS)

    Vullo, Romain; Girard, Vincent; Azar, Dany; Néraudeau, Didier

    2010-07-01

    Two mammalian hairs have been found in association with an empty puparium in a ˜100-million-year-old amber (Early Cretaceous) from France. Although hair is known to be an ancestral, ubiquitous feature in the crown Mammalia, the structure of Mesozoic hair has never been described. In contrast to fur and hair of some Jurassic and Cretaceous mammals preserved as carbonized filaments, the exceptional preservation of the fossils described here allows for the study of the cuticular structure. Results show the oldest direct evidence of hair with a modern scale pattern. This discovery implies that the morphology of hair cuticula may have remained unchanged throughout most of mammalian evolution. The association of these hairs with a possible fly puparium provides paleoecological information and indicates peculiar taphonomic conditions.

  7. Mammalian Sirtuins: Biological Insights and Disease Relevance

    PubMed Central

    Haigis, Marcia C.; Sinclair, David A.

    2010-01-01

    Aging is accompanied by a decline in the healthy function of multiple organ systems, leading to increased incidence and mortality from diseases such as type II diabetes mellitus, neurodegenerative diseases, cancer, and cardiovascular disease. Historically, researchers have focused on investigating individual pathways in isolated organs as a strategy to identify the root cause of a disease, with hopes of designing better drugs. Studies of aging in yeast led to the discovery of a family of conserved enzymes known as the sirtuins, which affect multiple pathways that increase the life span and the overall health of organisms. Since the discovery of the first known mammalian sirtuin, SIRT1, 10 years ago, there have been major advances in our understanding of the enzymology of sirtuins, their regulation, and their ability to broadly improve mammalian physiology and health span. This review summarizes and discusses the advances of the past decade and the challenges that will confront the field in the coming years. PMID:20078221

  8. Mammalian lipoxygenases and their biological relevance

    PubMed Central

    Kuhn, Hartmut; Banthiya, Swathi; van Leyen, Klaus

    2015-01-01

    Lipoxygenases (LOXs) form a heterogeneous class of lipid peroxidizing enzymes, which have been implicated in cell proliferation and differentiation but also in the pathogenesis of various diseases with major public health relevance. As other fatty acid dioxygenases LOX oxidize polyunsaturated fatty acids to their corresponding hydroperoxy derivatives, which are further transformed to bioactive lipid mediators (eicosanoids and related substances). On the other hand, lipoxygenases are key players in regulation of the cellular redox homeostasis, which is an important element in gene expression regulation. Although the first mammalian lipoxygenases were discovered 40 years ago and although the enzymes have been well characterized with respect to their structural and functional properties the biological roles of the different lipoxygenase isoforms are not completely understood. This review is aimed at summarizing the current knowledge on the physiological roles of different mammalian LOX-isoforms and their patho-physiological function in inflammatory, metabolic, hyperproliferative, neurodegenerative and infectious disorders. PMID:25316652

  9. Freezing mammalian cells for production of biopharmaceuticals.

    PubMed

    Seth, Gargi

    2012-03-01

    Cryopreservation techniques utilize very low temperatures to preserve the structure and function of living cells. Various strategies have been developed for freezing mammalian cells of biological and medical significance. This paper highlights the importance and application of cryopreservation for recombinant mammalian cells used in the biopharmaceutical industry to produce high-value protein therapeutics. It is a primer that aims to give insight into the basic principles of cell freezing for the benefit of biopharmaceutical researchers with limited or no prior experience in cryobiology. For the more familiar researchers, key cell banking parameters such as the cell density and hold conditions have been reviewed to possibly help optimize their specific cell freezing protocols. It is important to understand the mechanisms underlying the freezing of complex and sensitive cellular entities as we implement best practices around the techniques and strategies used for cryopreservation. PMID:22226818

  10. Structure and function of mammalian aldehyde oxidases.

    PubMed

    Terao, Mineko; Romão, Maria João; Leimkühler, Silke; Bolis, Marco; Fratelli, Maddalena; Coelho, Catarina; Santos-Silva, Teresa; Garattini, Enrico

    2016-04-01

    Mammalian aldehyde oxidases (AOXs; EC1.2.3.1) are a group of conserved proteins belonging to the family of molybdo-flavoenzymes along with the structurally related xanthine dehydrogenase enzyme. AOXs are characterized by broad substrate specificity, oxidizing not only aromatic and aliphatic aldehydes into the corresponding carboxylic acids, but also hydroxylating a series of heteroaromatic rings. The number of AOX isoenzymes expressed in different vertebrate species is variable. The two extremes are represented by humans, which express a single enzyme (AOX1) in many organs and mice or rats which are characterized by tissue-specific expression of four isoforms (AOX1, AOX2, AOX3, and AOX4). In vertebrates each AOX isoenzyme is the product of a distinct gene consisting of 35 highly conserved exons. The extant species-specific complement of AOX isoenzymes is the result of a complex evolutionary process consisting of a first phase characterized by a series of asynchronous gene duplications and a second phase where the pseudogenization and gene deletion events prevail. In the last few years remarkable advances in the elucidation of the structural characteristics and the catalytic mechanisms of mammalian AOXs have been made thanks to the successful crystallization of human AOX1 and mouse AOX3. Much less is known about the physiological function and physiological substrates of human AOX1 and other mammalian AOX isoenzymes, although the importance of these proteins in xenobiotic metabolism is fairly well established and their relevance in drug development is increasing. This review article provides an overview and a discussion of the current knowledge on mammalian AOX. PMID:26920149

  11. Mammalian Evolution May not Be Strictly Bifurcating

    PubMed Central

    Hallström, Björn M.; Janke, Axel

    2010-01-01

    The massive amount of genomic sequence data that is now available for analyzing evolutionary relationships among 31 placental mammals reduces the stochastic error in phylogenetic analyses to virtually zero. One would expect that this would make it possible to finally resolve controversial branches in the placental mammalian tree. We analyzed a 2,863,797 nucleotide-long alignment (3,364 genes) from 31 placental mammals for reconstructing their evolution. Most placental mammalian relationships were resolved, and a consensus of their evolution is emerging. However, certain branches remain difficult or virtually impossible to resolve. These branches are characterized by short divergence times in the order of 1–4 million years. Computer simulations based on parameters from the real data show that as little as about 12,500 amino acid sites could be sufficient to confidently resolve short branches as old as about 90 million years ago (Ma). Thus, the amount of sequence data should no longer be a limiting factor in resolving the relationships among placental mammals. The timing of the early radiation of placental mammals coincides with a period of climate warming some 100–80 Ma and with continental fragmentation. These global processes may have triggered the rapid diversification of placental mammals. However, the rapid radiations of certain mammalian groups complicate phylogenetic analyses, possibly due to incomplete lineage sorting and introgression. These speciation-related processes led to a mosaic genome and conflicting phylogenetic signals. Split network methods are ideal for visualizing these problematic branches and can therefore depict data conflict and possibly the true evolutionary history better than strictly bifurcating trees. Given the timing of tectonics, of placental mammalian divergences, and the fossil record, a Laurasian rather than Gondwanan origin of placental mammals seems the most parsimonious explanation. PMID:20591845

  12. A possible role for the immune system in adult neurogenesis: new insights from an invertebrate model.

    PubMed

    Harzsch, Steffen; von Bohlen Und Halbach, Oliver

    2016-04-01

    Persistent neurogenesis in the adult brain of both vertebrates and invertebrates was previously considered to be driven by self-renewing neuronal stem cells of ectodermal origin. Recent findings in an invertebrate model challenge this view and instead provide evidence for a recruitment of neuronal precursors from a non-neuronal source. In the brain of adult crayfish, a neurogenic niche was identified that contributes progeny to the adult central olfactory pathway. The niche may function in attracting cells from the hemolymph and transforming them into cells with a neuronal fate. This finding implies that the first-generation neuronal precursors located in the crayfish neurogenic niche are not self-renewing. Evidence is summarized in support of a critical re-evaluation of long-term self-renewal of mammalian neuronal stem cells. Latest findings suggest that a tight link between the immune system and the system driving adult neurogenesis may not only exist in the crayfish but also in mammals. PMID:26739123

  13. The response of the anterior striatum during adult human vocal learning

    PubMed Central

    Leech, Robert; Iverson, Paul; Wise, Richard J. S.

    2014-01-01

    Research on mammals predicts that the anterior striatum is a central component of human motor learning. However, because vocalizations in most mammals are innate, much of the neurobiology of human vocal learning has been inferred from studies on songbirds. Essential for song learning is a pathway, the homolog of mammalian cortical-basal ganglia “loops,” which includes the avian striatum. The present functional magnetic resonance imaging (fMRI) study investigated adult human vocal learning, a skill that persists throughout life, albeit imperfectly given that late-acquired languages are spoken with an accent. Monolingual adult participants were scanned while repeating novel non-native words. After training on the pronunciation of half the words for 1 wk, participants underwent a second scan. During scanning there was no external feedback on performance. Activity declined sharply in left and right anterior striatum, both within and between scanning sessions, and this change was independent of training and performance. This indicates that adult speakers rapidly adapt to the novel articulatory movements, possibly by using motor sequences from their native speech to approximate those required for the novel speech sounds. Improved accuracy correlated only with activity in motor-sensory perisylvian cortex. We propose that future studies on vocal learning, using different behavioral and pharmacological manipulations, will provide insights into adult striatal plasticity and its potential for modification in both educational and clinical contexts. PMID:24805076

  14. Mammalian cells contain a second nucleocytoplasmic hexosaminidase.

    PubMed

    Gutternigg, Martin; Rendić, Dubravko; Voglauer, Regina; Iskratsch, Thomas; Wilson, Iain B H

    2009-04-01

    Some thirty years ago, work on mammalian tissues suggested the presence of two cytosolic hexosaminidases in mammalian cells; one of these has been more recently characterized in a recombinant form and has an important role in cellular function due to its ability to cleave beta-N-acetylglucosamine residues from a variety of nuclear and cytoplasmic proteins. However, the molecular nature of the second cytosolic hexosaminidase, named hexosaminidase D, has remained obscure. In the present study, we molecularly characterize for the first time the human and murine recombinant forms of enzymes, encoded by HEXDC genes, which appear to correspond to hexosaminidase D in terms of substrate specificity, pH dependency and temperature stability. Furthermore, a Myc-tagged form of this novel hexosaminidase displays a nucleocytoplasmic localization. Transcripts of the corresponding gene are expressed in a number of murine tissues. On the basis of its sequence, this enzyme represents, along with the lysosomal hexosaminidase subunits encoded by the HEXA and HEXB genes, the third class 20 glycosidase to be identified from mammalian sources. PMID:19040401

  15. [Telomere Recombination in Normal Mammalian Cells].

    PubMed

    Zhdanova, N S; Rubtsov, N B

    2016-01-01

    Two mechanisms of telomere length maintenance are known to date. The first includes the use of a special enzymatic telomerase complex to solve the problems that arise during the replication of linear DNA in a normal diploid and part of tumor cells. Alternative lengthening of telomeres (ALT), which is based on the homologous recombination of telomere DNA, represents the second mechanism. Until recently, ALT was assumed to be expressed only in 15-20% of tumors lacking active telomerase and, together with telomerase reactivation represented one of two possibilities to overcome the replicative senescence observed in somatic mammalian cells due to aging or during cell culturing in vitro. Previously described sporadic cases of combinations of the two mechanisms of telomere length maintenance in several cell lines in vitro were attributed to the experimental design rather than to a real biological phenomenon, since active cellular division without active telomerase was considered to be the "gold standard" of ALT. The present review describes the morphological and functional reorganizations of mammalian telomeres observed with ALT activation, as well as recently observed,and well-documented cases of combinations between ALT-like and telomerase-dependent mechanisms in mammalian cells. The possible role of telomere recombination in telomerase-dependent cells is discussed. PMID:27183789

  16. Aneuploidy in mammalian somatic cells in vivo.

    PubMed

    Cimino, M C; Tice, R R; Liang, J C

    1986-01-01

    Aneuploidy is an important potential source of human disease and of reproductive failure. Nevertheless, the ability of chemical agents to induce aneuploidy has been investigated only sporadically in intact (whole-animal) mammalian systems. A search of the available literature from the EMCT Aneuploidy File (for years 1970-1983) provided 112 papers that dealt with aneuploidy in mammalian somatic cells in vivo. 59 of these papers did not meet minimal criteria for analysis and were rejected from subsequent review. Of the remaining 53 papers that dealt with aneuploidy induction by chemical agents in mammalian somatic cells in vivo, only 3 (6%) contained data that were considered to be supported conclusively by adequate study designs, execution, and reporting. These 3 papers dealt with 2 chemicals, one of which, mercury, was negative for aneuploidy induction in humans, and the other, pyrimethamine, was positive in an experimental rodent study. The majority of papers (94%) were considered inconclusive for a variety of reasons. The most common reasons for calling a study inconclusive were (a) combining data on hyperploidy with those on hypoploidy and/or polyploidy, (b) an inadequate or unspecified number of animals and/or cells per animal scored per treatment group, and (c) poor data presentation such that animal-to-animal variability could not be assessed. Suggestions for protocol development are made, and the future directions of research into aneuploidy induction are discussed. PMID:3941670

  17. Short latency compound action potentials from mammalian gravity receptor organs

    NASA Technical Reports Server (NTRS)

    Jones, T. A.; Jones, S. M.

    1999-01-01

    Gravity receptor function was characterized in four mammalian species using far-field vestibular evoked potentials (VsEPs). VsEPs are compound action potentials of the vestibular nerve and central relays that are elicited by linear acceleration ramps applied to the cranium. Rats, mice, guinea pigs, and gerbils were studied. In all species, response onset occurred within 1.5 ms of the stimulus onset. Responses persisted during intense (116 dBSPL) wide-band (50 to 50 inverted question mark omitted inverted question mark000 Hz) forward masking, whereas auditory responses to intense clicks (112 dBpeSPL) were eliminated under the same conditions. VsEPs remained after cochlear extirpation but were eliminated following bilateral labyrinthectomy. Responses included a series of positive and negative peaks that occurred within 8 ms of stimulus onset (range of means at +6 dBre: 1.0 g/ms: P1=908 to 1062 micros, N1=1342 to 1475 micros, P2=1632 to 1952 micros, N2=2038 to 2387 micros). Mean response amplitudes at +6 dBre: 1.0 g/ms ranged from 0.14 to 0.99 microV. VsEP input/output functions revealed latency slopes that varied across peaks and species ranging from -19 to -51 micros/dB. Amplitude-intensity slopes also varied ranging from 0.04 to 0.08 microV/dB for rats and mice. Latency values were comparable to those of birds although amplitudes were substantially smaller in mammals. VsEP threshold values were considerably higher in mammals compared to birds and ranged from -8.1 to -10.5 dBre 1.0 g/ms across species. These results support the hypothesis that mammalian gravity receptors are less sensitive to dynamic stimuli than are those of birds.

  18. Understanding Adult Education and Training.

    ERIC Educational Resources Information Center

    Foley, Griff, Ed.

    This book introduces readers to issues, debates and literatures related to a number of central areas of practice in adult education and training, especially in Australia. It is intended as a first attempt to define the field of adult education in Australia in an analytical and theoretical, as opposed to a theoretical and practical sense. Written…

  19. Genetics and Epigenetics in Adult Neurogenesis.

    PubMed

    Hsieh, Jenny; Zhao, Xinyu

    2016-01-01

    The cellular basis of adult neurogenesis is neural stem cells residing in restricted areas of the adult brain. These cells self-renew and are multipotent. The maintenance of "stemness" and commitment to differentiation are tightly controlled by intricate molecular networks. Epigenetic mechanisms, including chromatin remodeling, DNA methylation, and noncoding RNAs (ncRNAs), have profound regulatory roles in mammalian gene expression. Significant advances have been made regarding the dynamic roles of epigenetic modulation and function. It has become evident that epigenetic regulators are key players in neural-stem-cell self-renewal, fate specification, and final maturation of new neurons, therefore, adult neurogenesis. Altered epigenetic regulation can result in a number of neurological and neurodevelopmental disorders. Here, we review recent discoveries that advance our knowledge in epigenetic regulation of mammalian neural stem cells and neurogenesis. Insights from studies of epigenetic gene regulation in neurogenesis may lead to new therapies for the treatment of neurodevelopmental disorders. PMID:27143699

  20. Loss of CLPP alleviates mitochondrial cardiomyopathy without affecting the mammalian UPRmt.

    PubMed

    Seiferling, Dominic; Szczepanowska, Karolina; Becker, Christina; Senft, Katharina; Hermans, Steffen; Maiti, Priyanka; König, Tim; Kukat, Alexandra; Trifunovic, Aleksandra

    2016-07-01

    The mitochondrial matrix protease CLPP plays a central role in the activation of the mitochondrial unfolded protein response (UPR(mt)) in Caenorhabditis elegans Far less is known about mammalian UPR(mt) signaling, although similar roles were assumed for central players, including CLPP To better understand the mammalian UPR(mt) signaling, we deleted CLPP in hearts of DARS2-deficient animals that show robust induction of UPR(mt) due to strong dysregulation of mitochondrial translation. Remarkably, our results clearly show that mammalian CLPP is neither required for, nor it regulates the UPR(mt) in mammals. Surprisingly, we demonstrate that a strong mitochondrial cardiomyopathy and diminished respiration due to DARS2 deficiency can be alleviated by the loss of CLPP, leading to an increased de novo synthesis of individual OXPHOS subunits. These results question our current understanding of the UPR(mt) signaling in mammals, while introducing CLPP as a possible novel target for therapeutic intervention in mitochondrial diseases. PMID:27154400

  1. Immunolocalization of the mitogen-activated protein kinases p42MAPK and JNK1, and their regulatory kinases MEK1 and MEK4, in adult rat central nervous system.

    PubMed

    Flood, D G; Finn, J P; Walton, K M; Dionne, C A; Contreras, P C; Miller, M S; Bhat, R V

    1998-08-31

    Cell survival, death, and stress signals are transduced from the cell surface to the cytoplasm and nucleus via a cascade of phosphorylation events involving the mitogen-activated protein kinase (MAPK) family. We compared the distribution of p42 mitogen-activated protein kinase (p42MAPK) and its activator MAPK or ERK kinase (MEK1; involved in transduction of growth and differentiation signals), with c-Jun N-terminal kinase (JNK1) and its activator MEK4 (involved in transduction of stress and death signals) in the adult rat central nervous system. All four kinases were present in the cytoplasm, dendrites, and axons of neurons. The presence of p42MAPK and JNK1 in dendrites and axons, as well as in cell bodies, suggests a role for these kinases in phosphorylation and regulation of cytoplasmic targets. A high degree of correspondence was found between the regional distribution of MEK1 and p42MAPK. Immunostaining for MEK1 and p42MAPK was intense in olfactory structures, neocortex, hippocampus, striatum, midline, and interlaminar thalamic nuclei, hypothalamus, brainstem, Purkinje cells, and spinal cord. In addition to neurons, p42MAPK was also present in oligodendrocytes. Whereas MEK4 was ubiquitously distributed, JNK1 was more selective. Immunostaining for MEK4 and JNK1 was intense in the olfactory bulb, lower cortical layers, the cholinergic basal forebrain, most nuclei of the thalamus, medial habenula, and cranial motor nuclei. The distribution of MEK1 and p42MAPK proteins only partially overlapped with that of MEK4 and JNK1. This suggests that the growth/differentiation and death/stress pathways affected by these kinases may not necessarily act to counterbalance each other in response to extracellular stimuli. The differential distribution of these kinases may control the specificity of neuronal function to extracellular signals. PMID:9714150

  2. Steroid hydroxylations: A paradigm for cytochrome P450 catalyzed mammalian monooxygenation reactions

    SciTech Connect

    Estabrook, Ronald W. . E-mail: Ronald.estabrook@utsouthwestern.edu

    2005-12-09

    The present article reviews the history of research on the hydroxylation of steroid hormones as catalyzed by enzymes present in mammalian tissues. The report describes how studies of steroid hormone synthesis have played a central role in the discovery of the monooxygenase functions of the cytochrome P450s. Studies of steroid hydroxylation reactions can be credited with showing that: (a) the adrenal mitochondrial enzyme catalyzing the 11{beta}-hydroxylation of deoxycorticosterone was the first mammalian enzyme shown by O{sup 18} studies to be an oxygenase; (b) the adrenal microsomal enzyme catalyzing the 21-hydroxylation of steroids was the first mammalian enzyme to show experimentally the proposed 1:1:1 stoichiometry (substrate:oxygen:reduced pyridine nucleotide) of a monooxygenase reaction; (c) application of the photochemical action spectrum technique for reversal of carbon monoxide inhibition of the 21-hydroxylation of 17{alpha}-OH progesterone was the first demonstration that cytochrome P450 was an oxygenase; (d) spectrophotometric studies of the binding of 17{alpha}-OH progesterone to bovine adrenal microsomal P450 revealed the first step in the cyclic reaction scheme of P450, as it catalyzes the 'activation' of oxygen in a monooxygenase reaction; (e) purified adrenodoxin was shown to function as an electron transport component of the adrenal mitochondrial monooxygenase system required for the activity of the 11{beta}-hydroxylase reaction. Adrenodoxin was the first iron-sulfur protein isolated and purified from mammalian tissues and the first soluble protein identified as a reductase of a P450; (f) fractionation of adrenal mitochondrial P450 and incubation with adrenodoxin and a cytosolic (flavoprotein) fraction were the first demonstration of the reconstitution of a mammalian P450 monooxygenase reaction.

  3. Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis.

    PubMed

    Li, Xue; Oghi, Kenneth A; Zhang, Jie; Krones, Anna; Bush, Kevin T; Glass, Christopher K; Nigam, Sanjay K; Aggarwal, Aneel K; Maas, Richard; Rose, David W; Rosenfeld, Michael G

    2003-11-20

    The precise mechanistic relationship between gene activation and repression events is a central question in mammalian organogenesis, as exemplified by the evolutionarily conserved sine oculis (Six), eyes absent (Eya) and dachshund (Dach) network of genetically interacting proteins. Here, we report that Six1 is required for the development of murine kidney, muscle and inner ear, and that it exhibits synergistic genetic interactions with Eya factors. We demonstrate that the Eya family has a protein phosphatase function, and that its enzymatic activity is required for regulating genes encoding growth control and signalling molecules, modulating precursor cell proliferation. The phosphatase function of Eya switches the function of Six1-Dach from repression to activation, causing transcriptional activation through recruitment of co-activators. The gene-specific recruitment of a co-activator with intrinsic phosphatase activity provides a molecular mechanism for activation of specific gene targets, including those regulating precursor cell proliferation and survival in mammalian organogenesis. PMID:14628042

  4. Selection of filamentous fungi of the Beauveria genus able to metabolize quercetin like mammalian cells

    PubMed Central

    de M. B. Costa, Eula Maria; Pimenta, Fabiana Cristina; Luz, Wolf Christian; de Oliveira, Valéria

    2008-01-01

    Microbial biotransformations constitute an important alternative as models for drug metabolism study in mammalians and have been used for the industrial synthesis of chemicals with pharmaceutical purposes. Several microorganisms with unique biotransformation ability have been found by intensive screening and put in commercial applications. Ten isolates of Beauveria sp genus filamentous fungi, isolated from soil in the central Brazil, and Beauveria bassiana ATCC 7159 were evaluated for their capability of quercetin biotransformation. Biotransformation processes were carried out for 24 up to 96 hours and monitored by mass spectrometry analyses of the culture broth. All strains were able to metabolize quercetin, forming mammalian metabolites. The results were different from those presented by other microorganisms previously utilized, attrackting attention because of the great diversity of reactions. Methylated, sulphated, monoglucuronidated, and glucuronidated conjugated metabolites were simultaneously detected. PMID:24031237

  5. Evolution and functions of Oct4 homologs in non-mammalian vertebrates.

    PubMed

    Onichtchouk, Daria

    2016-06-01

    PouV class transcription factor Oct4/Pou5f1 is a central regulator of indefinite pluripotency in mammalian embryonic stem cells (ESCs) but also participates in cell lineage specification in mouse embryos and in differentiating cell cultures. The molecular basis for this versatility, which is shared between Oct4 and its non-mammalian homologs Pou5f1 and Pou5f3, is not yet completely understood. Here, I review the current understanding of the evolution of PouV class transcription factors and discuss equivalent and diverse roles of Oct4 homologs in pluripotency, differentiation, and cell behavior in different vertebrate embryos. This article is part of a Special Issue entitled: The Oct Transcription Factor Family, edited by Dr. Dean Tantin. PMID:27058398

  6. Retinal cross talk in the mammalian visual system.

    PubMed

    Tang, Xiaolan; Tzekov, Radouil; Passaglia, Christopher L

    2016-06-01

    The existence and functional relevance of efferent optic nerve fibers in mammals have long been debated. While anatomical evidence for cortico-retinal and retino-retinal projections is substantial, physiological evidence is lacking, as efferent fibers are few in number and are severed in studies of excised retinal tissue. Here we show that interocular connections contribute to retinal bioelectrical activity in adult mammals. Full-field flash electroretinograms (ERGs) were recorded from one or both eyes of Brown-Norway rats under dark-adapted (n = 16) and light-adapted (n = 11) conditions. Flashes were confined to each eye by an opaque tube that blocked stray light. Monocular flashes evoked a small (5-15 μV) signal in the nonilluminated eye, which was named "crossed ERG" (xERG). The xERG began under dark-adapted conditions with a positive (xP1) wave that peaked at 70-90 ms and ended with slower negative (xN1) and positive (xP2) waves from 200 to 400 ms. xN1 was absent under light-adapted conditions. Injection of tetrodotoxin in either eye (n = 15) eliminated the xERG. Intraocular pressure elevation of the illuminated eye (n = 6) had the same effect. The treatments also altered the ERG b-wave in both eyes, and the alterations correlated with xERG disappearance. Optic nerve stimulation (n = 3) elicited a biphasic compound action potential in the nonstimulated nerve with 10- to 13-ms latency, implying that the xERG comes from slow-conducting (W type) fibers. Monocular dye application (n = 7) confirmed the presence of retino-retinal ganglion cells in adult rats. We conclude that mammalian eyes communicate directly with each other via a handful of optic nerve fibers. The cross talk alters retinal activity in rats, and perhaps other animals. PMID:26984426

  7. Flow cytometric sexing of mammalian sperm.

    PubMed

    Garner, Duane L

    2006-03-15

    This review reexamines parameters needed for optimization of flow cytometric sexing mammalian sperm and updates the current status of sperm sexing for various species where this technology is currently being applied. Differences in DNA content have provided both a method to differentiate between these sex-determining gametes and a method to sort them that can be used for predetermining sex in mammals. Although the DNA content of all cells for each mammalian species is highly conserved, slight but measurable DNA content differences of sperm occur within species even among cattle breeds due to different sizes of Y-chromosomes. Most mammals produce flattened, oval-headed sperm that can be oriented within a sorter using hydrodynamic forces. Multiplying the percentage the difference in DNA content of the X- or Y-chromosome bearing sperm times the area of the flat profile of the sperm head gives a simple sorting index that suggests that bull and boar sperm are well suited for separation in a flow sorter. Successful sperm sexing of various species must take into account the relative susceptibilities of gametes to the stresses that occur during sexing. Sorting conditions must be optimized for each species to achieve acceptable sperm sexing efficiency, usually at 90% accuracy. In the commercial application of sperm sexing to cattle, fertility of sex-sorted bull sperm at 2 x 10(6)/dose remains at 70-80% of unsexed sperm at normal doses of 10 to 20 x 10(6) sperm. DNA content measurements have been used to identify the sex-chromosome bearing sperm populations with good accuracy in semen from at least 23 mammalian species, and normal-appearing offspring have been produced from sexed sperm of at least seven species. PMID:16242764

  8. Structure of transcribing mammalian RNA polymerase II.

    PubMed

    Bernecky, Carrie; Herzog, Franz; Baumeister, Wolfgang; Plitzko, Jürgen M; Cramer, Patrick

    2016-01-28

    RNA polymerase (Pol) II produces messenger RNA during transcription of protein-coding genes in all eukaryotic cells. The Pol II structure is known at high resolution from X-ray crystallography for two yeast species. Structural studies of mammalian Pol II, however, remain limited to low-resolution electron microscopy analysis of human Pol II and its complexes with various proteins. Here we report the 3.4 Å resolution cryo-electron microscopy structure of mammalian Pol II in the form of a transcribing complex comprising DNA template and RNA transcript. We use bovine Pol II, which is identical to the human enzyme except for seven amino-acid residues. The obtained atomic model closely resembles its yeast counterpart, but also reveals unknown features. Binding of nucleic acids to the polymerase involves 'induced fit' of the mobile Pol II clamp and active centre region. DNA downstream of the transcription bubble contacts a conserved 'TPSA motif' in the jaw domain of the Pol II subunit RPB5, an interaction that is apparently already established during transcription initiation. Upstream DNA emanates from the active centre cleft at an angle of approximately 105° with respect to downstream DNA. This position of upstream DNA allows for binding of the general transcription elongation factor DSIF (SPT4-SPT5) that we localize over the active centre cleft in a conserved position on the clamp domain of Pol II. Our results define the structure of mammalian Pol II in its functional state, indicate that previous crystallographic analysis of yeast Pol II is relevant for understanding gene transcription in all eukaryotes, and provide a starting point for a mechanistic analysis of human transcription. PMID:26789250

  9. Mammalian niche conservation through deep time.

    PubMed

    DeSantis, Larisa R G; Beavins Tracy, Rachel A; Koontz, Cassandra S; Roseberry, John C; Velasco, Matthew C

    2012-01-01

    Climate change alters species distributions, causing plants and animals to move north or to higher elevations with current warming. Bioclimatic models predict species distributions based on extant realized niches and assume niche conservation. Here, we evaluate if proxies for niches (i.e., range areas) are conserved at the family level through deep time, from the Eocene to the Pleistocene. We analyze the occurrence of all mammalian families in the continental USA, calculating range area, percent range area occupied, range area rank, and range polygon centroids during each epoch. Percent range area occupied significantly increases from the Oligocene to the Miocene and again from the Pliocene to the Pleistocene; however, mammalian families maintain statistical concordance between rank orders across time. Families with greater taxonomic diversity occupy a greater percent of available range area during each epoch and net changes in taxonomic diversity are significantly positively related to changes in percent range area occupied from the Eocene to the Pleistocene. Furthermore, gains and losses in generic and species diversity are remarkably consistent with ~2.3 species gained per generic increase. Centroids demonstrate southeastern shifts from the Eocene through the Pleistocene that may correspond to major environmental events and/or climate changes during the Cenozoic. These results demonstrate range conservation at the family level and support the idea that niche conservation at higher taxonomic levels operates over deep time and may be controlled by life history traits. Furthermore, families containing megafauna and/or terminal Pleistocene extinction victims do not incur significantly greater declines in range area rank than families containing only smaller taxa and/or only survivors, from the Pliocene to Pleistocene. Collectively, these data evince the resilience of families to climate and/or environmental change in deep time, the absence of terminal Pleistocene

  10. Modeling Transformations of Neurodevelopmental Sequences across Mammalian Species

    PubMed Central

    Workman, Alan D.; Charvet, Christine J.; Clancy, Barbara; Darlington, Richard B.

    2013-01-01

    A general model of neural development is derived to fit 18 mammalian species, including humans, macaques, several rodent species, and six metatherian (marsupial) mammals. The goal of this work is to describe heterochronic changes in brain evolution within its basic developmental allometry, and provide an empirical basis to recognize equivalent maturational states across animals. The empirical data generating the model comprises 271 developmental events, including measures of initial neurogenesis, axon extension, establishment, and refinement of connectivity, as well as later events such as myelin formation, growth of brain volume, and early behavioral milestones, to the third year of human postnatal life. The progress of neural events across species is sufficiently predictable that a single model can be used to predict the timing of all events in all species, with a correlation of modeled values to empirical data of 0.9929. Each species' rate of progress through the event scale, described by a regression equation predicting duration of development in days, is highly correlated with adult brain size. Neural heterochrony can be seen in selective delay of retinogenesis in the cat, associated with greater numbers of rods in its retina, and delay of corticogenesis in all species but rodents and the rabbit, associated with relatively larger cortices in species with delay. Unexpectedly, precocial mammals (those unusually mature at birth) delay the onset of first neurogenesis but then progress rapidly through remaining developmental events. PMID:23616543

  11. Control of mammalian germ cell entry into meiosis.

    PubMed

    Feng, Chun-Wei; Bowles, Josephine; Koopman, Peter

    2014-01-25

    Germ cells are unique in undergoing meiosis to generate oocytes and sperm. In mammals, meiosis onset is before birth in females, or at puberty in males, and recent studies have uncovered several regulatory steps involved in initiating meiosis in each sex. Evidence suggests that retinoic acid (RA) induces expression of the critical pre-meiosis gene Stra8 in germ cells of the fetal ovary, pubertal testis and adult testis. In the fetal testis, CYP26B1 degrades RA, while FGF9 further antagonises RA signalling to suppress meiosis. Failsafe mechanisms involving Nanos2 may further suppress meiosis in the fetal testis. Here, we draw together the growing knowledge relating to these meiotic control mechanisms, and present evidence that they are co-ordinately regulated and that additional factors remain to be identified. Understanding this regulatory network will illuminate not only how the foundations of mammalian reproduction are laid, but also how mis-regulation of these steps can result in infertility or germline tumours. PMID:24076097

  12. Effects of Tetrodotoxin on the Mammalian Cardiovascular System

    PubMed Central

    Zimmer, Thomas

    2010-01-01

    The human genome encodes nine functional voltage-gated Na+ channels. Three of them, namely Nav1.5, Nav1.8, and Nav1.9, are resistant to nanomolar concentrations of tetrodotoxin (TTX; IC50 ≥ 1 μM). The other isoforms, which are predominantly expressed in the skeletal muscle and nervous system, are highly sensitive to TTX (IC50 ~ 10 nM). During the last two decades, it has become evident that in addition to the major cardiac isoform Nav1.5, several of those TTX sensitive isoforms are expressed in the mammalian heart. Whereas immunohistochemical and electrophysiological methods demonstrated functional expression in various heart regions, the physiological importance of those isoforms for cardiac excitation in higher mammals is still debated. This review summarizes our knowledge on the systemic cardiovascular effects of TTX in animals and humans, with a special focus on cardiac excitation and performance at lower concentrations of this marine drug. Altogether, these data strongly suggest that TTX sensitive Na+ channels, detected more recently in various heart tissues, are not involved in excitation phenomena in the healthy adult heart of higher mammals. PMID:20411124

  13. Modeling transformations of neurodevelopmental sequences across mammalian species.

    PubMed

    Workman, Alan D; Charvet, Christine J; Clancy, Barbara; Darlington, Richard B; Finlay, Barbara L

    2013-04-24

    A general model of neural development is derived to fit 18 mammalian species, including humans, macaques, several rodent species, and six metatherian (marsupial) mammals. The goal of this work is to describe heterochronic changes in brain evolution within its basic developmental allometry, and provide an empirical basis to recognize equivalent maturational states across animals. The empirical data generating the model comprises 271 developmental events, including measures of initial neurogenesis, axon extension, establishment, and refinement of connectivity, as well as later events such as myelin formation, growth of brain volume, and early behavioral milestones, to the third year of human postnatal life. The progress of neural events across species is sufficiently predictable that a single model can be used to predict the timing of all events in all species, with a correlation of modeled values to empirical data of 0.9929. Each species' rate of progress through the event scale, described by a regression equation predicting duration of development in days, is highly correlated with adult brain size. Neural heterochrony can be seen in selective delay of retinogenesis in the cat, associated with greater numbers of rods in its retina, and delay of corticogenesis in all species but rodents and the rabbit, associated with relatively larger cortices in species with delay. Unexpectedly, precocial mammals (those unusually mature at birth) delay the onset of first neurogenesis but then progress rapidly through remaining developmental events. PMID:23616543

  14. Stochastic resonance in mammalian neuronal networks

    SciTech Connect

    Gluckman, B.J.; So, P.; Netoff, T.I.; Spano, M.L.; Schiff, S.J. |

    1998-09-01

    We present stochastic resonance observed in the dynamics of neuronal networks from mammalian brain. Both sinusoidal signals and random noise were superimposed into an applied electric field. As the amplitude of the noise component was increased, an optimization (increase then decrease) in the signal-to-noise ratio of the network response to the sinusoidal signal was observed. The relationship between the measures used to characterize the dynamics is discussed. Finally, a computational model of these neuronal networks that includes the neuronal interactions with the electric field is presented to illustrate the physics behind the essential features of the experiment. {copyright} {ital 1998 American Institute of Physics.}

  15. Site of Mammalian Sperm Acrosome Reaction.

    PubMed

    Hirohashi, Noritaka

    2016-01-01

    Until recently, no special attention has been paid to the question of the site of mammalian sperm acrosome reaction (AR) in the female reproductive tract. Because AR is an essential process that enables the spermatozoon to fertilize, it is generally believed that it occurs at a specific step during sperm-egg interaction. It is generally thought that "the site of action coincides with the site of commitment." Thus, understanding the roles of AR and acrosomal substances is needed to gain insight into the site of the sperm commitment to undergo AR. PMID:27194354

  16. Mammalian cell culture capacity for biopharmaceutical manufacturing.

    PubMed

    Ecker, Dawn M; Ransohoff, Thomas C

    2014-01-01

    : With worldwide sales of biopharmaceuticals increasing each year and continuing growth on the horizon, the manufacture of mammalian biopharmaceuticals has become a major global enterprise. We describe the current and future industry wide supply of manufacturing capacity with regard to capacity type, distribution, and geographic location. Bioreactor capacity and the use of single-use products for biomanufacturing are also profiled. An analysis of the use of this capacity is performed, including a discussion of current trends that will influence capacity growth, availability, and utilization in the coming years. PMID:23748352

  17. Mammalian Developmental Genetics in the Twentieth Century

    PubMed Central

    Artzt, Karen

    2012-01-01

    This Perspectives is a review of the breathtaking history of mammalian genetics in the past century and, in particular, of the ways in which genetic thinking has illuminated aspects of mouse development. To illustrate the power of that thinking, selected hypothesis-driven experiments and technical advances are discussed. Also included in this account are the beginnings of mouse genetics at the Bussey Institute, Columbia University, and The Jackson Laboratory and a retrospective discussion of one of the classic problems in developmental genetics, the T/t complex and its genetic enigmas. PMID:23212897

  18. Apoptotic processes during mammalian preimplantation development.

    PubMed

    Fabian, Dusan; Koppel, Juraj; Maddox-Hyttel, Poul

    2005-07-15

    The paper provides a review of the current state of knowledge on apoptosis during normal preimplantation development based on the literature and on the authors' own findings. Information is focused on the occurrence and the characteristics of spontaneous apoptotic processes. Reports concerning the chronology and the incidence of programmed cell death in mouse, cow, pig and human embryos in early preimplantation stages up to the blastocyst stage are summarized. In addition, specific attributes of the apoptotic process in mammalian preimplantation development are provided, including the description of both morphological and biochemical features of cell death. PMID:15955348

  19. Tension tests on mammalian collagen fibrils.

    PubMed

    Liu, Yehe; Ballarini, Roberto; Eppell, Steven J

    2016-02-01

    A brief overview of isolated collagen fibril mechanics testing is followed by presentation of the first results testing fibrils isolated from load-bearing mammalian tendons using a microelectromechanical systems platform. The in vitro modulus (326 ± 112 MPa) and fracture stress (71 ± 23 MPa) are shown to be lower than previously measured on fibrils extracted from sea cucumber dermis and tested with the same technique. Scanning electron microscope images show the fibrils can fail with a mechanism that involves circumferential rupture, whereas the core of the fibril stays at least partially intact. PMID:26855757

  20. Light-sheet imaging of mammalian development.

    PubMed

    de Medeiros, Gustavo; Balázs, Bálint; Hufnagel, Lars

    2016-07-01

    Tackling modern cell and developmental biology questions requires fast 3D imaging with sub-cellular resolution over extended periods of time. Fluorescence microscopy has emerged as a powerful tool to image biological samples with high spatial and temporal resolution with molecular specificity. In particular, the highly efficient illumination and detection scheme of light-sheet fluorescence microscopy is starting to revolutionize the way we can monitor cellular and developmental processes in vivo. Here we summarize the state-of-the art of light-sheet imaging with a focus on mammalian development - from instrumentation, mounting and sample handling to data processing. PMID:27288888

  1. Mammalian Gravity Receptors: Structure and Metabolism

    NASA Technical Reports Server (NTRS)

    Ross, M. D.

    1985-01-01

    Calcium metabolism in mammalian gravity receptors is examined. To accomplish this objective it is necessary to study both the mineral deposits of the receptors, the otoconia, and the sensory areas themselves, the saccular and utricular maculas. The main focus was to elucidate the natures of the organic and inorganic phases of the crystalline masses, first in rat otoconia but more recently in otoliths and otoconia of a comparative series of vertebrates. Some of the ultrastructural findings in rat maculas, however, have prompted a more thorough study of the organization of the hair cells and innervation patterns in graviceptors.

  2. Derivation of the mammalian skull vault

    PubMed Central

    MORRISS-KAY, GILLIAN M.

    2001-01-01

    This review describes the evolutionary history of the mammalian skull vault as a basis for understanding its complex structure. Current information on the developmental tissue origins of the skull vault bones (mesoderm and neural crest) is assessed for mammals and other tetrapods. This information is discussed in the context of evolutionary changes in the proportions of the skull vault bones at the sarcopterygian-tetrapod transition. The dual tissue origin of the skull vault is considered in relation to the molecular mechanisms underlying osteogenic cell proliferation and differentiation in the sutural growth centres and in the proportionate contributions of different sutures to skull growth. PMID:11523816

  3. Central line infections - hospitals

    MedlinePlus

    ... infection; CVC - infection; Central venous device - infection; Infection control - central line infection; Nosocomial infection - central line infection; Hospital acquired infection - central line infection; Patient safety - central ...

  4. Gravitational Study of the Central Nervous System

    NASA Technical Reports Server (NTRS)

    Horowitz, J. M.

    1983-01-01

    A series of experiments conducted at 1G are discussed with reference to the role of calcium ions in information processing by the central nervous system. A technique is described which allows thin sections of a mammalian hippocampus to be isolated while maintaining neural activity. Two experiments carried out in hypergravic fields are also addressed; one investigating altered stimulation in the auditory system, the other determining temperature regulation responses in hypergravic fields.

  5. Pleistocene paleoenvironmental reconstructions and mammalian evolution in South-East Asia: focus on fossil faunas from Thailand

    NASA Astrophysics Data System (ADS)

    Tougard, C.; Montuire, S.

    2006-01-01

    Mammalian faunal studies have provided various clues for a better reconstruction of hominid Quaternary paleoenvironments. In this work, two methods were used: (1) the cenogram method, based on a graphical representation of the mammalian community structure, and (2) the species richness of murine rodents to estimate climatic parameters. These methods were applied to Middle and Late Pleistocene mammalian faunas of South-East Asia, from South China to Indonesia. Special emphasis was laid on a fauna from north-east Thailand dated back to approximately 170,000 years (i.e. a glacial period). This Thai fauna seems characteristic of a slightly open forested environment intermediate between those of present-day central Myanmar and the northern part of South China. In the Thai fauna, the occurrence of both cool-loving mammalian taxa, currently living further north, and species of larger body size than their living counterparts, indicates cooler and probably drier climatic conditions than present-day climates in Thailand. These results are quite consistent with Middle Pleistocene palynological records from South China and eastern Java. From other less well-documented Pleistocene faunas, taken into account in this work, humid climatic conditions of interglacial periods were revealed from large mammalian taxa.

  6. Redox regulation of mammalian sperm capacitation

    PubMed Central

    O’Flaherty, Cristian

    2015-01-01

    Capacitation is a series of morphological and metabolic changes necessary for the spermatozoon to achieve fertilizing ability. One of the earlier happenings during mammalian sperm capacitation is the production of reactive oxygen species (ROS) that will trigger and regulate a series of events including protein phosphorylation, in a time-dependent fashion. The identity of the sperm oxidase responsible for the production of ROS involved in capacitation is still elusive, and several candidates are discussed in this review. Interestingly, ROS-induced ROS formation has been described during human sperm capacitation. Redox signaling during capacitation is associated with changes in thiol groups of proteins located on the plasma membrane and subcellular compartments of the spermatozoon. Both, oxidation of thiols forming disulfide bridges and the increase on thiol content are necessary to regulate different sperm proteins associated with capacitation. Reducing equivalents such as NADH and NADPH are necessary to support capacitation in many species including humans. Lactate dehydrogenase, glucose-6-phospohate dehydrogenase, and isocitrate dehydrogenase are responsible in supplying NAD (P) H for sperm capacitation. Peroxiredoxins (PRDXs) are newly described enzymes with antioxidant properties that can protect mammalian spermatozoa; however, they are also candidates for assuring the regulation of redox signaling required for sperm capacitation. The dysregulation of PRDXs and of enzymes needed for their reactivation such as thioredoxin/thioredoxin reductase system and glutathione-S-transferases impairs sperm motility, capacitation, and promotes DNA damage in spermatozoa leading to male infertility. PMID:25926608

  7. The Mammalian Ovary from Genesis to Revelation

    PubMed Central

    Edson, Mark A.; Nagaraja, Ankur K.; Matzuk, Martin M.

    2009-01-01

    Two major functions of the mammalian ovary are the production of germ cells (oocytes), which allow continuation of the species, and the generation of bioactive molecules, primarily steroids (mainly estrogens and progestins) and peptide growth factors, which are critical for ovarian function, regulation of the hypothalamic-pituitary-ovarian axis, and development of secondary sex characteristics. The female germline is created during embryogenesis when the precursors of primordial germ cells differentiate from somatic lineages of the embryo and take a unique route to reach the urogenital ridge. This undifferentiated gonad will differentiate along a female pathway, and the newly formed oocytes will proliferate and subsequently enter meiosis. At this point, the oocyte has two alternative fates: die, a common destiny of millions of oocytes, or be fertilized, a fate of at most approximately 100 oocytes, depending on the species. At every step from germline development and ovary formation to oogenesis and ovarian development and differentiation, there are coordinated interactions of hundreds of proteins and small RNAs. These studies have helped reproductive biologists to understand not only the normal functioning of the ovary but also the pathophysiology and genetics of diseases such as infertility and ovarian cancer. Over the last two decades, parallel progress has been made in the assisted reproductive technology clinic including better hormonal preparations, prenatal genetic testing, and optimal oocyte and embryo analysis and cryopreservation. Clearly, we have learned much about the mammalian ovary and manipulating its most important cargo, the oocyte, since the birth of Louise Brown over 30 yr ago. PMID:19776209

  8. Production of small RNAs by mammalian Dicer.

    PubMed

    Svobodova, Eliska; Kubikova, Jana; Svoboda, Petr

    2016-06-01

    MicroRNA (miRNA) and RNA interference (RNAi) pathways employ RNase III Dicer for the biogenesis of small RNAs guiding post-transcriptional repression. Requirements for Dicer activity differ in the two pathways. The biogenesis of miRNAs requires a single Dicer cleavage of a short hairpin precursor to produce a small RNA with a precisely defined sequence, while small RNAs in RNAi come from a processive cleavage of a long double-stranded RNA (dsRNA) into a pool of small RNAs with different sequences. While Dicer is generally conserved among eukaryotes, its substrate recognition, cleavage, and biological roles differ. In Metazoa, a single Dicer can function as a universal factor for RNAi and miRNA pathways or as a factor adapted specifically for one of the pathways. In this review, we focus on the structure, function, and evolution of mammalian Dicer. We discuss key structural features of Dicer and other factors defining Dicer substrate repertoire and biological functions in mammals in comparison with invertebrate models. The key for adaptation of Dicer for miRNA or RNAi pathways is the N-terminal helicase, a dynamically evolving Dicer domain. Its functionality differs between mammals and invertebrates: the mammalian Dicer is well adapted to produce miRNAs while its ability to support RNAi is limited. PMID:27048428

  9. Ballistic transfection of mammalian cells in vivo

    SciTech Connect

    Kolesnikov, V.A.; Zelenin, A.V.; Zelenina, I.A.

    1995-11-01

    The method of ballistic transfection initially proposed for genetic transformation of plants was used for animal cells in vitro and in situ. The method consists in bombarding the transfected cells with microparticles of heavy metals carrying foreign DNA. Penetrating the cell nucleus, the microparticles transport the introduced gene. Successful genetic transformation of the cultured mouse cells and fish embryos was realized, and this allowed the study of mammalian cells in situ. The performed studies allowed us to demonstrate expression of the reporter genes of chloramphenicol acetyltransferase, galactosidase, and neomycin phosphotransferase in the mouse liver, mammary gland and kidney explants, in the liver and cross-striated muscle of mouse and rat in situ, and in developing mouse embryos at the stages of two-cell embryo, morula, and blastocyst. All these genes were introduced by ballistic transfection. In the liver and cross-striated muscle the transgene activity was detected within two to three months after transfection. Thus, the ballistic introduction of the foreign genes in the cells in situ was demonstrated, and this opens possibilities for the use of this method in gene therapy. Methodical aspects of the bombarding and transfection are considered in detail, and the published data on transfection and genetic transformation of mammalian cells are discussed. 41 refs., 13 figs., 1 tab.

  10. An Adaptive Threshold in Mammalian Neocortical Evolution

    PubMed Central

    Kalinka, Alex T.; Tomancak, Pavel; Huttner, Wieland B.

    2014-01-01

    Expansion of the neocortex is a hallmark of human evolution. However, determining which adaptive mechanisms facilitated its expansion remains an open question. Here we show, using the gyrencephaly index (GI) and other physiological and life-history data for 102 mammalian species, that gyrencephaly is an ancestral mammalian trait. We find that variation in GI does not evolve linearly across species, but that mammals constitute two principal groups above and below a GI threshold value of 1.5, approximately equal to 109 neurons, which may be characterized by distinct constellations of physiological and life-history traits. By integrating data on neurogenic period, neuroepithelial founder pool size, cell-cycle length, progenitor-type abundances, and cortical neuron number into discrete mathematical models, we identify symmetric proliferative divisions of basal progenitors in the subventricular zone of the developing neocortex as evolutionarily necessary for generating a 14-fold increase in daily prenatal neuron production, traversal of the GI threshold, and thus establishment of two principal groups. We conclude that, despite considerable neuroanatomical differences, changes in the length of the neurogenic period alone, rather than any novel neurogenic progenitor lineage, are sufficient to explain differences in neuron number and neocortical size between species within the same principal group. PMID:25405475

  11. Ecology and evolution of mammalian biodiversity

    PubMed Central

    Jones, Kate E.; Safi, Kamran

    2011-01-01

    Mammals have incredible biological diversity, showing extreme flexibility in eco-morphology, physiology, life history and behaviour across their evolutionary history. Undoubtedly, mammals play an important role in ecosystems by providing essential services such as regulating insect populations, seed dispersal and pollination and act as indicators of general ecosystem health. However, the macroecological and macroevolutionary processes underpinning past and present biodiversity patterns are only beginning to be explored on a global scale. It is also particularly important, in the face of the global extinction crisis, to understand these processes in order to be able to use this knowledge to prevent future biodiversity loss and loss of ecosystem services. Unfortunately, efforts to understand mammalian biodiversity have been hampered by a lack of data. New data compilations on current species' distributions, ecologies and evolutionary histories now allow an integrated approach to understand this biodiversity. We review and synthesize these new studies, exploring the past and present ecology and evolution of mammalian biodiversity, and use these findings to speculate about the mammals of our future. PMID:21807728

  12. Catabolic flexibility of mammalian-associated lactobacilli

    PubMed Central

    2013-01-01

    Metabolic flexibility may be generally defined as “the capacity for the organism to adapt fuel oxidation to fuel availability”. The metabolic diversification strategies used by individual bacteria vary greatly from the use of novel or acquired enzymes to the use of plasmid-localised genes and transporters. In this review, we describe the ability of lactobacilli to utilise a variety of carbon sources from their current or new environments in order to grow and survive. The genus Lactobacillus now includes more than 150 species, many with adaptive capabilities, broad metabolic capacity and species/strain variance. They are therefore, an informative example of a cell factory capable of adapting to new niches with differing nutritional landscapes. Indeed, lactobacilli naturally colonise and grow in a wide variety of environmental niches which include the roots and foliage of plants, silage, various fermented foods and beverages, the human vagina and the mammalian gastrointestinal tract (GIT; including the mouth, stomach, small intestine and large intestine). Here we primarily describe the metabolic flexibility of some lactobacilli isolated from the mammalian gastrointestinal tract, and we also describe some of the food-associated species with a proven ability to adapt to the GIT. As examples this review concentrates on the following species - Lb. plantarum, Lb. acidophilus, Lb. ruminis, Lb. salivarius, Lb. reuteri and Lb. sakei, to highlight the diversity and inter-relationships between the catabolic nature of species within the genus. PMID:23680304

  13. Catabolic flexibility of mammalian-associated lactobacilli.

    PubMed

    O'Donnell, Michelle M; O'Toole, Paul W; Ross, Reynolds Paul

    2013-01-01

    Metabolic flexibility may be generally defined as "the capacity for the organism to adapt fuel oxidation to fuel availability". The metabolic diversification strategies used by individual bacteria vary greatly from the use of novel or acquired enzymes to the use of plasmid-localised genes and transporters. In this review, we describe the ability of lactobacilli to utilise a variety of carbon sources from their current or new environments in order to grow and survive. The genus Lactobacillus now includes more than 150 species, many with adaptive capabilities, broad metabolic capacity and species/strain variance. They are therefore, an informative example of a cell factory capable of adapting to new niches with differing nutritional landscapes. Indeed, lactobacilli naturally colonise and grow in a wide variety of environmental niches which include the roots and foliage of plants, silage, various fermented foods and beverages, the human vagina and the mammalian gastrointestinal tract (GIT; including the mouth, stomach, small intestine and large intestine). Here we primarily describe the metabolic flexibility of some lactobacilli isolated from the mammalian gastrointestinal tract, and we also describe some of the food-associated species with a proven ability to adapt to the GIT. As examples this review concentrates on the following species - Lb. plantarum, Lb. acidophilus, Lb. ruminis, Lb. salivarius, Lb. reuteri and Lb. sakei, to highlight the diversity and inter-relationships between the catabolic nature of species within the genus. PMID:23680304

  14. Ecological adaptation determines functional mammalian olfactory subgenomes

    PubMed Central

    Hayden, Sara; Bekaert, Michaël; Crider, Tess A.; Mariani, Stefano; Murphy, William J.; Teeling, Emma C.

    2010-01-01

    The ability to smell is governed by the largest gene family in mammalian genomes, the olfactory receptor (OR) genes. Although these genes are well annotated in the finished human and mouse genomes, we still do not understand which receptors bind specific odorants or how they fully function. Previous comparative studies have been taxonomically limited and mostly focused on the percentage of OR pseudogenes within species. No study has investigated the adaptive changes of functional OR gene families across phylogenetically and ecologically diverse mammals. To determine the extent to which OR gene repertoires have been influenced by habitat, sensory specialization, and other ecological traits, to better understand the functional importance of specific OR gene families and thus the odorants they bind, we compared the functional OR gene repertoires from 50 mammalian genomes. We amplified more than 2000 OR genes in aquatic, semi-aquatic, and flying mammals and coupled these data with 48,000 OR genes from mostly terrestrial mammals, extracted from genomic projects. Phylogenomic, Bayesian assignment, and principle component analyses partitioned species by ecotype (aquatic, semi-aquatic, terrestrial, flying) rather than phylogenetic relatedness, and identified OR families important for each habitat. Functional OR gene repertoires were reduced independently in the multiple origins of aquatic mammals and were significantly divergent in bats. We reject recent neutralist views of olfactory subgenome evolution and correlate specific OR gene families with physiological requirements, a preliminary step toward unraveling the relationship between specific odors and respective OR gene families. PMID:19952139

  15. Molecular targets to promote central nervous system regeneration.

    PubMed

    Ferraro, Gino B; Alabed, Yazan Z; Fournier, Alyson E

    2004-01-01

    Trauma in the adult mammalian central nervous system (CNS) results in devastating clinical consequences due to the failure of injured axons to spontaneously regenerate. This regenerative failure can be attributed to both a lack of positive cues and to the presence of inhibitory cues that actively prevent regeneration. Substantial progress has been made in elucidating the molecular identity of negative cues present at the CNS injury site following injury. In the past several years, multiple myelin-associated inhibitors including Nogo, Myelin-associated glycoprotein and Oligodendrocyte-myelin glycoprotein have been characterized. Furthermore a neuronal receptor complex and several intracellular substrates leading to outgrowth inhibition have been identified. Rapid progress has also been made in identifying the role of neurotrophins and other positive cues in promoting axonal regrowth. The most recent advances in our understanding of positive stimuli for axon regeneration come from transplantation studies at the CNS lesion site. A number of artificial substrates, tissues, and cells including fetal cells, neural stem cells, Schwann cells and olfactory-ensheathing cells have been tested in animal models of CNS injury. Based on our expanded knowledge of inhibitory influences and on the positive characteristics of various transplants, a number of interventions have been tested to promote recovery in models of CNS trauma. These advances represent the first steps in developing a viable therapy to promote axon regeneration following CNS trauma. PMID:16181067

  16. Microglia in central nervous system repair after injury.

    PubMed

    Jin, Xuemei; Yamashita, Toshihide

    2016-05-01

    Accumulating evidence suggests that immune cells perform crucial inflammation-related functions including clearing dead tissue and promoting wound healing. Thus, they provide a conducive environment for better neuronal regeneration and functional recovery after adult mammalian central nervous system (CNS) injury. However, activated immune cells can also induce secondary damage of intact tissue and inhibit post-injury CNS repair. The inflammation response is due to the microglial production of cytokines and chemokines for the recruitment of peripheral immune cell populations, such as monocytes, neutrophils, dendritic cells and T lymphocytes. Interestingly, microglia and T lymphocytes can be detected at the injured site in both the early and later stages after nerve injury, whereas other peripheral immune cells infiltrate the injured parenchyma of the brain and spinal cord only in the early post-injury phase, and subsequently disappear. This suggests that microglia and T cells may play crucial roles in the post-injury functional recovery of the CNS. In this review, we summarize the current studies on microglia that examined neuronal regeneration and the molecular signalling mechanisms in the injured CNS. Better understanding of the effects of microglia on neural regeneration will aid the development of therapy strategies to enhance CNS functional recovery after injury. PMID:26861995

  17. Central California Action Associates, Inc.

    ERIC Educational Resources Information Center

    Sortor, Maia, Comp.

    The overall goal of the Central California Action Associates Inc. (CCAA) program is to provide basic education and pre-vocational training so that migrant and seasonal adult farm workers will be able to upgrade their economic and social lives. Without increased educational attainment, the San Joaquin Valley farm workers face a grim future because…

  18. Mottled Mice and Non-Mammalian Models of Menkes Disease

    PubMed Central

    Lenartowicz, Małgorzata; Krzeptowski, Wojciech; Lipiński, Paweł; Grzmil, Paweł; Starzyński, Rafał; Pierzchała, Olga; Møller, Lisbeth Birk

    2015-01-01

    Menkes disease is a multi-systemic copper metabolism disorder caused by mutations in the X-linked ATP7A gene and characterized by progressive neurodegeneration and severe connective tissue defects. The ATP7A protein is a copper (Cu)-transporting ATPase expressed in all tissues and plays a critical role in the maintenance of copper homeostasis in cells of the whole body. ATP7A participates in copper absorption in the small intestine and in copper transport to the central nervous system (CNS) across the blood-brain-barrier (BBB) and blood–cerebrospinal fluid barrier (BCSFB). Cu is essential for synaptogenesis and axonal development. In cells, ATP7A participates in the incorporation of copper into Cu-dependent enzymes during the course of its maturation in the secretory pathway. There is a high degree of homology (>80%) between the human ATP7A and murine Atp7a genes. Mice with mutations in the Atp7a gene, called mottled mutants, are well-established and excellent models of Menkes disease. Mottled mutants closely recapitulate the Menkes phenotype and are invaluable for studying Cu-metabolism. They provide useful models for exploring and testing new forms of therapy in Menkes disease. Recently, non-mammalian models of Menkes disease, Drosophila melanogaster and Danio rerio mutants were used in experiments which would be technically difficult to carry out in mammals. PMID:26732058

  19. Understanding global patterns of mammalian functional and phylogenetic diversity

    PubMed Central

    Safi, Kamran; Cianciaruso, Marcus V.; Loyola, Rafael D.; Brito, Daniel; Armour-Marshall, Katrina; Diniz-Filho, José Alexandre F.

    2011-01-01

    Documenting and exploring the patterns of diversity of life on Earth has always been a central theme in biology. Species richness despite being the most commonly used measure of diversity in macroecological studies suffers from not considering the evolutionary and ecological differences among species. Phylogenetic diversity (PD) and functional diversity (FD) have been proposed as alternative measures to overcome this limitation. Although species richness, PD and FD are closely related, their relationships have never been investigated on a global scale. Comparing PD and FD with species richness corroborated the general assumptions of surrogacy of the different diversity measures. However, the analysis of the residual variance suggested that the mismatches between the diversity measures are influenced by environmental conditions. PD increased relative to species richness with increasing mean annual temperature, whereas FD decreased with decreasing seasonality relative to PD. We also show that the tropical areas are characterized by a FD deficit, a phenomenon, that suggests that in tropical areas more species can be packed into the ecological space. We discuss potential mechanisms that could have resulted in the gradient of spatial mismatch observed in the different biodiversity measures and draw parallels to local scale studies. We conclude that the use of multiple diversity measures on a global scale can help to elucidate the relative importance of historical and ecological processes shaping the present gradients in mammalian diversity. PMID:21807734

  20. Mammalian cadherins DCHS1-FAT4 affect functional cerebral architecture.

    PubMed

    Beste, Christian; Ocklenburg, Sebastian; von der Hagen, Maja; Di Donato, Nataliya

    2016-06-01

    Cortical development is a complex process where a multitude of factors, including cadherins, plays an important role and where disruptions are known to have far reaching effects in neural development and cortical patterning. Cadherins play a central role in structural left-right differentiation during brain and body development, but their effect on a functional level remains elusive. We addressed this question by examining functional cerebral asymmetries in a patient with Van Maldergem Syndrome (VMS) (MIM#601390), which is caused by mutations in DCHS1-FAT4 cadherins, using a dichotic listening task. Using neurophysiological (EEG) data, we show that when key regulators during mammalian cerebral cortical development are disrupted due to DCHS1-FAT4 mutations, functional cerebral asymmetries are stronger. Basic perceptual processing of biaurally presented auditory stimuli was unaffected. This suggests that the strength and emergence of functional cerebral asymmetries is a direct function of proliferation and differentiation of neuronal stem cells. Moreover, these results support the recent assumption that the molecular mechanisms establishing early left-right differentiation are an important factor in the ontogenesis of functional lateralization. PMID:25930014

  1. Mammalian viviparity: a complex niche in the evolution of genomic imprinting

    PubMed Central

    Keverne, E B

    2014-01-01

    Evolution of mammalian reproductive success has witnessed a strong dependence on maternal resources through placental in utero development. Genomic imprinting, which has an active role in mammalian viviparity, also reveals a biased role for matrilineal DNA in its regulation. The co-existence of three matrilineal generations as one (mother, foetus and post-meiotic oocytes) has provided a maternal niche for transgenerational co-adaptive selection pressures to operate. In utero foetal growth has required increased maternal feeding in advance of foetal energetic demands; the mammary glands are primed for milk production in advance of birth, while the maternal hypothalamus is hormonally primed by the foetal placenta for nest building and post-natal care. Such biological forward planning resulted from maternal–foetal co-adaptation facilitated by co-expression of the same imprinted allele in the developing hypothalamus and placenta. This co-expression is concurrent with the placenta interacting with the adult maternal hypothalamus thereby providing a transgenerational template on which selection pressures may operate ensuring optimal maternalism in this and the next generation. Invasive placentation has further required the maternal immune system to adapt and positively respond to the foetal allotype. Pivotal to these mammalian evolutionary developments, genomic imprinting emerged as a monoallelic gene dosage regulatory mechanism of tightly interconnected gene networks providing developmental genetic stability for in utero development. PMID:24569636

  2. Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes

    PubMed Central

    Zebrowski, David C; Vergarajauregui, Silvia; Wu, Chi-Chung; Piatkowski, Tanja; Becker, Robert; Leone, Marina; Hirth, Sofia; Ricciardi, Filomena; Falk, Nathalie; Giessl, Andreas; Just, Steffen; Braun, Thomas; Weidinger, Gilbert; Engel, Felix B

    2015-01-01

    Mammalian cardiomyocytes become post-mitotic shortly after birth. Understanding how this occurs is highly relevant to cardiac regenerative therapy. Yet, how cardiomyocytes achieve and maintain a post-mitotic state is unknown. Here, we show that cardiomyocyte centrosome integrity is lost shortly after birth. This is coupled with relocalization of various centrosome proteins to the nuclear envelope. Consequently, postnatal cardiomyocytes are unable to undergo ciliogenesis and the nuclear envelope adopts the function as cellular microtubule organizing center. Loss of centrosome integrity is associated with, and can promote, cardiomyocyte G0/G1 cell cycle arrest suggesting that centrosome disassembly is developmentally utilized to achieve the post-mitotic state in mammalian cardiomyocytes. Adult cardiomyocytes of zebrafish and newt, which are able to proliferate, maintain centrosome integrity. Collectively, our data provide a novel mechanism underlying the post-mitotic state of mammalian cardiomyocytes as well as a potential explanation for why zebrafish and newts, but not mammals, can regenerate their heart. DOI: http://dx.doi.org/10.7554/eLife.05563.001 PMID:26247711

  3. Genome size evolution: sizing mammalian genomes.

    PubMed

    Redi, C A; Capanna, E

    2012-01-01

    The study of genome size (GS) and its variation is so fascinating to the scientific community because it constitutes the link between the present-day analytical and molecular studies of the genome and the old trunk of the holistic and synthetic view of the genome. The GS of several taxa vary over a broad range and do not correlate with the complexity of the organisms (the C-value paradox). However, the biology of transposable elements has let us reach a satisfactory view of the molecular mechanisms that give rise to GS variation and novelties, providing a less perplexing view of the significance of the GS (C-enigma). The knowledge of the composition and structure of a genome is a pre-requisite for trying to understand the evolution of the main genome signature: its size. The radiation of mammals provides an approximately 180-million-year test case for theories of how GS evolves. It has been found from data-mining GS databases that GS is a useful cyto-taxonomical instrument at the level of orders/superorders, providing genomic signatures characterizing Monotremata, Marsupialia, Afrotheria, Xenarthra, Laurasiatheria, and Euarchontoglires. A hypothetical ancestral mammalian-like GS of 2.9-3.7 pg has been suggested. This value appears compatible with the average values calculated for the high systematic levels of the extant Monotremata (∼2.97 pg) and Marsupialia (∼4.07 pg), suggesting invasion of mobile DNA elements concurrently with the separation of the older clades of Afrotheria (∼5.5 pg) and Xenarthra (∼4.5 pg) with larger GS, leaving the Euarchontoglires (∼3.4 pg) and Laurasiatheria (∼2.8 pg) genomes with fewer transposable elements. However, the paucity of GS data (546 mammalian species sized from 5,488 living species) for species, genera, and families calls for caution. Considering that mammalian species may be vanished even before they are known, GS data are sorely needed to phenotype the effects brought about by their variation and to validate any

  4. Mammalian Herbivores Alter the Population Growth and Spatial Establishment of an Early-Establishing Grassland Species.

    PubMed

    Sullivan, Lauren L; Danielson, Brent J; Harpole, W Stanley

    2016-01-01

    Plant-herbivore interactions influence the establishment context of plant species, as herbivores alter the community context in which individual species establish, and the spatial relationship between individuals and their source population as plants invade. This relationship can be described using an establishment kernel, which takes into account movement through seed dispersal, and subsequent establishment of adults. Mammalian herbivores are hypothesized to influence plant population growth and establishment through a combination of consumption of seeds and seedlings, and movement of seeds. While the movement abilities of plants are well known, we have very few empirical mechanistic tests of how biotic factors like mammalian herbivores influence this spread potential. As herbivores of all sizes are abundant on the landscape, we asked the question, how do mammalian herbivores influence the population growth, spatial establishment, and the community establishment context of an early-recruiting native prairie legume, Chamaecrista fasciculata? We planted C. fasciculata in source populations within a four-acre tallgrass prairie restoration in plots with and without herbivores, and monitored its establishment with respect to distance from the source populations. We found that herbivores decreased population growth, and decreased the mean and range establishment distance. Additionally, C. fasciculata established more often without herbivores, and when surrounded by weedy, annual species. Our results provide insight into how the interactions between plants and herbivores can alter the spatial dynamics of developing plant communities, which is vital for colonization and range spread with fragmentation and climate change. Mammalian herbivores have the potential to both slow rates of establishment, but also determine the types of plant communities that surround invading species. Therefore, it is essential to consider the herbivore community when attempting to restore

  5. Mammalian Herbivores Alter the Population Growth and Spatial Establishment of an Early-Establishing Grassland Species

    PubMed Central

    Sullivan, Lauren L.; Danielson, Brent J.; Harpole, W. Stanley

    2016-01-01

    Plant-herbivore interactions influence the establishment context of plant species, as herbivores alter the community context in which individual species establish, and the spatial relationship between individuals and their source population as plants invade. This relationship can be described using an establishment kernel, which takes into account movement through seed dispersal, and subsequent establishment of adults. Mammalian herbivores are hypothesized to influence plant population growth and establishment through a combination of consumption of seeds and seedlings, and movement of seeds. While the movement abilities of plants are well known, we have very few empirical mechanistic tests of how biotic factors like mammalian herbivores influence this spread potential. As herbivores of all sizes are abundant on the landscape, we asked the question, how do mammalian herbivores influence the population growth, spatial establishment, and the community establishment context of an early-recruiting native prairie legume, Chamaecrista fasciculata? We planted C. fasciculata in source populations within a four-acre tallgrass prairie restoration in plots with and without herbivores, and monitored its establishment with respect to distance from the source populations. We found that herbivores decreased population growth, and decreased the mean and range establishment distance. Additionally, C. fasciculata established more often without herbivores, and when surrounded by weedy, annual species. Our results provide insight into how the interactions between plants and herbivores can alter the spatial dynamics of developing plant communities, which is vital for colonization and range spread with fragmentation and climate change. Mammalian herbivores have the potential to both slow rates of establishment, but also determine the types of plant communities that surround invading species. Therefore, it is essential to consider the herbivore community when attempting to restore

  6. Diving into the Ice Bucket Challenge: Intraparenchymal Hemorrhage and the Mammalian Diving Reflex.

    PubMed

    McKee, Kathleen; Nelson, Sarah; Batra, Ayush; Klein, Joshua P; Henderson, Galen V

    2015-07-01

    Triggered by facial exposure to cold water and apnea, the mammalian diving reflex consists of bradycardia and peripheral arteriolar vasoconstriction leading to an increase in central arterial pressure. It has been previously associated with ischemic stroke but not definitively with intracerebral hemorrhage. We present a case of intracerebral hemorrhage occurring in a woman with poorly controlled hypertension following her participation in the amyotrophic lateral sclerosis fund-raising "Ice Bucket Challenge," in which ice-cold water was poured on her head. We suspect that facial exposure to ice-cold water triggered the diving reflex, causing a hypertensive surge and ultimately the intracerebral hemorrhage. PMID:26288676

  7. Chemical analysis of individual mammalian cells

    SciTech Connect

    Tan, W.; Yeung, E.S.

    1994-12-31

    The extremely small size of mammalian cells creates an unusual challenge for the analytical chemist, both in terms of separation and detection. Under a microscope, it is possible to confirm the injection of individual cells such as erythrocyte into capillaries with 10-{mu}m i.d. by hydrostatic pressure. The ionic contents can then be separated by capillary electrophoresis after the cell lyses. Enzymes at the zeptomole level can be monitored by on-column fluorescence enzyme assay. On-column particle-counting immunoassay can be applied to a broad range of analytes (antigens), also at the zeptomole level. The authors report here the simultaneous determination of the amounts of glucose-6-phosphate dehydrogenase (G6PDH) and their activities in individual erythrocytes by using a combination of the two detection schemes. Insights into the degradation of proteins as a function of cell age can be derived.

  8. Crystal structure of mammalian acid sphingomyelinase.

    PubMed

    Gorelik, Alexei; Illes, Katalin; Heinz, Leonhard X; Superti-Furga, Giulio; Nagar, Bhushan

    2016-01-01

    Acid sphingomyelinase (ASMase, ASM, SMPD1) converts sphingomyelin into ceramide, modulating membrane properties and signal transduction. Inactivating mutations in ASMase cause Niemann-Pick disease, and its inhibition is also beneficial in models of depression and cancer. To gain a better understanding of this critical therapeutic target, we determined crystal structures of mammalian ASMase in various conformations. The catalytic domain adopts a calcineurin-like fold with two zinc ions and a hydrophobic track leading to the active site. Strikingly, the membrane interacting saposin domain assumes either a closed globular conformation independent from the catalytic domain, or an open conformation, which establishes an interface with the catalytic domain essential for activity. Structural mapping of Niemann-Pick mutations reveals that most of them likely destabilize the protein's fold. This study sheds light on the molecular mechanism of ASMase function, and provides a platform for the rational development of ASMase inhibitors and therapeutic use of recombinant ASMase. PMID:27435900

  9. Crystal structure of mammalian acid sphingomyelinase

    PubMed Central

    Gorelik, Alexei; Illes, Katalin; Heinz, Leonhard X.; Superti-Furga, Giulio; Nagar, Bhushan

    2016-01-01

    Acid sphingomyelinase (ASMase, ASM, SMPD1) converts sphingomyelin into ceramide, modulating membrane properties and signal transduction. Inactivating mutations in ASMase cause Niemann–Pick disease, and its inhibition is also beneficial in models of depression and cancer. To gain a better understanding of this critical therapeutic target, we determined crystal structures of mammalian ASMase in various conformations. The catalytic domain adopts a calcineurin-like fold with two zinc ions and a hydrophobic track leading to the active site. Strikingly, the membrane interacting saposin domain assumes either a closed globular conformation independent from the catalytic domain, or an open conformation, which establishes an interface with the catalytic domain essential for activity. Structural mapping of Niemann–Pick mutations reveals that most of them likely destabilize the protein's fold. This study sheds light on the molecular mechanism of ASMase function, and provides a platform for the rational development of ASMase inhibitors and therapeutic use of recombinant ASMase. PMID:27435900

  10. Hysteresis in a synthetic mammalian gene network.

    PubMed

    Kramer, Beat P; Fussenegger, Martin

    2005-07-01

    Bistable and hysteretic switches, enabling cells to adopt multiple internal expression states in response to a single external input signal, have a pivotal impact on biological systems, ranging from cell-fate decisions to cell-cycle control. We have designed a synthetic hysteretic mammalian transcription network. A positive feedback loop, consisting of a transgene and transactivator (TA) cotranscribed by TA's cognate promoter, is repressed by constitutive expression of a macrolide-dependent transcriptional silencer, whose activity is modulated by the macrolide antibiotic erythromycin. The antibiotic concentration, at which a quasi-discontinuous switch of transgene expression occurs, depends on the history of the synthetic transcription circuitry. If the network components are imbalanced, a graded rather than a quasi-discontinuous signal integration takes place. These findings are consistent with a mathematical model. Synthetic gene networks, which are able to emulate natural gene expression behavior, may foster progress in future gene therapy and tissue engineering initiatives. PMID:15972812

  11. Nomenclature for mammalian soluble glutathione transferases.

    PubMed

    Mannervik, Bengt; Board, Philip G; Hayes, John D; Listowsky, Irving; Pearson, William R

    2005-01-01

    The nomenclature for human soluble glutathione transferases (GSTs) is extended to include new members of the GST superfamily that have been discovered, sequenced, and shown to be expressed. The GST nomenclature is based on primary structure similarities and the division of GSTs into classes of more closely related sequences. The classes are designated by the names of the Greek letters: Alpha, Mu, Pi, etc., abbreviated in Roman capitals: A, M, P, and so on. (The Greek characters should not be used.) Class members are distinguished by Arabic numerals and the native dimeric protein structures are named according to their subunit composition (e.g., GST A1-2 is the enzyme composed of subunits 1 and 2 in the Alpha class). Soluble GSTs from other mammalian species can be classified in the same manner as the human enzymes, and this chapter presents the application of the nomenclature to the rat and mouse GSTs. PMID:16399376

  12. Trapping mammalian protein complexes in viral particles

    PubMed Central

    Eyckerman, Sven; Titeca, Kevin; Van Quickelberghe, Emmy; Cloots, Eva; Verhee, Annick; Samyn, Noortje; De Ceuninck, Leentje; Timmerman, Evy; De Sutter, Delphine; Lievens, Sam; Van Calenbergh, Serge; Gevaert, Kris; Tavernier, Jan

    2016-01-01

    Cell lysis is an inevitable step in classical mass spectrometry–based strategies to analyse protein complexes. Complementary lysis conditions, in situ cross-linking strategies and proximal labelling techniques are currently used to reduce lysis effects on the protein complex. We have developed Virotrap, a viral particle sorting approach that obviates the need for cell homogenization and preserves the protein complexes during purification. By fusing a bait protein to the HIV-1 GAG protein, we show that interaction partners become trapped within virus-like particles (VLPs) that bud from mammalian cells. Using an efficient VLP enrichment protocol, Virotrap allows the detection of known binary interactions and MS-based identification of novel protein partners as well. In addition, we show the identification of stimulus-dependent interactions and demonstrate trapping of protein partners for small molecules. Virotrap constitutes an elegant complementary approach to the arsenal of methods to study protein complexes. PMID:27122307

  13. Fundamentals of Expression in Mammalian Cells.

    PubMed

    Dyson, Michael R

    2016-01-01

    Expression of proteins in mammalian cells is a key technology important for many functional studies on human and higher eukaryotic genes. Studies include the mapping of protein interactions, solving protein structure by crystallization and X-ray diffraction or solution phase NMR and the generation of antibodies to enable a range of studies to be performed including protein detection in vivo. In addition the production of therapeutic proteins and antibodies, now a multi billion dollar industry, has driven major advances in cell line engineering for the production of grams per liter of active proteins and antibodies. Here the key factors that need to be considered for successful expression in HEK293 and CHO cells are reviewed including host cells, expression vector design, transient transfection methods, stable cell line generation and cultivation conditions. PMID:27165328

  14. Mammalian telomeres and their partnership with lamins

    PubMed Central

    Burla, Romina; La Torre, Mattia; Saggio, Isabella

    2016-01-01

    ABSTRACT Chromosome ends are complex structures, which require a panel of factors for their elongation, replication, and protection. We describe here the mechanics of mammalian telomeres, dynamics and maintainance in relation to lamins. Multiple biochemical connections, including association of telomeres to the nuclear envelope and matrix, of telomeric proteins to lamins, and of lamin-associated proteins to chromosome ends, underline the interplay between lamins and telomeres. Paths toward senescence, such as defective telomere replication, altered heterochromatin organization, and impaired DNA repair, are common to lamins' and telomeres' dysfunction. The convergence of phenotypes can be interpreted through a model of dynamic, lamin-controlled functional platforms dedicated to the function of telomeres as fragile sites. The features of telomeropathies and laminopathies, and of animal models underline further overlapping aspects, including the alteration of stem cell compartments. We expect that future studies of basic biology and on aging will benefit from the analysis of this telomere-lamina interplay. PMID:27116558

  15. New consensus nomenclature for mammalian keratins

    PubMed Central

    Schweizer, Jürgen; Bowden, Paul E.; Coulombe, Pierre A.; Langbein, Lutz; Lane, E. Birgitte; Magin, Thomas M.; Maltais, Lois; Omary, M. Bishr; Parry, David A.D.; Rogers, Michael A.; Wright, Mathew W.

    2006-01-01

    Keratins are intermediate filament–forming proteins that provide mechanical support and fulfill a variety of additional functions in epithelial cells. In 1982, a nomenclature was devised to name the keratin proteins that were known at that point. The systematic sequencing of the human genome in recent years uncovered the existence of several novel keratin genes and their encoded proteins. Their naming could not be adequately handled in the context of the original system. We propose a new consensus nomenclature for keratin genes and proteins that relies upon and extends the 1982 system and adheres to the guidelines issued by the Human and Mouse Genome Nomenclature Committees. This revised nomenclature accommodates functional genes and pseudogenes, and although designed specifically for the full complement of human keratins, it offers the flexibility needed to incorporate additional keratins from other mammalian species. PMID:16831889

  16. Cenozoic climate change influences mammalian evolutionary dynamics

    PubMed Central

    Figueirido, Borja; Janis, Christine M.; Pérez-Claros, Juan A.; De Renzi, Miquel; Palmqvist, Paul

    2012-01-01

    Global climate change is having profound impacts on the natural world. However, climate influence on faunal dynamics at macroevolutionary scales remains poorly understood. In this paper we investigate the influence of climate over deep time on the diversity patterns of Cenozoic North American mammals. We use factor analysis to identify temporally correlated assemblages of taxa, or major evolutionary faunas that we can then study in relation to climatic change over the past 65 million years. These taxa can be grouped into six consecutive faunal associations that show some correspondence with the qualitative mammalian chronofaunas of previous workers. We also show that the diversity pattern of most of these chronofaunas can be correlated with the stacked deep-sea benthic foraminiferal oxygen isotope (δ18O) curve, which strongly suggests climatic forcing of faunal dynamics over a large macroevolutionary timescale. This study demonstrates the profound influence of climate on the diversity patterns of North American terrestrial mammals over the Cenozoic. PMID:22203974

  17. Voltage-gated sodium channels in the mammalian heart

    PubMed Central

    Zimmer, Thomas; Haufe, Volker; Blechschmidt, Steve

    2014-01-01

    Mammalian species express nine functional voltage-gated Na+ channels. Three of them, the cardiac-specific isoform Nav1.5 and the neuronal isoforms Nav1.8 and Nav1.9, are relatively resistant to the neurotoxin tetrodotoxin (TTX; IC50 ≥ 1 μM). The other six isoforms are highly sensitive to TTX with IC50 values in the nanomolar range. These isoforms are expressed in the central nervous system (Nav1.1, Nav1.2, Nav1.3, Nav1.6), in the skeletal muscle (Nav1.4), and in the peripheral nervous system (Nav1.6, Nav1.7). The isoform Nav1.5, encoded by the SCN5A gene, is responsible for the upstroke of the action potential in the heart. Mutations in SCN5A are associated with a variety of life-threatening arrhythmias, like long QT syndrome type 3 (LQT3), Brugada syndrome (BrS) or cardiac conduction disease (CCD). Previous immunohistochemical and electrophysiological assays demonstrated the cardiac expression of neuronal and skeletal muscle Na+ channels in the heart of various mammals, which led to far-reaching speculations on their function. However, when comparing the Na+ channel mRNA patterns in the heart of various mammalian species, only minute quantities of transcripts for TTX-sensitive Na+ channels were detectable in whole pig and human hearts, suggesting that these channels are not involved in cardiac excitation phenomena in higher mammals. This conclusion is strongly supported by the fact that mutations in TTX-sensitive Na+ channels were associated with epilepsy or skeletal muscle diseases, rather than with a pathological cardiac phenotype. Moreover, previous data from TTX-intoxicated animals and from cases of human tetrodotoxication showed that low TTX dosages caused at most little alterations of both the cardiac output and the electrocardiogram. Recently, genome-wide association studies identified SCN10A, the gene encoding Nav1.8, as a determinant of cardiac conduction parameters, and mutations in SCN10A have been associated with BrS. These novel findings opened a

  18. Adult Compacts.

    ERIC Educational Resources Information Center

    Further Education Unit, London (England).

    This bulletin focuses on adult compacts, three-way agreements among employers, potential employees, and trainers to provide the right kind of quality training to meet the employers' requirements. Part 1 is an executive summary of a report of the Adult Compacts Project, which studied three adult compacts in Birmingham and Loughborough, England, and…

  19. Signal transduction in mammalian oocytes during fertilization.

    PubMed

    Machaty, Zoltan

    2016-01-01

    Mammalian embryo development begins when the fertilizing sperm triggers a series of elevations in the oocyte's intracellular free Ca(2+) concentration. The elevations are the result of repeated release and re-uptake of Ca(2+) stored in the smooth endoplasmic reticulum. Ca(2+) release is primarily mediated by the phosphoinositide signaling system of the oocyte. The system is stimulated when the sperm causes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG); IP3 then binds its receptor on the surface of the endoplasmic reticulum that induces Ca(2+) release. The manner in which the sperm generates IP3, the Ca(2+) mobilizing second messenger, has been the subject of extensive research for a long time. The sperm factor hypothesis has eventually gained general acceptance, according to which it is a molecule from the sperm that diffuses into the ooplasm and stimulates the phosphoinositide cascade. Much evidence now indicates that the sperm-derived factor is phospholipase C-zeta (PLCζ) that cleaves PIP2 and generates IP3, eventually leading to oocyte activation. A recent addition to the candidate sperm factor list is the post-acrosomal sheath WW domain-binding protein (PAWP), whose role at fertilization is currently under debate. Ca(2+) influx across the plasma membrane is also important as, in the absence of extracellular Ca(2+), the oscillations run down prematurely. In pig oocytes, the influx that sustains the oscillations seems to be regulated by the filling status of the stores, whereas in the mouse other mechanisms might be involved. This work summarizes the current understanding of Ca(2+) signaling in mammalian oocytes. PMID:26453398

  20. Roles for learning in mammalian chemosensory responses.

    PubMed

    Griffiths, Philip R; Brennan, Peter A

    2015-02-01

    This article is part of a Special Issue "Chemosignals and Reproduction". A rich variety of chemosignals have been identified that influence mammalian behaviour, including peptides, proteins and volatiles. Many of these elicit innate effects acting either as pheromones within species or allelochemicals between species. However, even innate pheromonal responses in mammals are not as hard-wired as the original definition of the term would suggest. Many, if not most mammalian pheromonal responses are only elicited in certain behavioural or physiological contexts. Furthermore, certain pheromones are themselves rewarding and act as unconditioned stimuli to link non-pheromonal stimuli to the pheromonal response, via associative learning. The medial amygdala, has emerged as a potential site for this convergence by which learned chemosensory input is able to gain control over innately-driven output circuits. The medial amygdala is also an important site for associating social chemosensory information that enables recognition of conspecifics and heterospecifics by association of their complex chemosensory signatures both within and across olfactory chemosensory systems. Learning can also influence pheromonal responses more directly to adapt them to changing physiological and behavioural context. Neuromodulators such as noradrenaline and oxytocin can plasticise neural circuits to gate transmission of chemosensory information. More recent evidence points to a role for neurogenesis in this adaptation, both at the peripheral level of the sensory neurons and via the incorporation of new neurons into existing olfactory bulb circuits. The emerging picture is of integrated and flexible responses to chemosignals that adapt them to the environmental and physiological context in which they occur. PMID:25200200

  1. Engineered Trehalose Permeable to Mammalian Cells

    PubMed Central

    Abazari, Alireza; Meimetis, Labros G.; Budin, Ghyslain; Bale, Shyam Sundhar; Weissleder, Ralph; Toner, Mehmet

    2015-01-01

    Trehalose is a naturally occurring disaccharide which is associated with extraordinary stress-tolerance capacity in certain species of unicellular and multicellular organisms. In mammalian cells, presence of intra- and extracellular trehalose has been shown to confer improved tolerance against freezing and desiccation. Since mammalian cells do not synthesize nor import trehalose, the development of novel methods for efficient intracellular delivery of trehalose has been an ongoing investigation. Herein, we studied the membrane permeability of engineered lipophilic derivatives of trehalose. Trehalose conjugated with 6 acetyl groups (trehalose hexaacetate or 6-O-Ac-Tre) demonstrated superior permeability in rat hepatocytes compared with regular trehalose, trehalose diacetate (2-O-Ac-Tre) and trehalose tetraacetate (4-O-Ac-Tre). Once in the cell, intracellular esterases hydrolyzed the 6-O-Ac-Tre molecules, releasing free trehalose into the cytoplasm. The total concentration of intracellular trehalose (plus acetylated variants) reached as high as 10 fold the extracellular concentration of 6-O-Ac-Tre, attaining concentrations suitable for applications in biopreservation. To describe this accumulation phenomenon, a diffusion-reaction model was proposed and the permeability and reaction kinetics of 6-O-Ac-Tre were determined by fitting to experimental data. Further studies suggested that the impact of the loading and the presence of intracellular trehalose on cellular viability and function were negligible. Engineering of trehalose chemical structure rather than manipulating the cell, is an innocuous, cell-friendly method for trehalose delivery, with demonstrated potential for trehalose loading in different types of cells and cell lines, and can facilitate the wide-spread application of trehalose as an intracellular protective agent in biopreservation studies. PMID:26115179

  2. Mechanoaccumulative Elements of the Mammalian Actin Cytoskeleton.

    PubMed

    Schiffhauer, Eric S; Luo, Tianzhi; Mohan, Krithika; Srivastava, Vasudha; Qian, Xuyu; Griffis, Eric R; Iglesias, Pablo A; Robinson, Douglas N

    2016-06-01

    To change shape, divide, form junctions, and migrate, cells reorganize their cytoskeletons in response to changing mechanical environments [1-4]. Actin cytoskeletal elements, including myosin II motors and actin crosslinkers, structurally remodel and activate signaling pathways in response to imposed stresses [5-9]. Recent studies demonstrate the importance of force-dependent structural rearrangement of α-catenin in adherens junctions [10] and vinculin's molecular clutch mechanism in focal adhesions [11]. However, the complete landscape of cytoskeletal mechanoresponsive proteins and the mechanisms by which these elements sense and respond to force remain to be elucidated. To find mechanosensitive elements in mammalian cells, we examined protein relocalization in response to controlled external stresses applied to individual cells. Here, we show that non-muscle myosin II, α-actinin, and filamin accumulate to mechanically stressed regions in cells from diverse lineages. Using reaction-diffusion models for force-sensitive binding, we successfully predicted which mammalian α-actinin and filamin paralogs would be mechanoaccumulative. Furthermore, a "Goldilocks zone" must exist for each protein where the actin-binding affinity must be optimal for accumulation. In addition, we leveraged genetic mutants to gain a molecular understanding of the mechanisms of α-actinin and filamin catch-bonding behavior. Two distinct modes of mechanoaccumulation can be observed: a fast, diffusion-based accumulation and a slower, myosin II-dependent cortical flow phase that acts on proteins with specific binding lifetimes. Finally, we uncovered cell-type- and cell-cycle-stage-specific control of the mechanosensation of myosin IIB, but not myosin IIA or IIC. Overall, these mechanoaccumulative mechanisms drive the cell's response to physical perturbation during proper tissue development and disease. PMID:27185555

  3. Coyote (Canis latrans) mammalian prey diet shifts in response to seasonal vegetation change.

    PubMed

    Seamster, Virginia A; Waits, Lisette P; Macko, Stephen A; Shugart, Herman H

    2014-01-01

    Drylands typically have strong seasonal variation in rainfall and primary productivity. This study examines the effects of seasonal change in grass-derived resource availability on the base of the food chain of a mammalian predator. Seasonal changes in live grass cover were measured in two vegetation types at the Sevilleta National Wildlife Refuge in central New Mexico, USA. Non-invasive genetic sampling of scat was used to identify individuals in the local coyote (Canis latrans) population. Stable carbon and nitrogen isotope analysis of hair removed from scats of 45 different coyotes was used to assess seasonal variation in the diet of mammalian coyote prey that came from C4 grasses. Live grass cover increased from the spring to the summer and fall; contribution of C4 grasses to the diet of mammalian coyote prey increased from the summer to the fall and was higher in grassland areas. There were significant differences in the seasonal patterns in the prey diet between grassland and shrubland areas. PMID:24999056

  4. Modification of N-glycosylation sites allows secretion of bacterial chondroitinase ABC from mammalian cells

    PubMed Central

    Muir, Elizabeth M.; Fyfe, Ian; Gardiner, Sonya; Li, Li; Warren, Philippa; Fawcett, James W.; Keynes, Roger J.; Rogers, John H.

    2010-01-01

    Although many eukaryotic proteins have been secreted by transfected bacterial cells, little is known about how a bacterial protein is treated as it passes through the secretory pathway when expressed in a eukaryotic cell. The eukaryotic N-glycosylation system could interfere with folding and secretion of prokaryotic proteins whose sequence has not been adapted for glycosylation in structurally appropriate locations. Here we show that such interference does indeed occur for chondroitinase ABC from the bacterium Proteus vulgaris, and can be overcome by eliminating potential N-glycosylation sites. Chondroitinase ABC was heavily glycosylated when expressed in mammalian cells or in a mammalian translation system, and this process prevented secretion of functional enzyme. Directed mutagenesis of selected N-glycosylation sites allowed efficient secretion of active chondroitinase. As these proteoglycans are known to inhibit regeneration of axons in the mammalian central nervous system, the modified chondroitinase gene is a potential tool for gene therapy to promote neural regeneration, ultimately in human spinal cord injury. PMID:19900493

  5. MAMMALIAN CELL GENE MUTATION ASSAYS WORKING GROUP REPORT

    EPA Science Inventory

    Mammalian cell gene mutation assays have been used for many years and the diversity of the available systems attests to the varied methods found to grow mammalian dells and detect mutations. s part of the International Workshop on Standardization of Genotoxicity Test Procedures, ...

  6. An Analytical Study of Mammalian Bite Wounds Requiring Inpatient Management

    PubMed Central

    Lee, Young-Geun; Kim, Woo-Kyung

    2013-01-01

    Background Mammalian bite injuries create a public health problem because of their frequency, potential severity, and increasing number. Some researchers have performed fragmentary analyses of bite wounds caused by certain mammalian species. However, little practical information is available concerning serious mammalian bite wounds that require hospitalization and intensive wound management. Therefore, the purpose of this study was to perform a general review of serious mammalian bite wounds. Methods We performed a retrospective review of the medical charts of 68 patients who were referred to our plastic surgery department for the treatment of bite wounds between January 2003 and October 2012. The cases were analyzed according to the species, patient demographics, environmental factors, injury characteristics, and clinical course. Results Among the 68 cases of mammalian bite injury, 58 (85%) were caused by dogs, 8 by humans, and 2 by cats. Most of those bitten by a human and both of those bitten by cats were male. Only one-third of all the patients were children or adolescents. The most frequent site of injury was the face, with 40 cases, followed by the hand, with 16 cases. Of the 68 patients, 7 were treated with secondary intention healing. Sixty-one patients underwent delayed procedures, including delayed direct closure, skin graft, composite graft, and local flap. Conclusions Based on overall findings from our review of the 68 cases of mammalian bites, we suggest practical guidelines for the management of mammalian bite injuries, which could be useful in the treatment of serious mammalian bite wounds. PMID:24286042

  7. Chemical sensing in mammalian host-bacterial commensal associations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mammalian gastrointestinal (GI) tract is colonized by a complex consortium of bacterial species. Bacteria engage in chemical signaling to coordinate population-wide behavior. However, it is unclear if chemical sensing plays a role in establishing mammalian host–bacterial commensal relationships....

  8. Qualification Paths of Adult Educators in Sweden and Denmark

    ERIC Educational Resources Information Center

    Andersson, Per; Kopsen, Susanne; Larson, Anne; Milana, Marcella

    2013-01-01

    The qualification of adult educators is a central aspect of the quality of adult education. However, within current policy discourses and adult education research on the professional development of prospective adult educators, little attention is paid to teacher qualification when compared to other fields of education and training. In this study,…

  9. USE OF NON-MAMMALIAN ALTERNATIVE MODELS FOR NEUROTOXICOLOGICAL STUDY

    PubMed Central

    Peterson, Randall T.; Nass, Richard; Boyd, Windy A.; Freedman, Jonathan H.; Dong, Ke; Narahashi, Toshio

    2009-01-01

    The field of neurotoxicology needs to satisfy two opposing demands: the testing of a growing list of chemicals, and resource limitations and ethical concerns associated with testing using traditional mammalian species. National and international government agencies have defined a need to reduce, refine or replace mammalian species in toxicological testing with alternative testing methods and non-mammalian models. Toxicological assays using alternative animal models may relieve some of this pressure by allowing testing of more compounds while reducing expense and using fewer mammals. Recent advances in genetic technologies and the strong conservation between human and non-mammalian genomes allows for the dissection of the molecular pathways involved in neurotoxicological responses and neurological diseases using genetically tractable organisms. In this review, applications of four non-mammalian species, Zebrafish, cockroach, Drosophila, and Caenorhabditis elegans, in the investigation of neurotoxicology and neurological diseases are presented. PMID:18538410

  10. ATP-Competitive Inhibitors of the Mammalian Target of Rapamycin: Design and Synthesis of Highly Potent and Selective Pyrazolopyrimidines

    SciTech Connect

    Zask, Arie; Verheijen, Jeroen C.; Curran, Kevin; Kaplan, Joshua; Richard, David J.; Nowak, Pawel; Malwitz, David J.; Brooijmans, Natasja; Bard, Joel; Svenson, Kristine; Lucas, Judy; Toral-Barza, Lourdes; Zhang, Wei-Guo; Hollander, Irwin; Gibbons, James J.; Abraham, Robert T.; Ayral-Kaloustian, Semiramis; Mansour, Tarek S.; Yu, Ker

    2009-09-18

    The mammalian target of rapamycin (mTOR), a central regulator of growth, survival, and metabolism, is a validated target for cancer therapy. Rapamycin and its analogues, allosteric inhibitors of mTOR, only partially inhibit one mTOR protein complex. ATP-competitive, global inhibitors of mTOR that have the potential for enhanced anticancer efficacy are described. Structural features leading to potency and selectivity were identified and refined leading to compounds with in vivo efficacy in tumor xenograft models.

  11. Overview of Glutamatergic Dysregulation in Central Pathologies

    PubMed Central

    Miladinovic, Tanya; Nashed, Mina G.; Singh, Gurmit

    2015-01-01

    As the major excitatory neurotransmitter in the mammalian central nervous system, glutamate plays a key role in many central pathologies, including gliomas, psychiatric, neurodevelopmental, and neurodegenerative disorders. Post-mortem and serological studies have implicated glutamatergic dysregulation in these pathologies, and pharmacological modulation of glutamate receptors and transporters has provided further validation for the involvement of glutamate. Furthermore, efforts from genetic, in vitro, and animal studies are actively elucidating the specific glutamatergic mechanisms that contribute to the aetiology of central pathologies. However, details regarding specific mechanisms remain sparse and progress in effectively modulating glutamate to alleviate symptoms or inhibit disease states has been relatively slow. In this report, we review what is currently known about glutamate signalling in central pathologies. We also discuss glutamate’s mediating role in comorbidities, specifically cancer-induced bone pain and depression. PMID:26569330

  12. Adult onset retinoblastoma.

    PubMed

    Sengupta, Sabyasachi; Pan, Utsab; Khetan, Vikas

    2016-07-01

    Retinoblastoma (RB) is the most common primary malignant intraocular tumor of childhood presenting usually before 5 years of age. RB in adults older than 20 years is extremely rare. A literature search using PubMed/PubMed Central, Scopus, Google Scholar, EMBASE, and Cochrane databases revealed only 45 cases till date. Over the past decade, there has been a significant increase in the number of such reports, indicating heightened level of suspicion among ophthalmologists. Compared to its pediatric counterpart, adult onset RB poses unique challenges in diagnosis and treatment. This article summarizes available literature on adult onset RB and its clinical and pathologic profile, genetics, association with retinocytoma, diagnostics, treatment, and outcomes. PMID:27609158

  13. Adult Seborrheic Dermatitis

    PubMed Central

    2011-01-01

    Seborrheic dermatitis is a common chronic-recurrent inflammatory disorder that most commonly affects adults; however, a more transient infantile form also occurs. The definitive cause of seborrheic dermatitis is unknown. However, proliferation of Malassezia species has been described as a contributing factor. The adult form of seborrheic dermatitis affects up to approximately five percent of the general population. The disorder commonly affects the scalp, face, and periauricular region, with the central chest, axillae, and genital region also involved in some cases. Pruritus is not always present and is relatively common, especially with scalp disease. A variety of treatments are available including topical corticosteroids, topical antifungal agents, topical calcineurin inhibitors, and more recently, a nonsteroidal “device ”cream. This article reviews the practical topical management of seborrheic dermatitis in the United States, focusing on the adult population. PMID:21607192

  14. New facets of keratin K77: interspecies variations of expression and different intracellular location in embryonic and adult skin of humans and mice.

    PubMed

    Langbein, Lutz; Reichelt, Julia; Eckhart, Leopold; Praetzel-Wunder, Silke; Kittstein, Walter; Gassler, Nikolaus; Schweizer, Juergen

    2013-12-01

    The differential expression of keratins is central to the formation of various epithelia and their appendages. Structurally, the type II keratin K77 is closely related to K1, the prototypical type II keratin of the suprabasal epidermis. Here, we perform a developmental study on K77 expression in human and murine skin. In both species, K77 is expressed in the suprabasal fetal epidermis. While K77 appears after K1 in the human epidermis, the opposite is true for the murine tissue. This species-specific pattern of expression is also found in conventional and organotypic cultures of human and murine keratinocytes. Ultrastructure investigation shows that, in contrast to K77 intermediate filaments of mice, those of the human ortholog are not attached to desmosomes. After birth, K77 disappears without deleterious consequences from human epidermis while it is maintained in the adult mouse epidermis, where its presence has so far gone unnoticed. After targeted Krt1 gene deletion in mice, K77 is normally expressed but fails to functionally replace K1. Besides the epidermis, both human and mouse K77 are present in luminal duct cells of eccrine sweat glands. The demonstration of a K77 ortholog in platypus but not in non-mammalian vertebrates identifies K77 as an evolutionarily ancient component of the mammalian integument that has evolved different patterns of intracellular distribution and adult tissue expression in primates. PMID:24057875

  15. Prospects for mTOR-mediated functional repair after central nervous system trauma.

    PubMed

    Berry, Martin; Ahmed, Zubair; Morgan-Warren, Peter; Fulton, Daniel; Logan, Ann

    2016-01-01

    Recent research has suggested that the growth of central nervous system (CNS) axons during development is mediated through the PI3K/Akt/mammalian target of rapamycin (mTOR) intracellular signalling axis and that suppression of activity in this pathway occurs during maturity as levels of the phosphatase and tensin homologue (PTEN) rise and inhibit PI3K activation of mTOR, accounting for the failure of axon regeneration in the injured adult CNS. This hypothesis is supported by findings confirming that suppression of PTEN in experimental adult animals promotes impressive axon regeneration in the injured visual and corticospinal motor systems. This review focuses on these recent developments, discussing the therapeutic potential of a mTOR-based treatment aimed at promoting functional recovery in CNS trauma patients, recognising that to fulfil this ambition, the new therapy should aim to promote not only axon regeneration but also remyelination of regenerated axons, neuronal survival and re-innervation of denervated targets through accurate axonal guidance and synaptogenesis, all with minimal adverse effects. The translational challenges presented by the implementation of this new axogenic therapy are also discussed. PMID:26459109

  16. Fine-tuning the central nervous system: microglial modelling of cells and synapses

    PubMed Central

    Xavier, Anna L.; Menezes, João R. L.; Goldman, Steven A.; Nedergaard, Maiken

    2014-01-01

    Microglia constitute as much as 10–15% of all cells in the mammalian central nervous system (CNS) and are the only glial cells that do not arise from the neuroectoderm. As the principal CNS immune cells, microglial cells represent the first line of defence in response to exogenous threats. Past studies have largely been dedicated to defining the complex immune functions of microglial cells. However, our understanding of the roles of microglia has expanded radically over the past years. It is now clear that microglia are critically involved in shaping neural circuits in both the developing and adult CNS, and in modulating synaptic transmission in the adult brain. Intriguingly, microglial cells appear to use the same sets of tools, including cytokine and chemokine release as well as phagocytosis, whether modulating neural function or mediating the brain's innate immune responses. This review will discuss recent developments that have broadened our views of neuro-glial signalling to include the contribution of microglial cells. PMID:25225087

  17. ATM localization and gene expression in the adult mouse eye

    PubMed Central

    Leemput, Julia; Masson, Christel; Bigot, Karine; Errachid, Abdelmounaim; Dansault, Anouk; Provost, Alexandra; Gadin, Stéphanie; Aoufouchi, Said; Menasche, Maurice

    2009-01-01

    Purpose High levels of metabolism and oxygen consumption in most adult murine ocular compartments, combined with exposure to light and ultraviolet (UV) radiation, are major sources of oxidative stress, causing DNA damage in ocular cells. Of all mammalian body cells, photoreceptor cells consume the largest amount of oxygen and generate the highest levels of oxidative damage. The accumulation of such damage throughout life is a major factor of aging tissues. Several multiprotein complexes have recently been identified as the major sensors and mediators involved in the maintenance of DNA integrity. The activity of these complexes initially seemed to be restricted to dividing cells, given their ultimate role in major cell cycle checkpoints. However, it was later established that they are also active in post-mitotic cells. Recent findings demonstrate that the DNA damage response (DDR) is essential for the development, maintenance, and normal functioning of the adult central nervous system. One major molecular factor in the DDR is the protein, ataxia telangiectasia mutated (ATM). It is required for the rapid induction of cellular responses to DNA double-strand breaks. These cytotoxic DNA lesions may be caused by oxidative damage. To understand how ATM prevents oxidative stress and participates in the maintenance of genomic integrity and cell viability of the adult retina, we determined the ATM expression patterns and studied its localization in the adult mouse eye. Methods Atm gene expression was analyzed by RT–PCR experiments and its localization by in situ hybridization on adult mouse ocular and cerebellar tissue sections. ATM protein expression was determined by western blot analysis of proteins homogenates extracted from several mouse tissues and its localization by immunohistochemistry experiments performed on adult mouse ocular and cerebellar tissue sections. In addition, subcellular localization was realized by confocal microscopy imaging of ocular tissue

  18. Deer antlers as a model of Mammalian regeneration.

    PubMed

    Price, Joanna; Faucheux, Corrine; Allen, Steve

    2005-01-01

    regenerate antlers lies in the particular cues to which multipotential progenitor/stem cells in an antler's 'regeneration territory' are exposed. This in turn suggests that with appropriate manipulation of the environment, pluripotential cells in other adult mammalian tissues could be stimulated to increase the healing capacity of organs, even if not to regenerate them completely. The need for replacement organs in humans is substantial. The benefits of increasing individuals' own capacity for regeneration and repair are self evident. PMID:15949530

  19. Association of immunophilins with mammalian TRPC channels.

    PubMed

    Sinkins, William G; Goel, Monu; Estacion, Mark; Schilling, William P

    2004-08-13

    Drosophila photoreceptor channels TRP and TRPL are held in a large signalplex by the scaffolding protein, INAD. Immunophilin FKBP59, another member of the signalplex, binds to both INAD and TRPL. Mutation P702Q or P709Q in the highly conserved TRPL sequence (701)LPPPFNVLP(709), eliminates TRPL interaction with FKBP59. The first leucylprolyl (LP) dipeptide in this region is conserved in mammalian TRPC channel proteins. However, the second LP is changed to isoleucylprolyl (IP) in TRPC1, -C4, and -C5, and valylprolyl (VP) in TRPC3, -C6, and -C7. The purpose of the present study was to determine if mammalian FKBP12 or FKBP52 interact with TRPC channel proteins. Using TRPC-specific antibodies, immunoprecipitations from Sf9 cells individually co-expressing each of the TRPC proteins along with the immunophilins showed that TRPC3, -C6, and -C7 interact with FKBP12, whereas TRPC1, -C4, and -C5 interact with FKBP52. The binding of FKBP12 and FKBP52 was specific and could be displaced by the immunosuppressant drug FK506, at concentrations of 0.5 and 10 microm, respectively. To evaluate TRPC-immunophilin interactions in vivo, immunoprecipitations were performed using membrane lysates of rat cerebral cortex. FKBP12 co-immunoprecipitated with TRPC3, -C6, and -C7 from rat brain, whereas FKBP52 was found to associate with TRPC1, -C4, and -C5. The association of immunophilins with the TRPC channels in rat brain lysates could be displaced by FK506. Receptor-mediated activation of TRPC6, stably expressed in HEK cells, was significantly inhibited by FK506, which also disrupted interaction between TRPC6 and the endogenous immunophilin found in HEK cells. Pro to Gln mutations in the first LP dipeptide in the putative FKBP binding domain eliminated FKBP12 and FKBP52 interaction with TRPC3 and -C6, and TRPC1 and -C4, respectively. However, mutual swap of VP and IP in TRPC3 and TRPC5 did not alter the association or the selectivity of the channels for their respective immunophilin binding

  20. Mammalian ion-coupled solute transporters.

    PubMed Central

    Hediger, M A; Kanai, Y; You, G; Nussberger, S

    1995-01-01

    Active transport of solutes into and out of cells proceeds via specialized transporters that utilize diverse energy-coupling mechanisms. Ion-coupled transporters link uphill solute transport to downhill electrochemical ion gradients. In mammals, these transporters are coupled to the co-transport of H+, Na+, Cl- and/or to the countertransport of K+ or OH-. By contrast, ATP-dependent transporters are directly energized by the hydrolysis of ATP. The development of expression cloning approaches to select cDNA clones solely based on their capacity to induce transport function in Xenopus oocytes has led to the cloning of several ion-coupled transporter cDNAs and revealed new insights into structural designs, energy-coupling mechanisms and physiological relevance of the transporter proteins. Different types of mammalian ion-coupled transporters are illustrated by discussing transporters isolated in our own laboratory such as the Na+/glucose co-transporters SGLT1 and SGLT2, the H(+)-coupled oligopeptide transporters PepT1 and PepT2, and the Na(+)- and K(+)-dependent neuronal and epithelial high affinity glutamate transporter EAAC1. Most mammalian ion-coupled organic solute transporters studied so far can be grouped into the following transporter families: (1) the predominantly Na(+)-coupled transporter family which includes the Na+/glucose co-transporters SGLT1, SGLT2, SGLT3 (SAAT-pSGLT2) and the inositol transporter SMIT, (2) the Na(+)- and Cl(-)-coupled transporter family which includes the neurotransmitter transporters of gamma-amino-butyric acid (GABA), serotonin, dopamine, norepinephrine, glycine and proline as well as transporters of beta-amino acids, (3) the Na(+)- and K(+)-dependent glutamate/neurotransmitter family which includes the high affinity glutamate transporters EAAC1, GLT-1, GLAST, EAAT4 and the neutral amino acid transporters ASCT1 and SATT1 reminiscent of system ASC and (4) the H(+)-coupled oligopeptide transporter family which includes the intestinal H

  1. Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns.

    PubMed

    Machado, João Paulo; Philip, Siby; Maldonado, Emanuel; O'Brien, Stephen J; Johnson, Warren E; Antunes, Agostinho

    2016-01-01

    A diverse group of genes are involved in the tooth development of mammals. Several studies, focused mainly on mice and rats, have provided a detailed depiction of the processes coordinating tooth formation and shape. Here we surveyed 236 tooth-associated genes in 39 mammalian genomes and tested for signatures of selection to assess patterns of molecular adaptation in genes regulating mammalian dentition. Of the 236 genes, 31 (∼13.1%) showed strong signatures of positive selection that may be responsible for the phenotypic diversity observed in mammalian dentition. Mammalian-specific tooth-associated genes had accelerated mutation rates compared with older genes found across all vertebrates. More recently evolved genes had fewer interactions (either genetic or physical), were associated with fewer Gene Ontology terms and had faster evolutionary rates compared with older genes. The introns of these positively selected genes also exhibited accelerated evolutionary rates, which may reflect additional adaptive pressure in the intronic regions that are associated with regulatory processes that influence tooth-gene networks. The positively selected genes were mainly involved in processes like mineralization and structural organization of tooth specific tissues such as enamel and dentin. Of the 236 analyzed genes, 12 mammalian-specific genes (younger genes) provided insights on diversification of mammalian teeth as they have higher evolutionary rates and exhibit different expression profiles compared with older genes. Our results suggest that the evolution and development of mammalian dentition occurred in part through positive selection acting on genes that previously had other functions. PMID:27613398

  2. Assessment of adult neurogenesis in mice.

    PubMed

    Pan, Yung-Wei; Wang, Wenbin; Xia, Zhengui

    2013-05-01

    Adult neurogenesis is a lifelong developmental process that occurs in two discrete regions in the adult mammalian brain: the subgranular zone of the dentate gyrus (DG) and the subventricular zone (SVZ) along the lateral ventricles. Despite immense interest in the therapeutic potential of adult neural stem cells (aNSCs) residing along these two neurogenic regions, molecular and cellular mechanisms regulating this process are not fully defined. Defining the regulatory mechanisms responsible for the genesis of new neurons in the adult brain is integral to understanding the basic biology of aNSCs. The techniques described here provide a basic blueprint to isolate, culture, and perform experiments using aNSCs in vitro as well as providing methods to perform immunohistochemistry on brain sections. Curr. Protoc. Toxicol. 56:12.20.1-12.20.16. © 2013 by John Wiley & Sons, Inc. PMID:23670864

  3. Central Italy

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Clouds and haze cover most of the Italian peninsula in this view of central Italy (41.5N, 14.0E) but the Bay of Naples region with Mt. Vesuvius and the island of Capri are clear. The Adriatic Sea in the background separates Italy from the cloud covered Balkans of eastern Europe and the Tyrrhenian Sea in the foreground lies between the Italian mainland and the off scene islands of Corsica and Sardinia. Several aircraft contrails can also be seen.

  4. Two Ancient Gene Families Are Critical for Maintenance of the Mammalian Skin Barrier in Postnatal Life.

    PubMed

    Cangkrama, Michael; Darido, Charbel; Georgy, Smitha R; Partridge, Darren; Auden, Alana; Srivastava, Seema; Wilanowski, Tomasz; Jane, Stephen M

    2016-07-01

    The skin barrier is critical for mammalian survival in the terrestrial environment, affording protection against fluid loss, microbes, toxins, and UV exposure. Many genes indispensable for barrier formation in the embryo have been identified, but loss of these genes in adult mice does not induce barrier regression. We describe a complex regulatory network centered on two ancient gene families, the grainyhead-like (Grhl) transcription factors and the protein cross-linking enzymes (tissue transglutaminases [Tgms]), which are essential for skin permeability barrier maintenance in adult mice. Embryonic deletion of Grhl3 induces loss of Tgm1 expression, which disrupts the cornified envelope, thus preventing permeability barrier formation leading to neonatal death. However, gene deletion of Grhl3 in adult mice does not disrupt the preformed barrier, with cornified envelope integrity maintained by Grhl1 and Tgm5, which are up-regulated in response to postnatal loss of Grhl3. Concomitant deletion of both Grhl factors in adult mice induced loss of Tgm1 and Tgm5 expression, perturbation of the cornified envelope, and complete permeability barrier regression that was incompatible with life. These findings define the molecular safeguards for barrier function that accompany the transition from intrauterine to terrestrial life. PMID:26975724

  5. Expression of DMRT1 in the mammalian ovary and testis--from marsupials to mice.

    PubMed

    Pask, A J; Behringer, R R; Renfree, M B

    2003-01-01

    Doublesex and mab3 related transcript (DMRT1) was identified as a candidate gene for human 9p24.3 associated sex reversal. DMRT1 orthologues have highly conserved roles in sexual differentiation from flies and worms to humans. A DMRT1 orthologue was isolated from a marsupial, the tammar wallaby Macropus eugenii. The wallaby gene is highly conserved with other vertebrate DMRT1 genes, especially within the P/S and DM domains. It is expressed in the differentiating testis from the late fetus, during pouch life and in the adult. As in eutherian mammals, DMRT1 protein was localized in the germ cells and the Sertoli cells of the testis, but in addition it was detected in the Leydig cells, peri-tubular myoid cells and within the acrosome of the sperm heads. DMRT1 protein was also detected in the fetal and adult ovary pre-granulosa, granulosa and germ cells. Similarly, we also detected DMRT1 in the granulosa cells of all developing follicles in the adult mouse ovary. This is the first report of DMRT1 expression in the adult mammalian ovary, and suggests a wider role for this gene in mammals, in both the testis and ovarian function. PMID:14684988

  6. Mammalian Cardiac Regeneration After Fetal Myocardial Infarction Requires Cardiac Progenitor Cell Recruitment

    PubMed Central

    Allukian, Myron; Xu, Junwang; Morris, Michael; Caskey, Robert; Dorsett-Martin, Wanda; Plappert, Theodore; Griswold, Michael; Gorman, Joseph H.; Gorman, Robert C.; Liechty, Kenneth W.

    2013-01-01

    Background In contrast to the adult, fetal sheep consistently regenerate functional myocardium after myocardial infarction. We hypothesize that this regeneration is due to the recruitment of cardiac progenitor cells to the infarct by stromal-derived factor-1α (SDF-1α) and that its competitive inhibition will block the regenerative fetal response. Methods A 20% apical infarct was created in adult and fetal sheep by selective permanent coronary artery ligation. Lentiviral overexpression of mutant SDF-1α competitively inhibited SDF-1α in fetal infarcts. Echocardiography was performed to assess left ventricular function and infarct size. Cardiac progenitor cell recruitment and proliferation was assessed in fetal infarcts at 1 month by immunohistochemistry for nkx2.5 and 5-bromo-2-deoxyuridine. Results Competitive inhibition of SDF-1α converted the regenerative fetal response into a reparative response, similar to the adult. SDF-inhibited fetal infarcts demonstrated significant infarct expansion by echocardiography (p < 0.001) and a significant decrease in the number of nkx2.5+ cells repopulating the infarct (p < 0.001). Conclusions The fetal regenerative response to myocardial infarction requires the recruitment of cardiac progenitor cells and is dependent on SDF1α. This novel model of mammalian cardiac regeneration after myocardial infarction provides a powerful tool to better understand cardiac progenitor cell biology and to develop strategies to cardiac regeneration in the adult. PMID:23816072

  7. Adult stem cell maintenance and tissue regeneration in the ageing context: the role for A-type lamins as intrinsic modulators of ageing in adult stem cells and their niches

    PubMed Central

    Pekovic, Vanja; Hutchison, Christopher J

    2008-01-01

    Adult stem cells have been identified in most mammalian tissues of the adult body and are known to support the continuous repair and regeneration of tissues. A generalized decline in tissue regenerative responses associated with age is believed to result from a depletion and/or a loss of function of adult stem cells, which itself may be a driving cause of many age-related disease pathologies. Here we review the striking similarities between tissue phenotypes seen in many degenerative conditions associated with old age and those reported in age-related nuclear envelope disorders caused by mutations in the LMNA gene. The concept is beginning to emerge that nuclear filament proteins, A-type lamins, may act as signalling receptors in the nucleus required for receiving and/or transducing upstream cytosolic signals in a number of pathways central to adult stem cell maintenance as well as adaptive responses to stress. We propose that during ageing and in diseases caused by lamin A mutations, dysfunction of the A-type lamin stress-resistant signalling network in adult stem cells, their progenitors and/or stem cell niches leads to a loss of protection against growth-related stress. This in turn triggers an inappropriate activation or a complete failure of self-renewal pathways with the consequent initiation of stress-induced senescence. As such, A-type lamins should be regarded as intrinsic modulators of ageing within adult stem cells and their niches that are essential for survival to old age. PMID:18638067

  8. Maintenance and Expression of Mammalian Mitochondrial DNA.

    PubMed

    Gustafsson, Claes M; Falkenberg, Maria; Larsson, Nils-Göran

    2016-06-01

    Mammalian mitochondrial DNA (mtDNA) encodes 13 proteins that are essential for the function of the oxidative phosphorylation system, which is composed of four respiratory-chain complexes and adenosine triphosphate (ATP) synthase. Remarkably, the maintenance and expression of mtDNA depend on the mitochondrial import of hundreds of nuclear-encoded proteins that control genome maintenance, replication, transcription, RNA maturation, and mitochondrial translation. The importance of this complex regulatory system is underscored by the identification of numerous mutations of nuclear genes that impair mtDNA maintenance and expression at different levels, causing human mitochondrial diseases with pleiotropic clinical manifestations. The basic scientific understanding of the mechanisms controlling mtDNA function has progressed considerably during the past few years, thanks to advances in biochemistry, genetics, and structural biology. The challenges for the future will be to understand how mtDNA maintenance and expression are regulated and to what extent direct intramitochondrial cross talk between different processes, such as transcription and translation, is important. PMID:27023847

  9. Sources of Error in Mammalian Genetic Screens

    PubMed Central

    Sack, Laura Magill; Davoli, Teresa; Xu, Qikai; Li, Mamie Z.; Elledge, Stephen J.

    2016-01-01

    Genetic screens are invaluable tools for dissection of biological phenomena. Optimization of such screens to enhance discovery of candidate genes and minimize false positives is thus a critical aim. Here, we report several sources of error common to pooled genetic screening techniques used in mammalian cell culture systems, and demonstrate methods to eliminate these errors. We find that reverse transcriptase-mediated recombination during retroviral replication can lead to uncoupling of molecular tags, such as DNA barcodes (BCs), from their associated library elements, leading to chimeric proviral genomes in which BCs are paired to incorrect ORFs, shRNAs, etc. This effect depends on the length of homologous sequence between unique elements, and can be minimized with careful vector design. Furthermore, we report that residual plasmid DNA from viral packaging procedures can contaminate transduced cells. These plasmids serve as additional copies of the PCR template during library amplification, resulting in substantial inaccuracies in measurement of initial reference populations for screen normalization. The overabundance of template in some samples causes an imbalance between PCR cycles of contaminated and uncontaminated samples, which results in a systematic artifactual depletion of GC-rich library elements. Elimination of contaminating plasmid DNA using the bacterial endonuclease Benzonase can restore faithful measurements of template abundance and minimize GC bias. PMID:27402361

  10. Myocardial ischemic protection in natural mammalian hibernation

    PubMed Central

    Yan, Lin; Kudej, Raymond K.; Vatner, Dorothy E.

    2015-01-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation. PMID:25613166

  11. From Immunity and Vaccines to Mammalian Regeneration

    PubMed Central

    Heber-Katz, Ellen

    2015-01-01

    Our current understanding of major histocompatibility complex (MHC)-mediated antigen presentation in self and nonself immune recognition was derived from immunological studies of autoimmunity and virus-host interactions, respectively. The trimolecular complex of the MHC molecule, antigen, and T-cell receptor accounts for the phenomena of immunodominance and MHC degeneracy in both types of responses and constrains vaccine development. Out of such considerations, we developed a simple peptide vaccine construct that obviates immunodominance, resulting in a broadly protective T-cell response in the absence of antibody. In the course of autoimmunity studies, we identified the MRL mouse strain as a mammalian model of amphibian-like regeneration. A significant level of DNA damage in the cells from this mouse pointed to the role of the cell cycle checkpoint gene CDKN1a, or p21cip1/waf1. The MRL mouse has highly reduced levels of this molecule, and a genetic knockout of this single gene in otherwise nonregenerating strains led to an MRL-type regenerative response, indicating that the ability to regenerate has not been lost during evolution. PMID:26116734

  12. Mammalian meiotic silencing exhibits sexually dimorphic features.

    PubMed

    Cloutier, J M; Mahadevaiah, S K; ElInati, E; Tóth, A; Turner, James

    2016-06-01

    During mammalian meiotic prophase I, surveillance mechanisms exist to ensure that germ cells with defective synapsis or recombination are eliminated, thereby preventing the generation of aneuploid gametes and embryos. Meiosis in females is more error-prone than in males, and this is in part because the prophase I surveillance mechanisms are less efficient in females. A mechanistic understanding of this sexual dimorphism is currently lacking. In both sexes, asynapsed chromosomes are transcriptionally inactivated by ATR-dependent phosphorylation of histone H2AFX. This process, termed meiotic silencing, has been proposed to perform an important prophase I surveillance role. While the transcriptional effects of meiotic silencing at individual genes are well described in the male germ line, analogous studies in the female germ line have not been performed. Here we apply single- and multigene RNA fluorescence in situ hybridization (RNA FISH) to oocytes from chromosomally abnormal mouse models to uncover potential sex differences in the silencing response. Notably, we find that meiotic silencing in females is less efficient than in males. Within individual oocytes, genes located on the same asynapsed chromosome are silenced to differing extents, thereby generating mosaicism in gene expression profiles across oocyte populations. Analysis of sex-reversed XY female mice reveals that the sexual dimorphism in silencing is determined by gonadal sex rather than sex chromosome constitution. We propose that sex differences in meiotic silencing impact on the sexually dimorphic prophase I response to asynapsis. PMID:26712235

  13. ORC proteins in the mammalian zygote.

    PubMed

    Ortega, Michael A; Nguyen, Hieu; Ward, W Steven

    2016-01-01

    The origin recognition complex (ORC) proteins, ORC1-6, are the first known proteins that bind DNA replication origins to mark the competency for the initiation of DNA synthesis. These proteins have complex mechanisms of assembly into the ORC complex and unexpected localizations in the mitotic chromosomes, cytoplasm, and nuclear structures. The mammalian zygote is a potentially important model that may contribute to our understanding of the mechanisms and features influencing origin establishment and in the identification of other functions of the ORC proteins. Together with expected localizations to the chromatin during G1, we found an unexpected distribution in the cytoplasm that appeared to accumulate ORC proteins suggesting potential roles for ORC subunits in mitosis and chromatin segregation. ORC1, 2, 3, and 5 all localize to the area between the separating maternal chromosomes shortly after fertilization. ORC4 forms a cage around the set of chromosomes that will be extruded during polar body formation before it binds to the chromatin shortly before zygotic DNA replication. These data suggest that the ORC proteins may also play roles in preparing the cell for DNA replication in addition to their direct role in establishing functional replication origins. PMID:26453397

  14. Mammalian cells defective in DNA mismatch correction

    SciTech Connect

    Branch, P.; Aquilina, G.; Hess, P.

    1994-12-31

    Mammalian cells counteract the cytotoxicity of methylating agents, including some used in antitumor chemotherapy, by removing the methylated base, O{sup 6}-methylguanine (O{sup 6}-meG) from their DNA. This removal is normally effected by a specific DNA repair enzyme (O{sup 6}-meG-DNA methyltransferase) that is expressed constitutively. In addition, an alternative type of resistance to methylating agents can be acquired after exposure of cells to the drug. This acquired resistance is highly specific for O{sup 6}-meG and is unusual in that alkylation of DNA is normal and there is no increase in the rate of repair of O{sup 6}-meG or any other damaged base. Instead, the cell is able to tolerate the presence of the usually cytotoxic O{sup 6}-meG and to replicate its DNA normally. The ambiguity of base pairing by O{sup 6}-meG and the observation that tolerant cells are also cross-resistant to the structurally similar 6-thioguanine in DNA has led to the suggestion that the cytotoxicity of O{sup 6}-meG (and 6-thioguanine) arises from ineffective attempts at DNA mismatch correction. This model postulates that tolerance arises as a consequence of loss of this important pathway.

  15. RNAi microarray analysis in cultured mammalian cells.

    PubMed

    Mousses, Spyro; Caplen, Natasha J; Cornelison, Robert; Weaver, Don; Basik, Mark; Hautaniemi, Sampsa; Elkahloun, Abdel G; Lotufo, Roberto A; Choudary, Ashish; Dougherty, Edward R; Suh, Ed; Kallioniemi, Olli

    2003-10-01

    RNA interference (RNAi) mediated by small interfering RNAs (siRNAs) is a powerful new tool for analyzing gene knockdown phenotypes in living mammalian cells. To facilitate large-scale, high-throughput functional genomics studies using RNAi, we have developed a microarray-based technology for highly parallel analysis. Specifically, siRNAs in a transfection matrix were first arrayed on glass slides, overlaid with a monolayer of adherent cells, incubated to allow reverse transfection, and assessed for the effects of gene silencing by digital image analysis at a single cell level. Validation experiments with HeLa cells stably expressing GFP showed spatially confined, sequence-specific, time- and dose-dependent inhibition of green fluorescence for those cells growing directly on microspots containing siRNA targeting the GFP sequence. Microarray-based siRNA transfections analyzed with a custom-made quantitative image analysis system produced results that were identical to those from traditional well-based transfection, quantified by flow cytometry. Finally, to integrate experimental details, image analysis, data display, and data archiving, we developed a prototype information management system for high-throughput cell-based analyses. In summary, this RNAi microarray platform, together with ongoing efforts to develop large-scale human siRNA libraries, should facilitate genomic-scale cell-based analyses of gene function. PMID:14525932

  16. Sources of Error in Mammalian Genetic Screens.

    PubMed

    Sack, Laura Magill; Davoli, Teresa; Xu, Qikai; Li, Mamie Z; Elledge, Stephen J

    2016-01-01

    Genetic screens are invaluable tools for dissection of biological phenomena. Optimization of such screens to enhance discovery of candidate genes and minimize false positives is thus a critical aim. Here, we report several sources of error common to pooled genetic screening techniques used in mammalian cell culture systems, and demonstrate methods to eliminate these errors. We find that reverse transcriptase-mediated recombination during retroviral replication can lead to uncoupling of molecular tags, such as DNA barcodes (BCs), from their associated library elements, leading to chimeric proviral genomes in which BCs are paired to incorrect ORFs, shRNAs, etc This effect depends on the length of homologous sequence between unique elements, and can be minimized with careful vector design. Furthermore, we report that residual plasmid DNA from viral packaging procedures can contaminate transduced cells. These plasmids serve as additional copies of the PCR template during library amplification, resulting in substantial inaccuracies in measurement of initial reference populations for screen normalization. The overabundance of template in some samples causes an imbalance between PCR cycles of contaminated and uncontaminated samples, which results in a systematic artifactual depletion of GC-rich library elements. Elimination of contaminating plasmid DNA using the bacterial endonuclease Benzonase can restore faithful measurements of template abundance and minimize GC bias. PMID:27402361

  17. The First Mammalian Aldehyde Oxidase Crystal Structure

    PubMed Central

    Coelho, Catarina; Mahro, Martin; Trincão, José; Carvalho, Alexandra T. P.; Ramos, Maria João; Terao, Mineko; Garattini, Enrico; Leimkühler, Silke; Romão, Maria João

    2012-01-01

    Aldehyde oxidases (AOXs) are homodimeric proteins belonging to the xanthine oxidase family of molybdenum-containing enzymes. Each 150-kDa monomer contains a FAD redox cofactor, two spectroscopically distinct [2Fe-2S] clusters, and a molybdenum cofactor located within the protein active site. AOXs are characterized by broad range substrate specificity, oxidizing different aldehydes and aromatic N-heterocycles. Despite increasing recognition of its role in the metabolism of drugs and xenobiotics, the physiological function of the protein is still largely unknown. We have crystallized and solved the crystal structure of mouse liver aldehyde oxidase 3 to 2.9 Å. This is the first mammalian AOX whose structure has been solved. The structure provides important insights into the protein active center and further evidence on the catalytic differences characterizing AOX and xanthine oxidoreductase. The mouse liver aldehyde oxidase 3 three-dimensional structure combined with kinetic, mutagenesis data, molecular docking, and molecular dynamics studies make a decisive contribution to understand the molecular basis of its rather broad substrate specificity. PMID:23019336

  18. Cell fate regulation in early mammalian development

    NASA Astrophysics Data System (ADS)

    Oron, Efrat; Ivanova, Natalia

    2012-08-01

    Preimplantation development in mammals encompasses a period from fertilization to implantation and results in formation of a blastocyst composed of three distinct cell lineages: epiblast, trophectoderm and primitive endoderm. The epiblast gives rise to the organism, while the trophectoderm and the primitive endoderm contribute to extraembryonic tissues that support embryo development after implantation. In many vertebrates, such as frog or fish, maternally supplied lineage determinants are partitioned within the egg. Cell cleavage that follows fertilization results in polarization of these factors between the individual blastomeres, which become restricted in their developmental fate. In contrast, the mouse oocyte and zygote lack clear polarity and, until the eight-cell stage, individual blastomeres retain the potential to form all lineages. How are cell lineages specified in the absence of a maternally supplied blueprint? This is a fundamental question in the field of developmental biology. The answer to this question lies in understanding the cell-cell interactions and gene networks involved in embryonic development prior to implantation and using this knowledge to create testable models of the developmental processes that govern cell fates. We provide an overview of classic and contemporary models of early lineage development in the mouse and discuss the emerging body of work that highlights similarities and differences between blastocyst development in the mouse and other mammalian species.

  19. Myocardial ischemic protection in natural mammalian hibernation.

    PubMed

    Yan, Lin; Kudej, Raymond K; Vatner, Dorothy E; Vatner, Stephen F

    2015-03-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation. PMID:25613166

  20. Evidence for compartmentalization of mammalian carotenoid metabolism

    PubMed Central

    Palczewski, Grzegorz; Amengual, Jaume; Hoppel, Charles L.; von Lintig, Johannes

    2014-01-01

    The critical role of retinoids (vitamin A and its derivatives) for vision, reproduction, and survival has been well established. Vitamin A is produced from dietary carotenoids such as β-carotene by centric cleavage via the enzyme BCO1. The biochemical and molecular identification of a second structurally related β-carotene metabolizing enzyme, BCO2, has led to a prolonged debate about its relevance in vitamin A biology. While BCO1 cleaves provitamin A carotenoids, BCO2 is more promiscuous and also metabolizes nonprovitamin A carotenoids such as zeaxanthin into long-chain apo-carotenoids. Herein we demonstrate, in cell lines, that human BCO2 is associated with the inner mitochondrial membrane. Different human BCO2 isoforms possess cleavable N-terminal leader sequences critical for mitochondrial import. Subfractionation of murine hepatic mitochondria confirmed the localization of BCO2 to the inner mitochondrial membrane. Studies in BCO2-knockout mice revealed that zeaxanthin accumulates in the inner mitochondrial membrane; in contrast, β-carotene is retained predominantly in the cytoplasm. Thus, we provide evidence for a compartmentalization of carotenoid metabolism that prevents competition between BCO1 and BCO2 for the provitamin and the production of noncanonical β-carotene metabolites.—Palczewski, G., Amengual, J., Hoppel, C. L., von Lintig, J. Evidence for compartmentalization of mammalian carotenoid metabolism. PMID:25002123

  1. Mammalian oocyte growth and development in vitro.

    PubMed

    Eppig, J J; O'Brien, M; Wigglesworth, K

    1996-06-01

    This paper is a review of the current status of technology for mammalian oocyte growth and development in vitro. It compares and contrasts the characteristics of the various culture systems that have been devised for the culture of either isolated preantral follicles or the oocyte-granulosa cell complexes form preantral follicles. The advantages and disadvantages of these various systems are discussed. Endpoints for the evaluation of oocyte development in vitro, including oocyte maturation and embryogenesis, are described. Considerations for the improvement of the culture systems are also presented. These include discussions of the possible effects of apoptosis and inappropriate differentiation of oocyte-associated granulosa cells on oocyte development. Finally, the potential applications of the technology for oocyte growth and development in vitro are discussed. For example, studies of oocyte development in vitro could help to identify specific molecules produced during oocyte development that are essential for normal early embryogenesis and perhaps recognize defects leading to infertility or abnormalities in embryonic development. Moreover, the culture systems may provide the methods necessary to enlarge the populations of valuable agricultural, pharmaceutical product-producing, and endangered animals, and to rescue the oocytes of women about to undergo clinical procedures that place oocytes at risk. PMID:9115726

  2. Presence of thiamine pyrophosphate in mammalian peroxisomes

    PubMed Central

    Fraccascia, Patrizia; Sniekers, Mieke; Casteels, Minne; Van Veldhoven, Paul P

    2007-01-01

    Background Thiamine pyrophosphate (TPP) is a cofactor for 2-hydroxyacyl-CoA lyase 1 (HACL1), a peroxisomal enzyme essential for the α-oxidation of phytanic acid and 2-hydroxy straight chain fatty acids. So far, HACL1 is the only known peroxisomal TPP-dependent enzyme in mammals. Little is known about the transport of metabolites and cofactors across the peroxisomal membrane and no peroxisomal thiamine or TPP carrier has been identified in mammals yet. This study was undertaken to get a better insight into these issues and to shed light on the role of TPP in peroxisomal metabolism. Results Because of the crucial role of the cofactor TPP, we reanalyzed its subcellular localization in rat liver. In addition to the known mitochondrial and cytosolic pools, we demonstrated, for the first time, that peroxisomes contain TPP (177 ± 2 pmol/mg protein). Subsequently, we verified whether TPP could be synthesized from its precursor thiamine, in situ, by a peroxisomal thiamine pyrophosphokinase (TPK). However, TPK activity was exclusively recovered in the cytosol. Conclusion Our results clearly indicate that mammalian peroxisomes do contain TPP but that no pyrophosphorylation of thiamine occurs in these organelles, implying that thiamine must enter the peroxisome already pyrophosphorylated. Consequently, TPP entry may depend on a specific transport system or, in a bound form, on HACL1 translocation. PMID:17596263

  3. Hibernation and daily torpor minimize mammalian extinctions

    NASA Astrophysics Data System (ADS)

    Geiser, Fritz; Turbill, Christopher

    2009-10-01

    Small mammals appear to be less vulnerable to extinction than large species, but the underlying reasons are poorly understood. Here, we provide evidence that almost all (93.5%) of 61 recently extinct mammal species were homeothermic, maintaining a constant high body temperature and thus energy expenditure, which demands a high intake of food, long foraging times, and thus exposure to predators. In contrast, only 6.5% of extinct mammals were likely heterothermic and employed multi-day torpor (hibernation) or daily torpor, even though torpor is widespread within more than half of all mammalian orders. Torpor is characterized by substantial reductions of body temperature and energy expenditure and enhances survival during adverse conditions by minimizing food and water requirements, and consequently reduces foraging requirements and exposure to predators. Moreover, because life span is generally longer in heterothermic mammals than in related homeotherms, heterotherms can employ a ‘sit-and-wait’ strategy to withstand adverse periods and then repopulate when circumstances improve. Thus, torpor is a crucial but hitherto unappreciated attribute of small mammals for avoiding extinction. Many opportunistic heterothermic species, because of their plastic energetic requirements, may also stand a better chance of future survival than homeothermic species in the face of greater climatic extremes and changes in environmental conditions caused by global warming.

  4. Apoptosis in mammalian oocytes: a review.

    PubMed

    Tiwari, Meenakshi; Prasad, Shilpa; Tripathi, Anima; Pandey, Ashutosh N; Ali, Irfan; Singh, Arvind K; Shrivastav, Tulsidas G; Chaube, Shail K

    2015-08-01

    Apoptosis causes elimination of more than 99% of germ cells from cohort of ovary through follicular atresia. Less than 1% of germ cells, which are culminated in oocytes further undergo apoptosis during last phases of oogenesis and depletes ovarian reserve in most of the mammalian species including human. There are several players that induce apoptosis directly or indirectly in oocytes at various stages of meiotic cell cycle. Premature removal of encircling granulosa cells from immature oocytes, reduced levels of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, increased levels of calcium (Ca(2+)) and oxidants, sustained reduced level of maturation promoting factor, depletion of survival factors, nutrients and cell cycle proteins, reduced meiotic competency, increased levels of proapoptotic as well as apoptotic factors lead to oocyte apoptosis. The BH3-only proteins also act as key regulators of apoptosis in oocyte within the ovary. Both intrinsic (mitochondria-mediated) as well as extrinsic (cell surface death receptor-mediated) pathways are involved in oocyte apoptosis. BID, a BH3-only protein act as a bridge between both apoptotic pathways and its cleavage activates cell death machinery of both the pathways inside the follicular microenvironment. Oocyte apoptosis leads to the depletion of ovarian reserve that directly affects reproductive outcome of various mammals including human. In this review article, we highlight some of the important players and describe the pathways involved during oocyte apoptosis in mammals. PMID:25958165

  5. Repair of radiation damage in mammalian cells

    SciTech Connect

    Setlow, R.B.

    1981-01-01

    The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis.

  6. Angiogenesis is inhibitory for mammalian digit regeneration

    PubMed Central

    Yu, Ling; Yan, Mingquan; Simkin, Jennifer; Ketcham, Paulina D.; Leininger, Eric; Han, Manjong

    2014-01-01

    Abstract The regenerating mouse digit tip is a unique model for investigating blastema formation and epimorphic regeneration in mammals. The blastema is characteristically avascular and we previously reported that blastema expression of a known anti‐angiogenic factor gene, Pedf, correlated with a successful regenerative response (Yu, L., Han, M., Yan, M., Lee, E. C., Lee, J. & Muneoka, K. (2010). BMP signaling induces digit regeneration in neonatal mice. Development, 137, 551–559). Here we show that during regeneration Vegfa transcripts are not detected in the blastema but are expressed at the onset of differentiation. Treating the amputation wound with vascular endothelial growth factor enhances angiogenesis but inhibits regeneration. We next tested bone morphogenetic protein 9 (BMP9), another known mediator of angiogenesis, and found that BMP9 is also a potent inhibitor of digit tip regeneration. BMP9 induces Vegfa expression in the digit stump suggesting that regenerative failure is mediated by enhanced angiogenesis. Finally, we show that BMP9 inhibition of regeneration is completely rescued by treatment with pigment epithelium‐derived factor. These studies show that precocious angiogenesis is inhibitory for regeneration, and provide compelling evidence that the regulation of angiogenesis is a critical factor in designing therapies aimed at stimulating mammalian regeneration.

  7. The Nucleosome Map of the Mammalian Liver

    PubMed Central

    Li, Zhaoyu; Schug, Jonathan; Tuteja, Geetu; White, Peter; Kaestner, Klaus H.

    2011-01-01

    Mammalian genomes contain billions of basepairs of DNA that must be highly compacted as chromatin to fit into the nano-scale of the nucleus, but yet be accessible to allow for transcription to occur. Binding to nucleosomal DNA is critical for ‘pioneer’ transcription factors such as the winged helix transcription factors Foxa1 and Foxa2 to regulate chromatin structure and gene activation. Here we report the genome-wide map of nucleosome positions in the mouse liver, with emphasis on transcriptional start sites, CpG islands, Foxa2 binding sites, and their correlation with gene expression. Despite the heterogeneity of liver tissue, we could clearly discern the nucleosome pattern of the predominant liver cell, the hepatocyte. By analyzing nucleosome occupancy and the distributions of heterochromatin protein 1 (Hp1), CBP (also known as Crebbp), and p300 (Ep300) in Foxa1/2-deficient livers we find, surprisingly, that the maintenance of nucleosome position and chromatin structure surrounding Foxa2 binding sites is independent of Foxa1/2. PMID:21623366

  8. Functions of miRNAs during Mammalian Heart Development

    PubMed Central

    Yan, Shun; Jiao, Kai

    2016-01-01

    MicroRNAs (miRNAs) play essential roles during mammalian heart development and have emerged as attractive therapeutic targets for cardiovascular diseases. The mammalian embryonic heart is mainly derived from four major cell types during development. These include cardiomyocytes, endocardial cells, epicardial cells, and neural crest cells. Recent data have identified various miRNAs as critical regulators of the proper differentiation, proliferation, and survival of these cell types. In this review, we briefly introduce the contemporary understanding of mammalian cardiac development. We also focus on recent developments in the field of cardiac miRNAs and their functions during the development of different cell types. PMID:27213371

  9. Fishing for mammalian paradigms in the teleost immune system

    PubMed Central

    Sunyer, J Oriol

    2013-01-01

    Recent years have witnessed a renaissance in the study of fish immune systems. Such studies have greatly expanded the knowledge of the evolution and diversification of vertebrate immune systems. Several findings in those studies have overturned old paradigms about the immune system and led to the discovery of novel aspects of mammalian immunity. Here I focus on how findings pertaining to immunity in teleost (bony) fish have led to major new insights about mammalian B cell function in innate and adaptive immunity. Additionally, I illustrate how the discovery of the most ancient mucosal immunoglobulin described thus far will help resolve unsettled paradigms of mammalian mucosal immunity. PMID:23507645

  10. Training rats to voluntarily dive underwater: investigations of the mammalian diving response.

    PubMed

    McCulloch, Paul F

    2014-01-01

    Underwater submergence produces autonomic changes that are observed in virtually all diving animals. This reflexly-induced response consists of apnea, a parasympathetically-induced bradycardia and a sympathetically-induced alteration of vascular resistance that maintains blood flow to the heart, brain and exercising muscles. While many of the metabolic and cardiorespiratory aspects of the diving response have been studied in marine animals, investigations of the central integrative aspects of this brainstem reflex have been relatively lacking. Because the physiology and neuroanatomy of the rat are well characterized, the rat can be used to help ascertain the central pathways of the mammalian diving response. Detailed instructions are provided on how to train rats to swim and voluntarily dive underwater through a 5 m long Plexiglas maze. Considerations regarding tank design and procedure room requirements are also given. The behavioral training is conducted in such a way as to reduce the stressfulness that could otherwise be associated with forced underwater submergence, thus minimizing activation of central stress pathways. The training procedures are not technically difficult, but they can be time-consuming. Since behavioral training of animals can only provide a model to be used with other experimental techniques, examples of how voluntarily diving rats have been used in conjunction with other physiological and neuroanatomical research techniques, and how the basic training procedures may need to be modified to accommodate these techniques, are also provided. These experiments show that voluntarily diving rats exhibit the same cardiorespiratory changes typically seen in other diving animals. The ease with which rats can be trained to voluntarily dive underwater, and the already available data from rats collected in other neurophysiological studies, makes voluntarily diving rats a good behavioral model to be used in studies investigating the central aspects of the

  11. HYPOTHYRODISM INDUCED BY EARLY POSTNATAL EXPOSURE TO PROPYLTHIOURACIL IMPAIRS SYNAPTIC TRANSMISSION IN VIVO IN THE HIPPOCAMPUS OF THE ADULT RAT.

    EPA Science Inventory

    Thyroid hormones are essential for maturation and function of the mammalian central nervous system. Severe congenital hypothyroidism results in irreversible structural damage and mental retardation in children. Although a variety of environmental contaminants have been demonstrat...

  12. Urinary tract infection - adults

    MedlinePlus

    Bladder infection - adults; UTI - adults; Cystitis - bacterial - adults; Pyelonephritis - adults; Kidney infection - adults ... to the hospital if you: Are an older adult Have kidney stones or changes in the anatomy ...

  13. Neuroanatomy: connectome connects fly and mammalian brain networks.

    PubMed

    Kaiser, Marcus

    2015-05-18

    A recent study shows that brain connectivity in Drosophila melanogaster follows a small-world, modular and rich-club organisation that facilitates information processing. This organisation shows a striking similarity with the mammalian brain. PMID:25989081

  14. GENE EXPRESSION IN PRE-IMPLANTATION MAMMALIAN EMBRYOS

    EPA Science Inventory

    The pre-implantation mammalian embryo is initially under the control of maternal informational macromolecules that are accumulated during oogenesis. ubsequently, the genetic program of development becomes dependent upon new transcription derived from activation of the embryonic g...

  15. Profiling Signaling Peptides in Single Mammalian Cells Using Mass Spectrometry

    PubMed Central

    Rubakhin, Stanislav S.; Churchill, James D.; Greenough, William T.; Sweedler, Jonathan V.

    2008-01-01

    The peptide content of individual mammalian cells is profiled using matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry. Both enzymatic and non-enzymatic procedures, including a glycerol cell stabilization method, are reported for the isolation of individual mammalian cells in a manner compatible with MALDI MS measurements. Guided microdeposition of MALDI matrix allows samples to be created with suitable analyte-to-matrix ratios. More than fifteen peptides are observed in individual rat intermediate pituitary cells. The combination of accurate mass data, expected cleavages by proteolytic enzymes, and post-source decay sequencing allows identification of fourteen of these peptides as pro-opiomelanocortin prohormone-derived molecules. These protocols permit the classification of individual mammalian cells by peptide profile, the elucidation of cell-specific prohormone processing, and the discovery of new signaling peptides on a cell-to-cell basis in a wide variety of mammalian cell types. PMID:17037931

  16. Cell lineage in mammalian craniofacial mesenchyme.

    PubMed

    Yoshida, Toshiyuki; Vivatbutsiri, Philaiporn; Morriss-Kay, Gillian; Saga, Yumiko; Iseki, Sachiko

    2008-01-01

    We have analysed the contributions of neural crest and mesoderm to mammalian craniofacial mesenchyme and its derivatives by cell lineage tracing experiments in mouse embryos, using the permanent genetic markers Wnt1-cre for neural crest and Mesp1-cre for mesoderm, combined with the Rosa26 reporter. At the end of neural crest cell migration (E9.5) the two patterns are reciprocal, with a mutual boundary just posterior to the eye. Mesodermal cells expressing endothelial markers (angioblasts) are found not to respect this boundary; they are associated with the migrating neural crest from the 5-somite stage, and by E9.5 they form a pre-endothelial meshwork throughout the cranial mesenchyme. Mesodermal cells of the myogenic lineage also migrate with neural crest cells, as the branchial arches form. By E17.5 the neural crest-mesoderm boundary in the subectodermal mesenchyme becomes out of register with that of the underlying skeletogenic layer, which is between the frontal and parietal bones. At E13.5 the primordia of these bones lie basolateral to the brain, extending towards the vertex of the skull during the following 4-5 days. We used DiI labelling of the bone primordia in ex-utero E13.5 embryos to distinguish between two possibilities for the origin of the frontal and parietal bones: (1) recruitment from adjacent connective tissue or (2) proliferation of the original primordia. The results clearly demonstrated that the bone primordia extend vertically by intrinsic growth, without detectable recruitment of adjacent mesenchymal cells. PMID:18617001

  17. Assays for mammalian tyrosinase: a comparative study

    SciTech Connect

    Jara, J.R.; Solano, F.; Lozano, J.A.

    1988-01-01

    This work describes a comparative study of the tyrosinase activity determined using three methods which are the most extensively employed; two radiometric assays using L-tyrosine as substrate (tyrosine hydroxylase and melanin formation activities) and one spectrophotometric assay using L-dopa (dopa oxidase activity). The three methods were simultaneously employed to measure the activities of the soluble, melanosomal, and microsomal tyrosinase isozymes from Harding-Passey mouse melanoma through their purification processes. The aim of this study was to find any correlation among the tyrosinase activities measured by the three different assays and to determine whether that correlation varied with the isozyme and its degree of purification. The results show that mammalian tyrosinase has a greater turnover number for L-dopa than for L-tyrosine. Thus, enzyme activity, expressed as mumol of substrate transformed per min, is higher in assays using L-dopa as substrate than those using L-tyrosine. Moreover, the percentage of hydroxylated L-tyrosine that is converted into melanin is low and is affected by several factors, apparently decreasing the tyrosinase activity measured by the melanin formation assay. Bearing these considerations in mind, average interassay factors are proposed. Their values are 10 to transform melanin formation into tyrosine hydroxylase activity, 100 to transform tyrosine hydroxylase into dopa oxidase activity, and 1,000 to transform melanin formation into dopa oxidase activity. Variations in these values due to the presence in the tyrosinase preparations of either inhibitors or regulatory factors in melanogenesis independent of tyrosinase are also discussed.

  18. Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses.

    PubMed

    Rebollo, Rita; Mager, Dixie L

    2016-01-01

    Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone-repressive modifications and DNA methylation. Here we describe a common method used in our laboratory to detect, quantify, and compare mammalian endogenous retrovirus DNA methylation. More specifically we describe methylated DNA immunoprecipitation (MeDIP) followed by quantitative PCR. PMID:26895065

  19. Hypergravity signal transduction and gene expression in cultured mammalian cells

    NASA Technical Reports Server (NTRS)

    Kumei, Y.; Whitson, P. A.

    1994-01-01

    A number of studies have been conducted during space flight and with clinostats and centrifuges, suggesting that gravity effects the proliferation and differentiation of mammalian cells in vitro. However, little is known about the mechanisms by which mammalian cells respond to changes in gravitational stress. This paper summarizes studies designed to clarify the effects of hypergravity on the cultured human HeLa cells and to investigate the mechanism of hypergravity signal transduction in these cells.

  20. Multi-cellular, three-dimensional living mammalian tissue

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J. (Inventor); Wolf, David A. (Inventor)

    1994-01-01

    The present invention relates to a multicellular, three-dimensional, living mammalian tissue. The tissue is produced by a co-culture process wherein two distinct types of mammalian cells are co-cultured in a rotating bioreactor which is completely filled with culture media and cell attachment substrates. As the size of the tissue assemblies formed on the attachment substrates changes, the rotation of the bioreactor is adjusted accordingly.