High-frequency oscillations in human and monkey neocortex during the wake–sleep cycle

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Le Van Quyen, Michel; Muller, Lyle E.; Telenczuk, Bartosz; Halgren, Eric; Cash, Sydney; Hatsopoulos, Nicholas G.; Dehghani, Nima; Destexhe, Alain

2016-01-01

Beta (β)- and gamma (γ)-oscillations are present in different cortical areas and are thought to be inhibition-driven, but it is not known if these properties also apply to γ-oscillations in humans. Here, we analyze such oscillations in high-density microelectrode array recordings in human and monkey during the wake–sleep cycle. In these recordings, units were classified as excitatory and inhibitory cells. We find that γ-oscillations in human and β-oscillations in monkey are characterized by a strong implication of inhibitory neurons, both in terms of their firing rate and their phasic firing with the oscillation cycle. The β- and γ-waves systematically propagate across the array, with similar velocities, during both wake and sleep. However, only in slow-wave sleep (SWS) β- and γ-oscillations are associated with highly coherent and functional interactions across several millimeters of the neocortex. This interaction is specifically pronounced between inhibitory cells. These results suggest that inhibitory cells are dominantly involved in the genesis of β- and γ-oscillations, as well as in the organization of their large-scale coherence in the awake and sleeping brain. The highest oscillation coherence found during SWS suggests that fast oscillations implement a highly coherent reactivation of wake patterns that may support memory consolidation during SWS. PMID:27482084

Quantitative relationships in delphinid neocortex

DEFF Research Database (Denmark)

Mortensen, Heidi S.; Pakkenberg, Bente; Dam, Maria

2014-01-01

total number of brain cells in cetaceans, and even fewer have used unbiased counting methods. In this study, using stereological methods, we estimated the total number of cells in the neocortex of the long-finned pilot whale (Globicephala melas) brain. For the first time, we show that a species...

Long-range GABAergic connections distributed throughout the neocortex and their possible function

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Nobuaki eTamamaki

2010-12-01

Full Text Available Features and functions of long range GABAergic projection neurons in the developing cerebral cortex have been reported previously, although until now their significance in the adult cerebral cortex has remained uncertain. The septo-hippocampal circuit is one exception – in this system, long range mature GABAergic projection neurons have been well analyzed and their contribution to the generation of theta-oscillatory behavior in the hippocampus has been documented. To have a clue to the function of the GABAergic projection neurons in the neocortex, we view the long range GABAergic projections those participating in the cortico-cortical, cortico-fugal, and afferent projections in the cerebral cortex. Then, we consider the possibility that the GABAergic projection neurons are involved in the generation, modification, and/or synchronization of oscillations in mature neocortical neuron activity. When markers that identify the GABAergic projection neurons are examined in anatomical and developmental studies, it is clear that neuronal NO synthetase (nNOS-immunoreactivity can readily identify GABAergic projection fibers (i.e. those longer than 1.5 mm. To elucidate the role of the GABAergic projection neurons in the neocortex, it will be necessary to clarify the network constructed by nNOS-positive GABAergic projection neurons and their postsynaptic targets. Thus, our long-range goals will be to label and manipulate (including deleting the GABAergic projection neurons using genetic tools driven by a nNOS promoter. We recognize that this may be a complex endeavor, as most excitatory neurons in the murine neocortex express nNOS transiently. Nevertheless, additional studies characterizing long range GABAergic projection neurons will have great value to the overall understanding of mature cortical function.

The distribution of chandelier cell axon terminals that express the GABA plasma membrane transporter GAT-1 in the human neocortex.

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Inda, M C; Defelipe, J; Muñoz, A

2007-09-01

Chandelier cells represent a unique type of cortical GABAergic interneuron whose axon terminals (Ch-terminals) form synapses exclusively with the axon initial segments of pyramidal cells. In this study, we have used immunocytochemistry for the high-affinity plasma membrane transporter-1 (GAT-1) to analyze the distribution and density of Ch-terminals in various cytoarchitectonic and functional areas of the human neocortex. The lowest density of GAT-1-immuoreactive (-ir) Ch-terminals was detected in the primary and secondary visual (areas 17 and 18) and in the somatosensory areas (areas 3b and 1). In contrast, an intermediate density was observed in the motor area 4 and the associative frontolateral areas 45 and 46, whereas the associative frontolateral areas 9 and 10, frontal orbitary areas 11, 12, 13, 14, and 47, associative temporal areas 20, 21, 22, and 38, and cingulate areas 24 and 32 displayed the highest density of GAT-1-ir Ch-terminals. Despite these differences, the laminar distribution of GAT-1-ir Ch-terminals was similar in most cortical areas. Hence, the highest density of this transporter was observed in layer II, followed by layers III, V, VI, and IV. In most cortical areas, the density of GAT-1-ir Ch-terminals was positively correlated with the neuronal density, although a negative correlation was detected in layer III across all cortical areas. These results indicate that there are substantial differences in the distribution and density of GAT-1-ir Ch-terminals between areas and layers of the human neocortex. These differences might be related to the different functional attributes of the cortical regions examined.

Overproduction of Upper-Layer Neurons in the Neocortex Leads to Autism-like Features in Mice

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Wei-Qun Fang

2014-12-01

Full Text Available Summary: The functional integrity of the neocortex depends upon proper numbers of excitatory and inhibitory neurons; however, the consequences of dysregulated neuronal production during the development of the neocortex are unclear. As excess cortical neurons are linked to the neurodevelopmental disorder autism, we investigated whether the overproduction of neurons leads to neocortical malformation and malfunction in mice. We experimentally increased the number of pyramidal neurons in the upper neocortical layers by using the small molecule XAV939 to expand the intermediate progenitor population. The resultant overpopulation of neurons perturbs development of dendrites and spines of excitatory neurons and alters the laminar distribution of interneurons. Furthermore, these phenotypic changes are accompanied by dysregulated excitatory and inhibitory synaptic connection and balance. Importantly, these mice exhibit behavioral abnormalities resembling those of human autism. Thus, our findings collectively suggest a causal relationship between neuronal overproduction and autism-like features, providing developmental insights into the etiology of autism. : Fang et al. generated a mouse model with excessive excitatory neurons in the neocortex by manipulating embryonic neurogenesis. Overproduction of neurons results in autism-like anatomical and behavioral features. These findings suggest a causal relationship between overproduction of neurons and cortical malfunction and provide developmental insights into the etiology of autism.

An empirical analysis of the precision of estimating the numbers of neurons and glia in human neocortex using a fractionator-design with sub-sampling

DEFF Research Database (Denmark)

Lyck, L.; Santamaria, I.D.; Pakkenberg, B.

2009-01-01

Improving histomorphometric analysis of the human neocortex by combining stereological cell counting with immunchistochemical visualisation of specific neuronal and glial cell populations is a methodological challenge. To enable standardized immunohistochemical staining, the amount of brain tissue...... at each level of sampling was determined empirically. The methodology was tested in three brains analysing the contribution of the multi-step sampling procedure to the precision on the estimated total numbers of immunohistochemically defined NeuN expressing (NeuN(+)) neurons and CD45(+) microglia...

Cytoarchitecture in cultured rat neocortex explants

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de Jong, B. M.; Ruijter, J. M.; Romijn, H. J.

1988-01-01

Neocortex explants obtained from 6-day-old rat pups and cultured in a serum-free medium from 5 hr to 13 days in vitro (DIV) show preservation of cytoarchitectural characteristics. Major changes in the size of the explants and their layers occur during the first 2 DIV. A radial arrangement of neurons

The emergence of mind and emotion in the evolution of neocortex.

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Freeman, Walter J

2011-01-01

The most deeply transformative concept for the growth of 21st Century psychiatry is the constellation of the chaotic dynamics of the brain. Brains are no longer seen as rational systems that are plagued with emotional disorders reflecting primitives inherited from our animal ancestors. Brains are dynamical systems that continually create patterns by acting intentionally into the environment and shaping themselves in accord with the sensory consequences of their intended actions. Emotions are now seen not as reversions to animal behaviors but as the sources of force and energy that brains require for the actions they take to understand the world and themselves. Humans are unique in experiencing consciousness of their own actions, which they experience as conscience: guilt, shame, pride and joy. Chaotic brain dynamics strives always for unity and harmony, but as a necessary condition for adaptation to a changing world, it repeatedly lapses into disorder. The successes are seen in the normal unity of consciousness; the failures are seen in the disorders that we rightly label the schizophrenias and the less severe character disorders. The foundation for healthy unity is revealed by studies in the evolution of brains, in particular the way in which neocortex of mammals emerged from the primitive allocortex of reptiles. The amazing facts of brain dynamics are now falling into several places. The power-law connectivity of cortex supports the scale-free dynamics of the global workspace in brains ranging from mouse to whale. That dynamics in humans holds the secrets of speech and symbol utilization. By recursive interactions in vast areas of human neocortex the scale-free connectivity supports our unified consciousness. Here in this dynamics are to be sought the keys to understanding and treating the disorders that uniquely plague the human mind.

High Bandwidth Synaptic Communication and Frequency Tracking in Human Neocortex

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G. Testa-Silva (Guilherme); M.B. Verhoog (Matthijs); D. Linaro (Daniele); C.P.J. de Kock (Christiaan); J.C. Baayen; R.M. Meredith (Rhiannon); C.I. de Zeeuw (Chris); M. Giugliano (Michele); H.D. Mansvelder (Huibert)

2014-01-01

textabstractNeuronal firing, synaptic transmission, and its plasticity form the building blocks for processing and storage of information in the brain. It is unknown whether adult human synapses are more efficient in transferring information between neurons than rodent synapses. To test this, we

THIP, a hypnotic and antinociceptive drug, enhances a tonic GABAA receptor mediated conductance in mouse neocortex

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Drasbek, Kim Ryun; Jensen, Kimmo

2006-01-01

its cellular actions in the neocortex are uncertain, we studied the effects of THIP on neurons in slices of frontoparietal neocortex of 13- to 19-day-old (P13-19) mice. Using whole-cell patch-clamp recordings, we found that the clinically relevant THIP concentration of 1 μM induced a robust tonic GABA...... suggest that THIP activates an extrasynaptic GABA(A) receptor-mediated conductance in the neocortex, which may alter the cortical network activity....

High bandwidth synaptic communication and frequency tracking in human neocortex

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Testa-Silva, Guilherme; Verhoog, Matthijs B; Linaro, Daniele; de Kock, Christiaan P J; Baayen, Johannes C; Meredith, Rhiannon M; De Zeeuw, Chris I; Giugliano, Michele; Mansvelder, Huibert D

2014-01-01

Neuronal firing, synaptic transmission, and its plasticity form the building blocks for processing and storage of information in the brain. It is unknown whether adult human synapses are more efficient in transferring information between neurons than rodent synapses. To test this, we recorded from

High bandwidth synaptic communication and frequency tracking in human neocortex.

NARCIS (Netherlands)

Testa-Silva, G.; Verhoog, M.B.; Linaro, D.; de Kock, C.P.J.; Baayen, J.C.; Meredith, R.M.; Zeeuw, C.I.; Giugliano, M.; Mansvelder, H.D.

2014-01-01

Neuronal firing, synaptic transmission, and its plasticity form the building blocks for processing and storage of information in the brain. It is unknown whether adult human synapses are more efficient in transferring information between neurons than rodent synapses. To test this, we recorded from

The evolution of neocortex in primates.

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Kaas, Jon H

2012-01-01

We can learn about the evolution of neocortex in primates through comparative studies of cortical organization in primates and those mammals that are the closest living relatives of primates, in conjunction with brain features revealed by the skull endocasts of fossil archaic primates. Such studies suggest that early primates had acquired a number of features of neocortex that now distinguish modern primates. Most notably, early primates had an array of new visual areas, and those visual areas widely shared with other mammals had been modified. Posterior parietal cortex was greatly expanded with sensorimotor modules for reaching, grasping, and personal defense. Motor cortex had become more specialized for hand use, and the functions of primary motor cortex were enhanced by the addition and development of premotor and cingulate motor areas. Cortical architecture became more varied, and cortical neuron populations became denser overall than in nonprimate ancestors. Primary visual cortex had the densest population of neurons, and this became more pronounced in the anthropoid radiation. Within the primate clade, considerable variability in cortical size, numbers of areas, and architecture evolved. Copyright © 2012 Elsevier B.V. All rights reserved.

Neural Progenitors in the Developing Neocortex of the Northern Tree Shrew (Tupaia belangeri Show a Closer Relationship to Gyrencephalic Primates Than to Lissencephalic Rodents

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Sebastian Römer

2018-04-01

Full Text Available The neocortex is the most complex part of the mammalian brain and as such it has undergone tremendous expansion during evolution, especially in primates. The majority of neocortical neurons originate from distinct neural stem and progenitor cells (NPCs located in the ventricular and subventricular zone (SVZ. Previous studies revealed that the SVZ thickness as well as the abundance and distribution of NPCs, especially that of basal radial glia (bRG, differ markedly between the lissencephalic rodent and gyrencephalic primate neocortex. The northern tree shrew (Tupaia belangeri is a rat-sized mammal with a high brain to body mass ratio, which stands phylogenetically mid-way between rodents and primates. Our study provides – for the first time – detailed data on the presence, abundance and distribution of bRG and other distinct NPCs in the developing neocortex of the northern tree shrew (Tupaia belangeri. We show that the developing tree shrew neocortex is characterized by an expanded SVZ, a high abundance of Pax6+ NPCs in the SVZ, and a relatively high percentage of bRG at peak of upper-layer neurogenesis. We further demonstrate that key features of tree shrew neocortex development, e.g., the presence, abundance and distribution of distinct NPCs, are closer related to those of gyrencephalic primates than to those of ferret and lissencephalic rodents. Together, our study provides novel insight into the evolution of bRG and other distinct NPCs in the neocortex development of Euarchontoglires and introduces the tree shrew as a potential novel model organism in the area of human brain development and developmental disorders.

Neocortex and allocortex respond differentially to cellular stress in vitro and aging in vivo.

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Jessica M Posimo

Full Text Available In Parkinson's and Alzheimer's diseases, the allocortex accumulates aggregated proteins such as synuclein and tau well before neocortex. We present a new high-throughput model of this topographic difference by microdissecting neocortex and allocortex from the postnatal rat and treating them in parallel fashion with toxins. Allocortical cultures were more vulnerable to low concentrations of the proteasome inhibitors MG132 and PSI but not the oxidative poison H2O2. The proteasome appeared to be more impaired in allocortex because MG132 raised ubiquitin-conjugated proteins and lowered proteasome activity in allocortex more than neocortex. Allocortex cultures were more vulnerable to MG132 despite greater MG132-induced rises in heat shock protein 70, heme oxygenase 1, and catalase. Proteasome subunits PA700 and PA28 were also higher in allocortex cultures, suggesting compensatory adaptations to greater proteasome impairment. Glutathione and ceruloplasmin were not robustly MG132-responsive and were basally higher in neocortical cultures. Notably, neocortex cultures became as vulnerable to MG132 as allocortex when glutathione synthesis or autophagic defenses were inhibited. Conversely, the glutathione precursor N-acetyl cysteine rendered allocortex resilient to MG132. Glutathione and ceruloplasmin levels were then examined in vivo as a function of age because aging is a natural model of proteasome inhibition and oxidative stress. Allocortical glutathione levels rose linearly with age but were similar to neocortex in whole tissue lysates. In contrast, ceruloplasmin levels were strikingly higher in neocortex at all ages and rose linearly until middle age. PA28 levels rose with age and were higher in allocortex in vivo, also paralleling in vitro data. These neo- and allocortical differences have implications for the many studies that treat the telencephalic mantle as a single unit. Our observations suggest that the topographic progression of protein

Abundant Occurrence of Basal Radial Glia in the Subventricular Zone of Embryonic Neocortex of a Lissencephalic Primate, the Common Marmoset Callithrix jacchus

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Kelava, Iva; Reillo, Isabel; Murayama, Ayako Y.; Kalinka, Alex T.; Stenzel, Denise; Tomancak, Pavel; Matsuzaki, Fumio; Lebrand, Cécile; Sasaki, Erika; Schwamborn, Jens C.; Okano, Hideyuki; Borrell, Víctor

2012-01-01

Subventricular zone (SVZ) progenitors are a hallmark of the developing neocortex. Recent studies described a novel type of SVZ progenitor that retains a basal process at mitosis, sustains expression of radial glial markers, and is capable of self-renewal. These progenitors, referred to here as basal radial glia (bRG), occur at high relative abundance in the SVZ of gyrencephalic primates (human) and nonprimates (ferret) but not lissencephalic rodents (mouse). Here, we analyzed the occurrence of bRG cells in the embryonic neocortex of the common marmoset Callithrix jacchus, a near-lissencephalic primate. bRG cells, expressing Pax6, Sox2 (but not Tbr2), glutamate aspartate transporter, and glial fibrillary acidic protein and retaining a basal process at mitosis, occur at similar relative abundance in the marmoset SVZ as in human and ferret. The proportion of progenitors in M-phase was lower in embryonic marmoset than developing ferret neocortex, raising the possibility of a longer cell cycle. Fitting the gyrification indices of 26 anthropoid species to an evolutionary model suggested that the marmoset evolved from a gyrencephalic ancestor. Our results suggest that a high relative abundance of bRG cells may be necessary, but is not sufficient, for gyrencephaly and that the marmoset's lissencephaly evolved secondarily by changing progenitor parameters other than progenitor type. PMID:22114084

Degenerative changes and cell death in long-living homo- and heterotopic transplants from embryonic germ layers of rat neocortex.

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Petrova, E S; Otellin, V A

2003-09-01

Morphological study of allotransplants of rat embryonic neocortex 14-18 months after transplantation into the neocortex, lateral cerebral ventricle, and sciatic nerve of adult animals revealed death of nerve and glial cells in the delayed postoperation period independently on the site of transplantation. After heterotopic transplantation the count of degenerated neurons was 2 times higher that after homotopic transplantation. In heterotopic transplants a considerable number of grafted neurons underwent reversible and irreversible degenerative changes accompanied by their premature aging. Neuronal death is probably determined by insufficiency of trophic influence from afferent structures and target tissues. We hypothesized that antiapoptotic preparations can be used for prevention of transplanted cell death. It was also found that degeneration of neurons was associated with impaired vascularization of transplants and pronounced immune reaction of the recipient in late posttransplantation period. Transplantation of embryonic brain structures can serve as a model system in studies concerning involutive and pathological processes in the central nervous system and in the search for factors improving survival of neurons.

Nogo-receptor gene activity: cellular localization and developmental regulation of mRNA in mice and humans.

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Josephson, Anna; Trifunovski, Alexandra; Widmer, Hans Ruedi; Widenfalk, Johan; Olson, Lars; Spenger, Christian

2002-11-18

Nogo (reticulon-4) is a myelin-associated protein that is expressed in three different splice variants, Nogo-A, Nogo-B, and Nogo-C. Nogo-A inhibits neurite regeneration in the central nervous system. Messenger RNA encoding Nogo is expressed in oligodendrocytes and central and peripheral neurons, but not in astrocytes or Schwann cells. Nogo is a transmembraneous protein; the extracellular domain is termed Nogo-66, and a Nogo-66-receptor (Nogo-R) has been identified. We performed in situ hybridization in human and mouse nervous tissues to map the cellular distribution of Nogo-R gene activity patterns in fetal and adult human spinal cord and sensory ganglia, adult human brain, and the nervous systems of developing and adult mice. In the human fetus Nogo-R was transcribed in the ventral horn of the spinal cord and in dorsal root ganglia. In adult human tissues Nogo-R gene activity was found in neocortex, hippocampus, amygdala, and a subset of large and medium-sized neurons of the dorsal root ganglia. Nogo-R mRNA was not expressed in the adult human spinal cord at detectable levels. In the fetal mouse, Nogo-R was diffusely expressed in brain, brainstem, trigeminal ganglion, spinal cord, and dorsal root ganglia at all stages. In the adult mouse strong Nogo-R mRNA expression was found in neurons in neocortex, hippocampus, amygdala, habenula, thalamic nuclei, brainstem, the granular cell layer of cerebellum, and the mitral cell layer of the olfactory bulb. Neurons in the adult mouse striatum, the medial septal nucleus, and spinal cord did not express Nogo-R mRNA at detectable levels. In summary, Nogo-66-R mRNA expression in humans and mice was observed in neurons of the developing nervous system Expression was downregulated in the adult spinal cord of both species, and specific expression patterns were seen in the adult brain. Copyright 2002 Wiley-Liss, Inc.

Laminar and Temporal Expression Dynamics of Coding and Noncoding RNAs in the Mouse Neocortex

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Sofia Fertuzinhos

2014-03-01

Full Text Available The hallmark of the cerebral neocortex is its organization into six layers, each containing a characteristic set of cell types and synaptic connections. The transcriptional events involved in laminar development and function still remain elusive. Here, we employed deep sequencing of mRNA and small RNA species to gain insights into transcriptional differences among layers and their temporal dynamics during postnatal development of the mouse primary somatosensory neocortex. We identify a number of coding and noncoding transcripts with specific spatiotemporal expression and splicing patterns. We also identify signature trajectories and gene coexpression networks associated with distinct biological processes and transcriptional overlap between these processes. Finally, we provide data that allow the study of potential miRNA and mRNA interactions. Overall, this study provides an integrated view of the laminar and temporal expression dynamics of coding and noncoding transcripts in the mouse neocortex and a resource for studies of neurodevelopment and transcriptome.

Human-Specific Cortical Synaptic Connections and Their Plasticity: Is That What Makes Us Human?

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Joana Lourenço

2017-01-01

Full Text Available One outstanding difference between Homo sapiens and other mammals is the ability to perform highly complex cognitive tasks and behaviors, such as language, abstract thinking, and cultural diversity. How is this accomplished? According to one prominent theory, cognitive complexity is proportional to the repetition of specific computational modules over a large surface expansion of the cerebral cortex (neocortex. However, the human neocortex was shown to also possess unique features at the cellular and synaptic levels, raising the possibility that expanding the computational module is not the only mechanism underlying complex thinking. In a study published in PLOS Biology, Szegedi and colleagues analyzed a specific cortical circuit from live postoperative human tissue, showing that human-specific, very powerful excitatory connections between principal pyramidal neurons and inhibitory neurons are highly plastic. This suggests that exclusive plasticity of specific microcircuits might be considered among the mechanisms endowing the human neocortex with the ability to perform highly complex cognitive tasks.

The building of the neocortex with non-hyperpolarizing neurotransmitters.

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Ascenzi, Matteo; Bony, Guillaume

2017-09-01

The development of the neocortex requires the synergic action of several secreted molecules to achieve the right amount of proliferation, differentiation, and migration of neural cells. Neurons are well known to release neurotransmitters (NTs) in adult and a growing body of evidences describes the presence of NTs already in the embryonic brain, long before the generation of synapses. NTs are classified as inhibitory or excitatory based on the physiological responses of the target neuron. However, this view is challenged by the fact that glycine and GABA NTs are excitatory during development. Many reviews have described the role of nonhyperpolarizing GABA at this stage. Nevertheless, a global consideration of the inhibitory neurotransmitters and their downstream signaling during the embryonic cortical development is still needed. For example, taurine, the most abundant neurotransmitter during development is poorly studied regarding its role during cortical development. In the light of recent discoveries, we will discuss the functions of glycine, GABA, and taurine during embryonic cortical development with an emphasis on their downstream signaling. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1023-1037, 2017. © 2017 Wiley Periodicals, Inc.

GABA-mediated synchronization in the human neocortex: elevations in extracellular potassium and presynaptic mechanisms.

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Louvel, J; Papatheodoropoulos, C; Siniscalchi, A; Kurcewicz, I; Pumain, R; Devaux, B; Turak, B; Esposito, V; Villemeure, J G; Avoli, M

2001-01-01

Field potential and extracellular [K(+)] ([K(+)](o)) recordings were made in the human neocortex in an in vitro slice preparation to study the synchronous activity that occurs in the presence of 4-aminopyridine (50 microM) and ionotropic excitatory amino acid receptor antagonists. Under these experimental conditions, negative or negative-positive field potentials accompanied by rises in [K(+)](o) (up to 4.1 mM from a baseline of 3.25 mM) occurred spontaneously at intervals of 3-27 s. Both field potentials and [K(+)](o) elevations were largest at approximately 1000 microm from the pia. Similar events were induced by neocortical electrical stimuli. Application of medium containing low [Ca(2+)]/high [Mg(2+)] (n=3 slices), antagonism of the GABA(A) receptor (n=7) or mu-opioid receptor activation (n=4) abolished these events. Hence, they represented network, GABA-mediated potentials mainly reflecting the activation of type A receptors following GABA release from interneurons. The GABA(B) receptor agonist baclofen (10-100 microM, n=11) reduced and abolished the GABA-mediated potentials (ID(50)=18 microM). Baclofen effects were antagonized by the GABA(B) receptor antagonist CGP 35348 (0.1-1 mM, n=6; ID(50)=0.19 mM). CGP 38345 application to control medium increased the amplitude of the GABA-mediated potentials and the concomitant [K(+)](o) rises without modifying their rate of occurrence. The GABA-mediated potentials were not influenced by the broad-spectrum metabotropic glutamate agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (100 microM, n=10), but decreased in rate with the group I receptor agonist (S)-3,5-dihydroxyphenylglycine (10-100 microM, n=9). Our data indicate that human neocortical networks challenged with 4-aminopyridine generate glutamatergic-independent, GABA-mediated potentials that are modulated by mu-opioid and GABA(B) receptors presumably located on interneuron terminals. These events are associated with [K(+)](o) elevations that may

Alzheimer's-type neuropathology in the precuneus is not increased relative to other areas of neocortex across a range of cognitive impairment.

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Nelson, Peter T; Abner, Erin L; Scheff, Stephen W; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Patel, Ela; Markesbery, William R

2009-02-06

We studied Alzheimer's disease (AD) pathology in the precuneus and surrounding brain areas. Anatomically, the precuneus corresponds to the medial portion of human cerebral cortical Brodmann Area 7. This study utilized patients from the University of Kentucky Alzheimer's Disease Center autopsy cohort. Data from 47 brains were used comprising patients of differing antemortem cognitive impairment severities, each with longitudinal clinical data and extensive neuropathological data. We assessed whether the precuneus and surrounding areas are differentially vulnerable to AD-type pathological lesions (diffuse amyloid plaques, neuritic amyloid plaques, and neurofibrillary tangles). Eleven areas of brain were evaluated for each case: amygdala, hippocampal CA1, subiculum, entorhinal cortex, frontal cortex, superior and middle temporal gyri, inferior parietal lobule, occipital cortex, posterior cingulate gyrus, Brodmann Area 31, and the precuneus proper. Like other areas of neocortex, the precuneus demonstrated increased diffuse and neuritic amyloid plaques early in the evolution in AD, and increased neurofibrillary tangles late in AD. Correcting for the antemortem cognitive status of the patients, there was no evidence of an increase in the density of AD-type pathology in the precuneus or neighboring areas relative to other areas of cerebral neocortex. Our results are not consistent with the idea that the precuneus is involved in a special way with plaques or tangles relative to other areas of neocortex.

Selective elimination of intracortically projecting neurons of the rat neocortex by prenatal x-irradiation

International Nuclear Information System (INIS)

Jensen, K.F.

1981-01-01

The development of new racing methods has suggested that there are species differences in the extent of the contribution of the different layers of the neocortex to the callosal projection. The present investigation has utilized prenatal x-irradiation to selectively eliminate the late forming neurons of the supragranular layers of the rat neocortex. The reduction in the neuronal population of the supragranular layers closely parallels the reduction in the corpus callosum. These results indicate that the primary source of neurons of the callosal projection, are the late forming neurons of the supragranular layers. Thus, the current results suggest that low dose prenatal x-irradiation may be used to evaluate important developmental events in the formation of neocortical circuitry

Subtypes of GABAergic neurons project axons in the neocortex

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Shigeyoshi Higo

2009-11-01

Full Text Available γ-aminobutyric acid (GABAergic neurons in the neocortex have been regarded as interneurons and speculated to modulate the activity of neurons locally. Recently, however, several experiments revealed that neuronal nitric oxide synthase (nNOS-positive GABAergic neurons project cortico-cortically with long axons. In this study, we illustrate Golgi-like images of the nNOS-positive GABAergic neurons using a nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d reaction and follow the emanating axon branches in cat brain sections. These axon branches projected cortico-cortically with other non-labeled arcuate fibers, contra-laterally via the corpus callosum and anterior commissure. The labeled fibers were not limited to the neocortex but found also in the fimbria of the hippocampus. In order to have additional information on these GABAergic neuron projections, we investigated green fluorescent protein (GFP-labeled GABAergic neurons in GAD67-Cre knock-in / GFP Cre-reporter mice. GFP-labeled axons emanate densely, especially in the fimbria, a small number in the anterior commissure, and very sparsely in the corpus callosum. These two different approaches confirm that not only nNOS-positive GABAergic neurons but also other subtypes of GABAergic neurons project long axons in the cerebral cortex and are in a position to be involved in information processing.

Comparing Epileptiform Behavior of Mesoscale Detailed Models and Population Models of Neocortex

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Visser, S.; Meijer, Hil Gaétan Ellart; Lee, Hyong C.; van Drongelen, Wim; van Putten, Michel Johannes Antonius Maria; van Gils, Stephanus A.

2010-01-01

Two models of the neocortex are developed to study normal and pathologic neuronal activity. One model contains a detailed description of a neocortical microcolumn represented by 656 neurons, including superficial and deep pyramidal cells, four types of inhibitory neurons, and realistic synaptic

Explicit logic circuits predict local properties of the neocortex's physiology and anatomy.

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Lane Yoder

Full Text Available BACKGROUND: Two previous articles proposed an explicit model of how the brain processes information by its organization of synaptic connections. The family of logic circuits was shown to generate neural correlates of complex psychophysical phenomena in different sensory systems. METHODOLOGY/PRINCIPAL FINDINGS: Here it is shown that the most cost-effective architectures for these networks produce correlates of electrophysiological brain phenomena and predict major aspects of the anatomical structure and physiological organization of the neocortex. The logic circuits are markedly efficient in several respects and provide the foundation for all of the brain's combinational processing of information. CONCLUSIONS/SIGNIFICANCE: At the local level, these networks account for much of the physical structure of the neocortex as well its organization of synaptic connections. Electronic implementations of the logic circuits may be more efficient than current electronic logic arrays in generating both Boolean and fuzzy logic.

Visualization of Functional Neuropeptide Y Receptors in the Mouse Hippocampus and Neocortex Using [35S]GTPγS Binding

DEFF Research Database (Denmark)

Elbrønd-Bek, Heidi; Gøtzsche, Casper René; Skinbjerg, Mette

2015-01-01

The peptide transmitter neuropeptide Y (NPY) has been implicated in a plethora of actions in the central nervous system, including the hippocampus and neocortex (NeoCx). Previous studies using traditional receptor autoradiography show that NPY receptor binding is altered under various pathophysio......The peptide transmitter neuropeptide Y (NPY) has been implicated in a plethora of actions in the central nervous system, including the hippocampus and neocortex (NeoCx). Previous studies using traditional receptor autoradiography show that NPY receptor binding is altered under various...

Dibucaine mitigates spreading depolarization in human neocortical slices and prevents acute dendritic injury in the ischemic rodent neocortex.

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W Christopher Risher

Full Text Available Spreading depolarizations that occur in patients with malignant stroke, subarachnoid/intracranial hemorrhage, and traumatic brain injury are known to facilitate neuronal damage in metabolically compromised brain tissue. The dramatic failure of brain ion homeostasis caused by propagating spreading depolarizations results in neuronal and astroglial swelling. In essence, swelling is the initial response and a sign of the acute neuronal injury that follows if energy deprivation is maintained. Choosing spreading depolarizations as a target for therapeutic intervention, we have used human brain slices and in vivo real-time two-photon laser scanning microscopy in the mouse neocortex to study potentially useful therapeutics against spreading depolarization-induced injury.We have shown that anoxic or terminal depolarization, a spreading depolarization wave ignited in the ischemic core where neurons cannot repolarize, can be evoked in human slices from pediatric brains during simulated ischemia induced by oxygen/glucose deprivation or by exposure to ouabain. Changes in light transmittance (LT tracked terminal depolarization in time and space. Though spreading depolarizations are notoriously difficult to block, terminal depolarization onset was delayed by dibucaine, a local amide anesthetic and sodium channel blocker. Remarkably, the occurrence of ouabain-induced terminal depolarization was delayed at a concentration of 1 µM that preserves synaptic function. Moreover, in vivo two-photon imaging in the penumbra revealed that, though spreading depolarizations did still occur, spreading depolarization-induced dendritic injury was inhibited by dibucaine administered intravenously at 2.5 mg/kg in a mouse stroke model.Dibucaine mitigated the effects of spreading depolarization at a concentration that could be well-tolerated therapeutically. Hence, dibucaine is a promising candidate to protect the brain from ischemic injury with an approach that does not rely on

The Developing, Aging Neocortex: How genetics and epigenetics influence early developmental patterning and age-related change.

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Kelly J. Huffman

2012-10-01

Full Text Available A hallmark of mammalian development is the generation of functional subdivisions within the nervous system. In humans, this regionalization creates a complex system that regulates behavior, cognition, memory and emotion. During development, specification of neocortical tissue that leads to functional sensory and motor regions results from an interplay between cortically intrinsic, molecular processes, such as gene expression, and extrinsic processes regulated by sensory input. Cortical specification in mice occurs pre- and perinatally, when gene expression is robust and various anatomical distinctions are observed alongside an emergence of physiological function. After patterning, gene expression continues to shift and axonal connections mature into an adult form. The function of adult cortical gene expression may be to maintain neocortical subdivisions that were established during early patterning. As some changes in neocortical gene expression have been observed past early development into late adulthood, gene expression may also play a role in the altered neocortical function observed in age-related cognitive decline and brain dysfunction. This review provides a discussion of how neocortical gene expression and specific patterns of neocortical sensori-motor axonal connections develop and change throughout the lifespan of the animal. We posit that a role of neocortical gene expression in neocortex is to regulate plasticity mechanisms that impact critical periods for sensory and motor plasticity in aging. We describe results from several studies in aging brain that detail changes in gene expression that may relate to microstructural changes observed in brain anatomy. We discuss the role of altered glucocorticoid signaling in age-related cognitive and functional decline, as well as how aging in the brain may result from immune system activation. We describe how caloric restriction or reduction of oxidative stress may ameliorate effects of aging

Spatial distribution of human neocortical neurons and glial cells according to sex and age measured by the saucer method

DEFF Research Database (Denmark)

Stark, Anette Kirstine; Petersen, A O; Gardi, Jonathan Eyal

2007-01-01

primary neurons in the human neocortex (divided into frontal-, temporal-, parietal- and occipital cortex) of young and old subjects free of neurological or psychological disease to test if age and gender has any influence on the cell distribution in human neocortex. Plots of the spatial distribution...

Immunocytochemical indications for neuronal co-localization of GABA and aspartate in cultured neocortex explants

NARCIS (Netherlands)

de Jong, B. M.; Ruijter, J. M.; Buijs, R. M.

1989-01-01

The application of postembedding immunocytochemistry on serial semithin plastic sections, revealed the presence of gamma-aminobutyric acid (GABA)-positive and aspartate-positive neurons in cultured neocortex explants. GABA-positive neurons were found in all layers of the cultured cortex, whereas

A procedure for culturing rat neocortex explants in a serum-free nutrient medium

NARCIS (Netherlands)

Romijn, H. J.; de Jong, B. M.; Ruijter, J. M.

1988-01-01

A procedure is described for long-term culturing of rat neocortex explants in a serum-free growth medium. Slices spanning the entire cortical depth from pial to ventricular side are prepared from 6-day-old rat pups. After preincubation in Hanks' balanced salt solution with extra glucose, the

Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun study.

Science.gov (United States)

Snowdon, D A; Tully, C L; Smith, C D; Riley, K P; Markesbery, W R

2000-04-01

Previous studies suggested that low concentrations of folate in the blood are related to poor cognitive function, dementia, and Alzheimer disease-related neurodegeneration of the brain. Our aim was to determine whether serum folate is inversely associated with the severity of atrophy of the neocortex. Nutrients, lipoproteins, and nutritional markers were measured in the blood of 30 participants in the Nun Study from one convent who later died when they were 78-101 y old (mean: 91 y). At autopsy, several neuropathologic indicators of Alzheimer disease were determined, including the degree of atrophy of 3 lobes of the neocortex (frontal, temporal, and parietal) and the number of neocortical Alzheimer disease lesions (ie, senile plaques and neurofibrillary tangles) as assessed by a neuropathologist. The correlation between serum folate and the severity of atrophy of the neocortex was -0.40 (P = 0.03). Among a subset of 15 participants with significant numbers of Alzheimer disease lesions in the neocortex, the correlation between folate and atrophy was -0.80 (P = 0.0006). Atrophy may be specific to low folate because none of the 18 other nutrients, lipoproteins, or nutritional markers measured in the blood had significant negative correlations with atrophy. Among elderly Catholic sisters who lived in one convent, ate from the same kitchen, and were highly comparable for a wide range of environmental and lifestyle factors, low serum folate was strongly associated with atrophy of the cerebral cortex. Definitive evidence for this relation and its temporal sequence awaits the findings of other studies.

Direction of Amygdala-Neocortex Interaction During Dynamic Facial Expression Processing.

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Sato, Wataru; Kochiyama, Takanori; Uono, Shota; Yoshikawa, Sakiko; Toichi, Motomi

2017-03-01

Dynamic facial expressions of emotion strongly elicit multifaceted emotional, perceptual, cognitive, and motor responses. Neuroimaging studies revealed that some subcortical (e.g., amygdala) and neocortical (e.g., superior temporal sulcus and inferior frontal gyrus) brain regions and their functional interaction were involved in processing dynamic facial expressions. However, the direction of the functional interaction between the amygdala and the neocortex remains unknown. To investigate this issue, we re-analyzed functional magnetic resonance imaging (fMRI) data from 2 studies and magnetoencephalography (MEG) data from 1 study. First, a psychophysiological interaction analysis of the fMRI data confirmed the functional interaction between the amygdala and neocortical regions. Then, dynamic causal modeling analysis was used to compare models with forward, backward, or bidirectional effective connectivity between the amygdala and neocortical networks in the fMRI and MEG data. The results consistently supported the model of effective connectivity from the amygdala to the neocortex. Further increasing time-window analysis of the MEG demonstrated that this model was valid after 200 ms from the stimulus onset. These data suggest that emotional processing in the amygdala rapidly modulates some neocortical processing, such as perception, recognition, and motor mimicry, when observing dynamic facial expressions of emotion. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A hypothesis for the evolution of the upper layers of the neocortex through co-option of the olfactory cortex developmental program.

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Federico eLuzzati

2015-05-01

Full Text Available The neocortex is unique to mammals and its evolutionary origin is still highly debated. The neocortex is generated by the dorsal pallium ventricular zone, a germinative domain that in reptiles give rise to the dorsal cortex. Whether this latter allocortical structure contains homologues of all neocortical cell types it is unclear. Recently we described a population of DCX+/Tbr1+ cells that is specifically associated with the layer II of higher order areas of both the neocortex and of the more evolutionary conserved piriform cortex. In a reptile similar cells are present in the layer II of the olfactory cortex and the DVR but not in the dorsal cortex. These data are consistent with the proposal that the reptilian dorsal cortex is homologous only to the deep layers of the neocortex while the upper layers are a mammalian innovation. Based on our observations we extended these ideas by hypothesizing that this innovation was obtained by co-opting a lateral and/or ventral pallium developmental program. Interestingly, an analysis in the Allen brain atlas revealed a striking similarity in gene expression between neocortical layers II/III and piriform cortex. We thus propose a model in which the early neocortical column originated by the superposition of the lateral olfactory and dorsal cortex. This idea is consistent with previous hypotheses that the peri-allocortex (i.e insular and perirhinal cortex may represent the more ancient neocortical part. Our model may have also interesting implications in the study of sensory processing in both neocortex and piriform cortex. The great advances in deciphering the molecular logic of the amniote pallium developmental programs will hopefully enable to directly test our hypotheses in the next future.

Visualization of cholinoceptive neurons in the rat neocortex : colocalization of muscarinic and nicotinic acetylcholine receptors

NARCIS (Netherlands)

Zee, E.A. van der; Streefland, C.; Strosberg, A.D.; Schröder, H.; Luiten, P.G.M.

The present investigation analyzes the cellular distribution of muscarinic and nicotinic acetylcholine receptors in rat neocortex, by use of monoclonal antibodies raised against purified receptor proteins. The degree of colocalization of both types of receptors was determined by way of

The fate of Nissl-stained dark neurons following traumatic brain injury in rats: difference between neocortex and hippocampus regarding survival rate.

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Ooigawa, Hidetoshi; Nawashiro, Hiroshi; Fukui, Shinji; Otani, Naoki; Osumi, Atsushi; Toyooka, Terushige; Shima, Katsuji

2006-10-01

We studied the fate of Nissl-stained dark neurons (N-DNs) following traumatic brain injury (TBI). N-DNs were investigated in the cerebral neocortex and the hippocampus using a rat lateral fluid percussion injury model. Nissl stain, acid fuchsin stain and immunohistochemistry with phosphorylated extracellular signal-regulated protein kinase (pERK) antibody were used in order to assess posttraumatic neurons. In the neocortex, the number of dead neurons at 24 h postinjury was significantly less than that of the observed N-DNs in the earlier phase. Only a few N-DNs increased their pERK immunoreactivity. On the other hand, in the hippocampus the number of dead neurons was approximately the same number as that of the N-DNs, and most N-DNs showed an increased pERK immunoreactivity. These data suggest that not all N-DNs inevitably die especially in the neocortex after TBI. The fate of N-DNs is thus considered to differ depending on brain subfields.

Combined serial analysis of gene expression and transcription factor binding site prediction identifies novel-candidate-target genes of Nr2e1 in neocortex development.

Science.gov (United States)

Schmouth, Jean-François; Arenillas, David; Corso-Díaz, Ximena; Xie, Yuan-Yun; Bohacec, Slavita; Banks, Kathleen G; Bonaguro, Russell J; Wong, Siaw H; Jones, Steven J M; Marra, Marco A; Simpson, Elizabeth M; Wasserman, Wyeth W

2015-07-24

Nr2e1 (nuclear receptor subfamily 2, group e, member 1) encodes a transcription factor important in neocortex development. Previous work has shown that nuclear receptors can have hundreds of target genes, and bind more than 300 co-interacting proteins. However, recognition of the critical role of Nr2e1 in neural stem cells and neocortex development is relatively recent, thus the molecular mechanisms involved for this nuclear receptor are only beginning to be understood. Serial analysis of gene expression (SAGE), has given researchers both qualitative and quantitative information pertaining to biological processes. Thus, in this work, six LongSAGE mouse libraries were generated from laser microdissected tissue samples of dorsal VZ/SVZ (ventricular zone and subventricular zone) from the telencephalon of wild-type (Wt) and Nr2e1-null embryos at the critical development ages E13.5, E15.5, and E17.5. We then used a novel approach, implementing multiple computational methods followed by biological validation to further our understanding of Nr2e1 in neocortex development. In this work, we have generated a list of 1279 genes that are differentially expressed in response to altered Nr2e1 expression during in vivo neocortex development. We have refined this list to 64 candidate direct-targets of NR2E1. Our data suggested distinct roles for Nr2e1 during different neocortex developmental stages. Most importantly, our results suggest a possible novel pathway by which Nr2e1 regulates neurogenesis, which includes Lhx2 as one of the candidate direct-target genes, and SOX9 as a co-interactor. In conclusion, we have provided new candidate interacting partners and numerous well-developed testable hypotheses for understanding the pathways by which Nr2e1 functions to regulate neocortex development.

MicroRNA Cluster miR-17-92 Regulates Neural Stem Cell Expansion and Transition to Intermediate Progenitors in the Developing Mouse Neocortex

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Shan Bian

2013-05-01

Full Text Available During development of the embryonic neocortex, tightly regulated expansion of neural stem cells (NSCs and their transition to intermediate progenitors (IPs are critical for normal cortical formation and function. Molecular mechanisms that regulate NSC expansion and transition remain unclear. Here, we demonstrate that the microRNA (miRNA miR-17-92 cluster is required for maintaining proper populations of cortical radial glial cells (RGCs and IPs through repression of Pten and Tbr2 protein. Knockout of miR-17-92 and its paralogs specifically in the developing neocortex restricts NSC proliferation, suppresses RGC expansion, and promotes transition of RGCs to IPs. Moreover, Pten and Tbr2 protectors specifically block silencing activities of endogenous miR-17-92 and control proper numbers of RGCs and IPs in vivo. Our results demonstrate a critical role for miRNAs in promoting NSC proliferation and modulating the cell-fate decision of generating distinct neural progenitors in the developing neocortex.

Is forebrain neurogenesis a potential repair mechanism after stroke?

OpenAIRE

Inta, Dragos; Gass, Peter

2015-01-01

The use of adult subventricular zone (SVZ) neurogenesis as brain repair strategy after stroke represents a hot topic in neurologic research. Recent radiocarbon-14 dating has revealed a lack of poststroke neurogenesis in the adult human neocortex; however, adult neurogenesis has been shown to occur, even under physiologic conditions, in the human striatum. Here, these results are contrasted with experimental poststroke neurogenesis in the murine brain. Both in humans and in rodents, the SVZ ge...

GABAERGIC ALTERATIONS IN NEOCORTEX OF PATIENTS WITH PHARMACORESISTANT TEMPORAL LOBE EPILEPSY CAN EXPLAIN THE COMORBIDITY OF ANXIETY AND DEPRESSION: THE POTENTIAL IMPACT OF CLINICAL FACTORS

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Luisa Lilia Rocha

2015-01-01

Full Text Available Temporal lobe epilepsy (TLE is a chronic neurodegenerative disease with a high prevalence of psychiatric disorders. Temporal neocortex contributes to either seizure propagation or generation in TLE, a situation that has been associated with alterations of the γ-aminobutyric acid (GABA system. On the other hand, an impaired neurotransmission mediated by GABA in temporal neocortex has also been involved with the pathophysiology of psychiatric disorders. In spite of these situations, the role of the necortical GABA system in the comorbidity of TLE and mood disorders has not been investigated. The present study was designed to identify alterations in the GABA system such as: binding to GABAA and GABAB receptors and benzodiazepine site, the tissue content of GABA and the expression of the mRNA encoding the α1-6, β1-3 and γ GABAA subunits, in the temporal neocortex of surgically treated patients with TLE with and without anxiety and/or depression. Neocortex of patients with TLE and comorbid anxiety and/or depression showed increased expression of the mRNA encoding the γ2-subunit, reduced GABAB-induced G protein activation in spite of elevated GABAB binding, and lower tissue content of GABA when compared to autopsy controls. Some of these changes significantly correlated with seizure frequency and duration of epilepsy. The results obtained suggest a dysfunction of the GABAergic neurotransmission in temporal neocortex of patients with TLE and comorbid anxiety and/or depression that could be also influenced by clinical factors such as seizure frequency and duration of illness.

Recent Advances on the Role of Neurogenesis in the Adult Brain: Therapeutic Potential in Parkinson's and Alzheimer's Diseases.

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Radad, Khaled; Moldzio, Rudolf; Al-Shraim, Mubarak; Kranner, Barbara; Krewenka, Christopher; Rausch, Wolf-Dieter

2017-01-01

Generation of nascent functional neurons from neural stem cells in the adult brain has recently become largely accepted by the neuroscience community. In adult mammals including humans, the process of neurogenesis has been well documented in two brain regions; the subventricular zone of the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus. Some evidence has indicated neurogenesis in other regions of the adult mammalian brain such as the neocortex, cerebellum, striatum, amygdala and hypothalamus. These discoveries question a long standing dogma on nervous system regeneration and provide medical science with potential new strategies to harness the process of neurogenesis for treating neurological disabilities and neurodegenerative diseases. In this current review, we address the most recent advances on the role of neurogenesis in the adult brain and therapeutic potential in the two most common neurodegenerative disorders, Parkinson's and Alzheimer's diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Taurine activates GABAergic networks in the neocortex of immature mice

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Bogdan Aurel Sava

2014-02-01

Full Text Available Although it has been suggested that taurine is the main endogenous neurotransmitter acting on glycine receptors, the implications of glycine receptor-mediated taurine actions on immature neocortical networks have not been addressed yet. To investigate the influence of taurine on the excitability of neuronal networks in the immature neocortex, we performed whole-cell patch-clamp recordings from visually identified pyramidal neurons and interneurons in coronal slices from C57Bl/6 and GAD67-GFP transgenic mice (postnatal days 2-4. In 46 % of the pyramidal neurons bath-application of taurine at concentrations ≥ 300 mM significantly enhanced the frequency of postsynaptic currents (PSCs by 744.3 ± 93.8 % (n = 120 cells. This taurine-induced increase of PSC frequency was abolished by 0.2 mM tetrodotoxine, 1 mM strychnine or 3 mM gabazine, but was unaffected by the glutamatergic antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX and (± R(--3-(2-carboxypiperazine-4-yl-propyl-1-phosphonic acid (CPP, suggesting that taurine specifically activates GABAergic network activity projecting to pyramidal neurons. Cell-attached recordings revealed that taurine enhanced the frequency of action potentials in pyramidal neurons, indicating an excitatory action of the GABAergic PSCs. In order to identify the presynaptic targets of taurine we demonstrate that bath application of taurine induced in GAD67-GFP labeled interneurons an inward current that is mainly mediated by glycine receptors and can generate action potentials in these cells. We conclude from these results that taurine can enhance network excitability in the immature neocortex by selectively activating GABAergic interneurons via interactions with glycine receptors.

A single splice site mutation in human-specific ARHGAP11B causes basal progenitor amplification

Science.gov (United States)

Florio, Marta; Namba, Takashi; Pääbo, Svante; Hiller, Michael; Huttner, Wieland B.

2016-01-01

The gene ARHGAP11B promotes basal progenitor amplification and is implicated in neocortex expansion. It arose on the human evolutionary lineage by partial duplication of ARHGAP11A, which encodes a Rho guanosine triphosphatase–activating protein (RhoGAP). However, a lack of 55 nucleotides in ARHGAP11B mRNA leads to loss of RhoGAP activity by GAP domain truncation and addition of a human-specific carboxy-terminal amino acid sequence. We show that these 55 nucleotides are deleted by mRNA splicing due to a single C→G substitution that creates a novel splice donor site. We reconstructed an ancestral ARHGAP11B complementary DNA without this substitution. Ancestral ARHGAP11B exhibits RhoGAP activity but has no ability to increase basal progenitors during neocortex development. Hence, a single nucleotide substitution underlies the specific properties of ARHGAP11B that likely contributed to the evolutionary expansion of the human neocortex. PMID:27957544

Microglial and macrophage reactions mark progressive changes and define the penumbra in the rat neocortex and striatum after transient middle cerebral artery occlusion

DEFF Research Database (Denmark)

Lehrmann, E; Christensen, Thomas; Zimmer, J

1997-01-01

Transient middle cerebral artery occlusion in rats leads to infarction of the lateral part of the striatum and adjacent neocortex, with selective neuronal necrosis in the bordering penumbral zones. Administration of glutamate, cytokine, and leukocyte antagonists have rescued mainly neocortical....../macrophages in the adjacent penumbra. Within the neocortex, a later onset of degeneration along the insular-parietal axis was marked by neuronal expression of heat shock protein and a progressive microglial activation with induction of the full repertoire of microglial activation markers, including a widespread microglial...

Histological evidence for drug diffusion across the cerebral meninges into the underlying neocortex in rats.

Science.gov (United States)

Ludvig, Nandor; Sheffield, Lynette G; Tang, Hai M; Baptiste, Shirn L; Devinsky, Orrin; Kuzniecky, Ruben I

2008-01-10

Transmeningeal pharmacotherapy has been proposed to treat neurological disorders with localized pathology, such as intractable focal epilepsy. As a step toward understanding the diffusion and intracortical spread of transmeningeally delivered drugs, the present study used histological methods to determine the extent to which a marker compound, N-methyl-D-aspartate (NMDA), can diffuse into the neocortex through the meninges. Rats were implanted with bilateral parietal cortical epidural cups filled with 50 mM NMDA on the right side and artificial cerebrospinal fluid (ACSF) in the contralateral side. After 24 h, the histological effects of these treatments were evaluated using cresyl violet (Nissl) staining. The epidural NMDA exposure caused neuronal loss that in most animals extended from the pial surface through layer V. The area indicated by this neuronal loss was localized to the neocortical region underlying the epidural cup. These results suggest that NMDA-like, water soluble, small molecules can diffuse through the subdural/subarachnoid space into the underlying neocortex and spread in a limited fashion, close to the meningeal penetration site.

Structural bases of intracortical processes underlying the synchronization of epileptic potentials in the sensorimotor areas of the neocortex in rats.

Science.gov (United States)

Pasikova, N V; Marchenko, V G; Kositsyn, N S

2001-01-01

Studies in long-term isolated areas of the rat neocortex were performed to investigate the dynamics of the numbers and areas of nerve cell bodies in layer V and to compare these data with the degree of synchronization of epileptic discharges evoked by application of penicillin. Decreases in the number of pyramidal neurons with body areas of 200-350 microm2 in isolated strips after maintenance for 30 and 90 days led to decreases in the degree of synchronization of epileptiform potentials. Large pyramidal neurons are known to have long horizontal axon collaterals, spreading into layers V and VI of the neocortex. It is suggested that the neural networks formed by large pyramidal neurons by means of their long horizontal collaterals mediate the process of intracortical synchronization.

Cell number, tissue thickness and protein content as measures for development and variability in cultured neocortex explants

NARCIS (Netherlands)

de Jong, B. M.; Ruijter, J. M.

1989-01-01

The development of neuronal number, explant thickness and amount of protein was studied in several series of rat neocortex explants, cultured up to 21 days in vitro (DIV). In contrast to the dimensions of the explant, which rapidly stabilized, the amount of protein showed a prolonged increase with

Columnar interactions determine horizontal propagation of recurrent network activity in neocortex

Science.gov (United States)

Wester, Jason C.; Contreras, Diego

2012-01-01

The cortex is organized in vertical and horizontal circuits that determine the spatiotemporal properties of distributed cortical activity. Despite detailed knowledge of synaptic interactions among individual cells in the neocortex, little is known about the rules governing interactions among local populations. Here we used self-sustained recurrent activity generated in cortex, also known as up-states, in rat thalamocortical slices in vitro to understand interactions among laminar and horizontal circuits. By means of intracellular recordings and fast optical imaging with voltage sensitive dyes, we show that single thalamic inputs activate the cortical column in a preferential L4→L2/3→L5 sequence, followed by horizontal propagation with a leading front in supra and infragranular layers. To understand the laminar and columnar interactions, we used focal injections of TTX to block activity in small local populations, while preserving functional connectivity in the rest of the network. We show that L2/3 alone, without underlying L5, does not generate self-sustained activity and is inefficient propagating activity horizontally. In contrast, L5 sustains activity in the absence of L2/3 and is necessary and sufficient to propagate activity horizontally. However, loss of L2/3 delays horizontal propagation via L5. Finally, L5 amplifies activity in L2/3. Our results show for the first time that columnar interactions between supra and infragranular layers are required for the normal propagation of activity in the neocortex. Our data suggest that supra and infragranular circuits with their specific and complex set of inputs and outputs, work in tandem to determine the patterns of cortical activation observed in vivo. PMID:22514308

Quantitative analysis of neuronal mosaic formation in the mouse neocortex and hippocampus

International Nuclear Information System (INIS)

Reznikov, K.Yu.; Nazarevskaya, G.D.; Deryabin, V.E.

1987-01-01

The authors obtain mathematical confirmation of the nonrandomness of mosaic formation of neuronal groups in the cerebral cortex, characterize this process quantitatively, and compare its scale with the formation of the modular organization of the cortex. Mice were used in the experiments and were injected with 3 H-thymidine while pregnant. Mapping in the neocortex was carried out on frontal semithin brain sections from mice receiving 3 H-thymidine from E15 through E17, whereas mapping in the hippocampus was carried out on paraffin and semithin frontal brain sections from animals receiving the isotope from E13 through E17

Spatiotemporal distribution of PAX6 and MEIS2 expression and total cell numbers in the ganglionic eminence in the early developing human forebrain

DEFF Research Database (Denmark)

Larsen, Karen B; Lutterodt, Melissa C; Laursen, Henning

2010-01-01

The development of the human neocortex is a complex and highly regulated process involving a time-related expression of many transcription factors including the homeobox genes Pax6 and Meis2. During early development, Pax6 is expressed in nuclei of radial glia cells in the neocortical proliferative...... in the same time window. We demonstrate by in situ hybridization and immunohistochemistry that the two homeobox genes are expressed during early fetal brain development in humans. PAX6 mRNA and protein were located in the proliferative zones of the neocortex and in single cells in the cortical preplate at 7...... in the proliferative zones of the human fetal neocortex and a higher expression of MEIS2 than PAX6 was observed in these areas at 9 fetal weeks. Further, MEIS2 was expressed at a very high level in the developing ganglionic eminence and at a more moderate level in the cortical plate....

BDNF Val66met and 5-HTTLPR polymorphisms predict a human in vivo marker for brain serotonin levels

DEFF Research Database (Denmark)

Fisher, Patrick M; Holst, Klaus K; Adamsen, Dea

2015-01-01

) polymorphism. We applied a linear latent variable model (LVM) using regional 5-HT4 binding values (neocortex, amygdala, caudate, hippocampus, and putamen) from 68 healthy humans, allowing us to explicitly model brain-wide and region-specific genotype effects on 5-HT4 binding. Our data supported an LVM wherein...... specifically affects 5-HT4 binding in the neocortex. These findings implicate serotonin signaling as an important molecular mediator underlying the effects of BDNF val66met and 5-HTTLPR on behavior and related risk for neuropsychiatric illness in humans. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc....

Disruption of the blood-brain interface in neonatal rat neocortex induces a transient expression of metallothionein in reactive astrocytes

DEFF Research Database (Denmark)

Penkowa, M; Moos, T

1995-01-01

rats were subjected to a localized freeze lesion of the neocortex of the right temporal cortex. This lesion results in a disrupted blood-brain interface, leading to extravasation of plasma proteins. From 16 h, reactive astrocytosis, defined as an increase in the number and size of cells expressing GFAP...

Analysis of stability and bifurcations of fixed points and periodic solutions of a lumped model of neocortex with two delays

NARCIS (Netherlands)

Visser, Sid; Meijer, Hil G.E.; van Putten, Michel J.A.M.; van Gils, Stephan A.

2012-01-01

A lumped model of neural activity in neocortex is studied to identify regions of multi-stability of both steady states and periodic solutions. Presence of both steady states and periodic solutions is considered to correspond with epileptogenesis. The model, which consists of two delay differential

Have you got any cholesterol? Adults' views of human nutrition

Science.gov (United States)

Schibeci, Renato; Wong, Khoon Yoong

1994-12-01

The general aim of our human nutrition project is to develop a health education model grounded in ‘everyday’ or ‘situated’ cognition (Hennessey, 1993). In 1993, we began pilot work to document adult understanding of human nutrition. We used a HyperCard stack as the basis for a series of interviews with 50 adults (25 university students, and 25 adults from offcampus). The interviews were transcribed and analysed using the NUDIST computer program. A summary of the views of these 50 adults on selected aspects of human nutrition is presented in this paper.

Neocortical glial cell numbers in human brains.

Science.gov (United States)

Pelvig, D P; Pakkenberg, H; Stark, A K; Pakkenberg, B

2008-11-01

Stereological cell counting was applied to post-mortem neocortices of human brains from 31 normal individuals, age 18-93 years, 18 females (average age 65 years, range 18-93) and 13 males (average age 57 years, range 19-87). The cells were differentiated in astrocytes, oligodendrocytes, microglia and neurons and counting were done in each of the four lobes. The study showed that the different subpopulations of glial cells behave differently as a function of age; the number of oligodendrocytes showed a significant 27% decrease over adult life and a strong correlation to the total number of neurons while the total astrocyte number is constant through life; finally males have a 28% higher number of neocortical glial cells and a 19% higher neocortical neuron number than females. The overall total number of neocortical neurons and glial cells was 49.3 billion in females and 65.2 billion in males, a difference of 24% with a high biological variance. These numbers can serve as reference values in quantitative studies of the human neocortex.

Transcriptional profiling of adult neural stem-like cells from the human brain.

Directory of Open Access Journals (Sweden)

Cecilie Jonsgar Sandberg

Full Text Available There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60. Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate. We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6, foetal human neural stem cells (n = 1 and human brain tissues (n = 12. The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular

Unravelling Boléro: progressive aphasia, transmodal creativity and the right posterior neocortex.

Science.gov (United States)

Seeley, William W; Matthews, Brandy R; Crawford, Richard K; Gorno-Tempini, Maria Luisa; Foti, Dean; Mackenzie, Ian R; Miller, Bruce L

2008-01-01

Most neurological lesion studies emphasize performance deficits that result from focal brain injury. Here, we describe striking gains of function in a patient with primary progressive aphasia, a degenerative disease of the human language network. During the decade before her language deficits arose, Anne Adams (AA), a lifelong scientist, developed an intense drive to produce visual art. Paintings from AA's artistic peak revealed her capacity to create expressive transmodal art, such as renderings of music in paint, which may have reflected an increased subjective relatedness among internal perceptual and conceptual images. AA became fascinated with Maurice Ravel, the French composer who also suffered from a progressive aphasia, and painted his best-known work, 'Boléro', by translating its musical elements into visual form. Later paintings, achieved when AA was nearly mute, moved towards increasing photographic realism, perhaps because visual representations came to dominate AA's mental landscape during this phase of her illness. Neuroimaging analyses revealed that, despite severe degeneration of left inferior frontal-insular, temporal and striatal regions, AA showed increased grey matter volume and hyperperfusion in right posterior neocortical areas implicated in heteromodal and polysensory integration. The findings suggest that structural and functional enhancements in non-dominant posterior neocortex may give rise to specific forms of visual creativity that can be liberated by dominant inferior frontal cortex injury.

An RNA gene expressed during cortical development evolved rapidly in humans

DEFF Research Database (Denmark)

Pollard, Katherine S; Salama, Sofie R; Lambert, Nelle

2006-01-01

in the developing human neocortex from 7 to 19 gestational weeks, a crucial period for cortical neuron specification and migration. HAR1F is co-expressed with reelin, a product of Cajal-Retzius neurons that is of fundamental importance in specifying the six-layer structure of the human cortex. HAR1 and the other...

Qualitative analysis neurons in the adult human dentate nucleus

Directory of Open Access Journals (Sweden)

Marić Dušica

2012-01-01

Full Text Available Although many relevant findings regarding to the morphology and cytoarchitectural development of the dentate nucleus have been presented so far, very little qualitative information has been collected on neuronal morphology in the adult human dentate nucleus. The neurons were labelled by Golgi staining from thirty human cerebella, obtained from medico-legal forensic autopsies of adult human bodies and free of significant brain pathology. The human dentate neurons were qualitatively analyzed and these cells were classified into two main classes: the small and the large multipolar neurons. Considering the shape of the cell body, number of the primary dendrites, shape of the dendritic tree and their position within the dentate nucleus, three subclasses of the large multipolar neurons have been recognized. The classification of neurons from the human dentate nucleus has been qualitatively confirmed in fetuses and premature infants. This study represents the first qualitative analysis and classification of the large multipolar neurons in the dentate nucleus of the adult human.

Activin receptor subunits in normal and dysfunctional adult human testis

DEFF Research Database (Denmark)

Dias, V; Meachem, S; Rajpert-De Meyts, E

2008-01-01

The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown.......The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown....

Adult Education & Human Resource Development: Overlapping and Disparate Fields

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Watkins, Karen E.; Marsick, Victoria J.

2014-01-01

Adult education and human resource development as fields of practice and study share some roots in common but have grown in different directions in their histories. Adult education's roots focused initially on citizenship for a democratic society, whereas human resource development's roots are in performance at work. While they have…

Germline stem cells and neo-oogenesis in the adult human ovary.

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Liu, Yifei; Wu, Chao; Lyu, Qifeng; Yang, Dongzi; Albertini, David F; Keefe, David L; Liu, Lin

2007-06-01

It remains unclear whether neo-oogenesis occurs in postnatal ovaries of mammals, based on studies in mice. We thought to test whether adult human ovaries contain germline stem cells (GSCs) and undergo neo-oogenesis. Rather than using genetic manipulation which is unethical in humans, we took the approach of analyzing the expression of meiotic marker genes and genes for germ cell proliferation, which are required for neo-oogenesis, in adult human ovaries covering an age range from 28 to 53 years old, compared to testis and fetal ovaries served as positive controls. We show that active meiosis, neo-oogenesis and GSCs are unlikely to exist in normal, adult, human ovaries. No early meiotic-specific or oogenesis-associated mRNAs for SPO11, PRDM9, SCP1, TERT and NOBOX were detectable in adult human ovaries using RT-PCR, compared to fetal ovary and adult testis controls. These findings are further corroborated by the absence of early meiocytes and proliferating germ cells in adult human ovarian cortex probed with markers for meiosis (SCP3), oogonium (OCT3/4, c-KIT), and cell cycle progression (Ki-67, PCNA), in contrast to fetal ovary controls. If postnatal oogenesis is confirmed in mice, then this species would represent an exception to the rule that neo-oogenesis does not occur in adults.

Monoaminergic Control of Cellular Glucose Utilization by Glycogenolysis in Neocortex and Hippocampus.

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DiNuzzo, Mauro; Giove, Federico; Maraviglia, Bruno; Mangia, Silvia

2015-12-01

Brainstem nuclei are the principal sites of monoamine (MA) innervation to major forebrain structures. In the cortical grey matter, increased secretion of MA neuromodulators occurs in response to a wealth of environmental and homeostatic challenges, whose onset is associated with rapid, preparatory changes in neural activity as well as with increases in energy metabolism. Blood-borne glucose is the main substrate for energy production in the brain. Once entered the tissue, interstitial glucose is equally accessible to neurons and astrocytes, the two cell types accounting for most of cellular volume and energy metabolism in neocortex and hippocampus. Astrocytes also store substantial amounts of glycogen, but non-stimulated glycogen turnover is very small. The rate of cellular glucose utilization in the brain is largely determined by hexokinase, which under basal conditions is more than 90 % inhibited by its product glucose-6-phosphate (Glc-6-P). During rapid increases in energy demand, glycogen is a primary candidate in modulating the intracellular level of Glc-6-P, which can occur only in astrocytes. Glycogenolysis can produce Glc-6-P at a rate higher than uptake and phosphorylation of glucose. MA neurotransmitter are released extrasinaptically by brainstem neurons projecting to neocortex and hippocampus, thus activating MA receptors located on both neuronal and astrocytic plasma membrane. Importantly, MAs are glycogenolytic agents and thus they are exquisitely suitable for regulation of astrocytic Glc-6-P concentration, upstream substrate flow through hexokinase and hence cellular glucose uptake. Conforming to such mechanism, Gerald A. Dienel and Nancy F. Cruz recently suggested that activation of noradrenergic locus coeruleus might reversibly block astrocytic glucose uptake by stimulating glycogenolysis in these cells, thereby anticipating the rise in glucose need by active neurons. In this paper, we further develop the idea that the whole monoaminergic system

BIG1 is required for the survival of deep layer neurons, neuronal polarity, and the formation of axonal tracts between the thalamus and neocortex in developing brain.

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Jia-Jie Teoh

Full Text Available BIG1, an activator protein of the small GTPase, Arf, and encoded by the Arfgef1 gene, is one of candidate genes for epileptic encephalopathy. To know the involvement of BIG1 in epileptic encephalopathy, we analyzed BIG1-deficient mice and found that BIG1 regulates neurite outgrowth and brain development in vitro and in vivo. The loss of BIG1 decreased the size of the neocortex and hippocampus. In BIG1-deficient mice, the neuronal progenitor cells (NPCs and the interneurons were unaffected. However, Tbr1+ and Ctip2+ deep layer (DL neurons showed spatial-temporal dependent apoptosis. This apoptosis gradually progressed from the piriform cortex (PIR, peaked in the neocortex, and then progressed into the hippocampus from embryonic day 13.5 (E13.5 to E17.5. The upper layer (UL and DL order in the neocortex was maintained in BIG1-deficient mice, but the excitatory neurons tended to accumulate before their destination layers. Further pulse-chase migration assay showed that the migration defect was non-cell autonomous and secondary to the progression of apoptosis into the BIG1-deficient neocortex after E15.5. In BIG1-deficient mice, we observed an ectopic projection of corticothalamic axons from the primary somatosensory cortex (S1 into the dorsal lateral geniculate nucleus (dLGN. The thalamocortical axons were unable to cross the diencephalon-telencephalon boundary (DTB. In vitro, BIG1-deficient neurons showed a delay in neuronal polarization. BIG1-deficient neurons were also hypersensitive to low dose glutamate (5 μM, and died via apoptosis. This study showed the role of BIG1 in the survival of DL neurons in developing embryonic brain and in the generation of neuronal polarity.

Comparative Analysis Between Flaviviruses Reveals Specific Neural Stem Cell Tropism for Zika Virus in the Mouse Developing Neocortex

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Jean-Baptiste Brault

2016-08-01

Full Text Available The recent Zika outbreak in South America and French Polynesia was associated with an epidemic of microcephaly, a disease characterized by a reduced size of the cerebral cortex. Other members of the Flavivirus genus, including West Nile virus (WNV, can cause encephalitis but were not demonstrated to cause microcephaly. It remains unclear whether Zika virus (ZIKV and other flaviviruses may infect different cell populations in the developing neocortex and lead to distinct developmental defects. Here, we describe an assay to infect mouse E15 embryonic brain slices with ZIKV, WNV and dengue virus serotype 4 (DENV-4. We show that this tissue is able to support viral replication of ZIKV and WNV, but not DENV-4. Cell fate analysis reveals a remarkable tropism of ZIKV infection for neural stem cells. Closely related WNV displays a very different tropism of infection, with a bias towards neurons. We further show that ZIKV infection, but not WNV infection, impairs cell cycle progression of neural stem cells. Both viruses inhibited apoptosis at early stages of infection. This work establishes a powerful comparative approach to identify ZIKV-specific alterations in the developing neocortex and reveals specific preferential infection of neural stem cells by ZIKV.

In-vivo magnetic resonance imaging (MRI) of laminae in the human cortex

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Trampel, Robert; Bazin, Pierre-Louis; Pine, Kerrin; Weiskopf, Nikolaus

2018-01-01

The human neocortex is organized radially into six layers which differ in their myelination and the density and arrangement of neuronal cells. This cortical cyto- and myeloarchitecture plays a central role in the anatomical and functional neuroanatomy but is primarily accessible through invasive

Cortical GABAergic excitation contributes to epileptic activities around human glioma

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Pallud, Johan; Varlet, Pascale; Cresto, Noemie; Baulac, Michel; Duyckaerts, Charles; Kourdougli, Nazim; Chazal, Geneviève; Devaux, Bertrand; Rivera, Claudio; Miles, Richard; Capelle, Laurent; Huberfeld, Gilles

2015-01-01

Rationale Diffuse brain gliomas induce seizures in a majority of patients. As in most epileptic disorders, excitatory glutamatergic mechanisms are involved in the generation of epileptic activities in the neocortex surrounding gliomas. However, chloride homeostasis is known to be perturbed in glial tumor cells. Thus the contribution of GABAergic mechanisms which depend on intracellular chloride and which are defective or pro-epileptic in other structural epilepsies merits closer study. Objective We studied in neocortical slices from the peritumoral security margin resected around human brain gliomas, the occurrence, networks, cells and signaling basis of epileptic activities. Results Postoperative glioma tissue from 69% of patients spontaneously generated interictal-like discharges. These events were synchronized, with a high frequency oscillation signature, in superficial layers of neocortex around glioma areas with tumor infiltration. Interictal-like events depended on both glutamatergic transmission and on depolarizing GABAergic signaling. About 65% of pyramidal cells were depolarized by GABA released by interneurons. This effect was related to perturbations in Chloride homeostasis, due to changes in expression of chloride co-transporters: KCC2 was reduced and expression of NKCC1 increased. Ictal-like activities were initiated by convulsant stimuli exclusively in these epileptogenic areas. Conclusions Epileptic activities are sustained by excitatory effects of GABA in the peritumoral human neocortex, as in temporal lobe epilepsies. Glutamate and GABA signaling are involved in oncogenesis and chloride homeostasis is perturbed. These same factors, induce an imbalance between synaptic excitatory and inhibition underly epileptic discharges in tumor patients. PMID:25009229

Adult Functional Literacy Curriculum: Effective Strategy for Human ...

African Journals Online (AJOL)

Adult functional literacy curriculum no doubt, is a panacea to human resource development in Nigeria. Government and non-government organizations have roles to play in providing functional education to adults who drop out of school or have no opportunity of attending the formal school system for all round development.

Defective neuronal migration and inhibition of bipolar to multipolar transition of migrating neural cells by Mesoderm-Specific Transcript, Mest, in the developing mouse neocortex.

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Ji, Liting; Bishayee, Kausik; Sadra, Ali; Choi, Seunghyuk; Choi, Wooyul; Moon, Sungho; Jho, Eek-Hoon; Huh, Sung-Oh

2017-07-04

Brain developmental disorders such as lissencephaly can result from faulty neuronal migration and differentiation during the formation of the mammalian neocortex. The cerebral cortex is a modular structure, where developmentally, newborn neurons are generated as a neuro-epithelial sheet and subsequently differentiate, migrate and organize into their final positions in the cerebral cortical plate via a process involving both tangential and radial migration. The specific role of Mest, an imprinted gene, in neuronal migration has not been previously studied. In this work, we reduced expression of Mest with in utero electroporation of neuronal progenitors in the developing embryonic mouse neocortex. Reduction of Mest levels by shRNA significantly reduced the number of neurons migrating to the cortical plate. Also, Mest-knockdown disrupted the transition of bipolar neurons into multipolar neurons migrating out of the sub-ventricular zone region. The migrating neurons also adopted a more tangential migration pattern upon knockdown of the Mest message, losing their potential to attach to radial glia cells, required for radial migration. The differentiation and migration properties of neurons via Wnt-Akt signaling were affected by Mest changes. In addition, miR-335, encoded in a Mest gene intron, was identified as being responsible for blocking the default tangential migration of the neurons. Our results suggest that Mest and its intron product, miR-335, play important roles in neuronal migration with Mest regulating the morphological transition of primary neurons required in the formation of the mammalian neocortex. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

In vitro proliferation of adult human beta-cells.

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Sabine Rutti

Full Text Available A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1 analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide.Human islets from 7 adult cadaveric organ donors were dispersed into single cells. Beta-cells were purified by FACS. Non-sorted cells and the beta-cell enriched ("beta-cells" population were plated on extracellular matrix from rat (804G and human bladder carcinoma cells (HTB9 or bovine corneal endothelial ECM (BCEC. Cells were maintained in culture+/-liraglutide for 4 days in the presence of BrdU.Rare human beta-cell proliferation could be observed either in the purified beta-cell population (0.051±0.020%; 22 beta-cells proliferating out of 84'283 beta-cells counted or in the non-sorted cell population (0.055±0.011%; 104 proliferating beta-cells out of 232'826 beta-cells counted, independently of the matrix or the culture conditions. Liraglutide increased human beta-cell proliferation on BCEC in the non-sorted cell population (0.082±0.034% proliferating beta-cells vs. 0.017±0.008% in control, p<0.05.These results indicate that adult human beta-cell proliferation can occur in vitro but remains an extremely rare event with these donors and particular culture conditions. Liraglutide increases beta-cell proliferation only in the non-sorted cell population and only on BCEC. However, it cannot be excluded that human beta-cells may proliferate to a greater extent in situ in response to natural stimuli.

Editorial: Technology for higher education, adult learning and human performance

OpenAIRE

Minhong Wang; Chi-Cheng Chang; Feng Wu

2013-01-01

This special issue is dedicated to technology-enabled approaches for improving higher education, adult learning, and human performance. Improvement of learning and human development for sustainable development has been recognized as a key strategy for individuals, institutions, and organizations to strengthen their competitive advantages. It becomes crucial to help adult learners and knowledge workers to improve their self-directed and life-long learning capabilities. Meanwhile, advances in t...

Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older Adults.

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Lissner, Michelle M; Thomas, Brandon J; Wee, Kathleen; Tong, Ann-Jay; Kollmann, Tobias R; Smale, Stephen T

2015-01-01

A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development.

[{sup 125}I]{beta}-CIT-FE and [{sup 125}I]{beta}-CIT-FP are superior to [{sup 125}I]{beta}-CIT for dopamine transporter visualization: Autoradiographic evaluation in the human brain

Energy Technology Data Exchange (ETDEWEB)

Guenther, Ilonka; Hall, Haakan; Halldin, Christer; Swahn, Carl-Gunnar; Farde, Lars; Sedvall, Goeran

1997-10-01

The binding of the three dopamine transporter radioligands ([{sup 125}I]{beta}-CIT, [{sup 125}I]{beta}-CIT-FE, and [{sup 125}I]{beta}-CIT-FP) was studied using whole-hemisphere autoradiography on postmortem human brains. The autoradiograms revealed an intense and homogeneous labeling of the nucleus caudatus and putamen but also to varying extent to serotonergic and noradrenergic transporters of neocortex and thalamus. The order of specificity estimated (striatum over neocortex ratios) was {beta}-CIT-FP > {beta}-CIT-FE >> {beta}-CIT, suggesting that {beta}-CIT-FE and {beta}-CIT-FP should be preferred for in vivo studies of the dopamine transporter in the human brain.

The weight of nations: an estimation of adult human biomass

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Walpole Sarah

2012-06-01

Full Text Available Abstract Background The energy requirement of species at each trophic level in an ecological pyramid is a function of the number of organisms and their average mass. Regarding human populations, although considerable attention is given to estimating the number of people, much less is given to estimating average mass, despite evidence that average body mass is increasing. We estimate global human biomass, its distribution by region and the proportion of biomass due to overweight and obesity. Methods For each country we used data on body mass index (BMI and height distribution to estimate average adult body mass. We calculated total biomass as the product of population size and average body mass. We estimated the percentage of the population that is overweight (BMI > 25 and obese (BMI > 30 and the biomass due to overweight and obesity. Results In 2005, global adult human biomass was approximately 287 million tonnes, of which 15 million tonnes were due to overweight (BMI > 25, a mass equivalent to that of 242 million people of average body mass (5% of global human biomass. Biomass due to obesity was 3.5 million tonnes, the mass equivalent of 56 million people of average body mass (1.2% of human biomass. North America has 6% of the world population but 34% of biomass due to obesity. Asia has 61% of the world population but 13% of biomass due to obesity. One tonne of human biomass corresponds to approximately 12 adults in North America and 17 adults in Asia. If all countries had the BMI distribution of the USA, the increase in human biomass of 58 million tonnes would be equivalent in mass to an extra 935 million people of average body mass, and have energy requirements equivalent to that of 473 million adults. Conclusions Increasing population fatness could have the same implications for world food energy demands as an extra half a billion people living on the earth.

Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

Science.gov (United States)

Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

2016-01-01

Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Immunohistochemical Markers for Quantitative Studies of Neurons and Glia in Human Neocortex

DEFF Research Database (Denmark)

Lyck, Lise; Dalmau, Ishar; Chemnitz, John

2007-01-01

Reproducible visualisation of neurons and glia in human brain is essential for quantitative studies of the cellular changes in neurological disease. However, immunohistochemistry in human brain specimens is often compromised due to prolonged fixation. To select cell-lineage specific antibodies fo...

Neurogenic radial glia in the outer subventricular zone of human neocortex.

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Hansen, David V; Lui, Jan H; Parker, Philip R L; Kriegstein, Arnold R

2010-03-25

Neurons in the developing rodent cortex are generated from radial glial cells that function as neural stem cells. These epithelial cells line the cerebral ventricles and generate intermediate progenitor cells that migrate into the subventricular zone (SVZ) and proliferate to increase neuronal number. The developing human SVZ has a massively expanded outer region (OSVZ) thought to contribute to cortical size and complexity. However, OSVZ progenitor cell types and their contribution to neurogenesis are not well understood. Here we show that large numbers of radial glia-like cells and intermediate progenitor cells populate the human OSVZ. We find that OSVZ radial glia-like cells have a long basal process but, surprisingly, are non-epithelial as they lack contact with the ventricular surface. Using real-time imaging and clonal analysis, we demonstrate that these cells can undergo proliferative divisions and self-renewing asymmetric divisions to generate neuronal progenitor cells that can proliferate further. We also show that inhibition of Notch signalling in OSVZ progenitor cells induces their neuronal differentiation. The establishment of non-ventricular radial glia-like cells may have been a critical evolutionary advance underlying increased cortical size and complexity in the human brain.

The Synaptic Proteome during Development and Plasticity of the Mouse Visual Cortex

NARCIS (Netherlands)

Dahlhaus, M.; Li, K.W.; van der Schors, R.C.; Saiepour, M.H.; van Nierop, P.; Heimel, J.A.; Hermans, J.M.; Loos, M.; Smit, A.B.; Levelt, C.N.

2011-01-01

During brain development, the neocortex shows periods of enhanced plasticity, which enables the acquisition of knowledge and skills that we use and build on in adult life. Key to persistent modifications of neuronal connectivity and plasticity of the neocortex are molecular changes occurring at the

Diluted connectivity in pattern association networks facilitates the recall of information from the hippocampus to the neocortex.

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Rolls, Edmund T

2015-01-01

The recall of information stored in the hippocampus involves a series of corticocortical backprojections via the entorhinal cortex, parahippocampal gyrus, and one or more neocortical stages. Each stage is considered to be a pattern association network, with the retrieval cue at each stage the firing of neurons in the previous stage. The leading factor that determines the capacity of this multistage pattern association backprojection pathway is the number of connections onto any one neuron, which provides a quantitative basis for why there are as many backprojections between adjacent stages in the hierarchy as forward projections. The issue arises of why this multistage backprojection system uses diluted connectivity. One reason is that a multistage backprojection system with expansion of neuron numbers at each stage enables the hippocampus to address during recall the very large numbers of neocortical neurons, which would otherwise require hippocampal neurons to make very large numbers of synapses if they were directly onto neocortical neurons. The second reason is that as shown here, diluted connectivity in the backprojection pathways reduces the probability of more than one connection onto a receiving neuron in the backprojecting pathways, which otherwise reduces the capacity of the system, that is the number of memories that can be recalled from the hippocampus to the neocortex. For similar reasons, diluted connectivity is advantageous in pattern association networks in other brain systems such as the orbitofrontal cortex and amygdala; for related reasons, in autoassociation networks in, for example, the hippocampal CA3 and the neocortex; and for the different reason that diluted connectivity facilitates the operation of competitive networks in forward-connected cortical systems. © 2015 Elsevier B.V. All rights reserved.

Can sleep deprivation studies explain why human adults sleep?

Science.gov (United States)

Brown, Lee K

2012-11-01

This review will concentrate on the consequences of sleep deprivation in adult humans. These findings form a paradigm that serves to demonstrate many of the critical functions of the sleep states. The drive to obtain food, water, and sleep constitutes important vegetative appetites throughout the animal kingdom. Unlike nutrition and hydration, the reasons for sleep have largely remained speculative. When adult humans are nonspecifically sleep-deprived, systemic effects may include defects in cognition, vigilance, emotional stability, risk-taking, and, possibly, moral reasoning. Appetite (for foodstuffs) increases and glucose intolerance may ensue. Procedural, declarative, and emotional memory are affected. Widespread alterations of immune function and inflammatory regulators can be observed, and functional MRI reveals profound changes in regional cerebral activity related to attention and memory. Selective deprivation of rapid eye movement (REM) sleep, on the contrary, appears to be more activating and to have lesser effects on immunity and inflammation. The findings support a critical need for sleep due to the widespread effects on the adult human that result from nonselective sleep deprivation. The effects of selective REM deprivation appear to be different and possibly less profound, and the functions of this sleep state remain enigmatic.

Contact and perspective taking improve humanness standards and perceptions of humanness of older adults and people with dementia: a cross-sectional survey study.

Science.gov (United States)

Miron, Anca M; McFadden, Susan H; Hermus, Nathan J; Buelow, Jennifer; Nazario, Amanda S; Seelman, Katarena

2017-10-01

No empirical work has systematically explored perceptions of humanness of people with dementia and of older adults and the variables that could improve these perceptions. We thus investigated the role of contact and perspective taking in improving perceptions of humanness of these social groups. To do so, we developed a new concept, humanness standards, defined as the amount of evidence of ability impairment needed to conclude that elderly people and those with dementia have lost personhood. We used a cross-sectional survey design (n = 619) to assess participants' humanness standards and perceptions of uniquely human characteristics and human nature characteristics of two social groups (people with dementia and older adults). Half the participants (n = 311) completed a survey about people with dementia and half (n = 308) assessed older adults. People with dementia were perceived as possessing humanness characteristics to a lesser extent than were older adults. For both groups, contact predicted enhanced perceptions of humanness characteristics. Participants' degree of contact with individuals with dementia also predicted humanness standards, but only under low perspective-taking conditions. As predicted, for older adults, participants set the highest humanness impairment thresholds in the high contact/high perspective-taking condition. We conclude that while social programs that bring persons with dementia and other individuals in contact could change humanness standards and perceptions of humanness characteristics of people with dementia, in the case of elderly adults, the contact must be supplemented by variables that facilitate taking the perspective of the person.

Oogenesis in cultures derived from adult human ovaries

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Caudle Michael R

2005-05-01

Full Text Available Abstract Ten years ago, we reported that in adult human females the ovarian surface epithelium (OSE is a source of germ cells. Recently, we also demonstrated that new primary follicles are formed by assembly of oocytes with nests of primitive granulosa cells in the ovarian cortex. The components of the new primary follicles, primitive granulosa and germ cells, differentiated sequentially from the OSE, which arises from cytokeratin positive mesenchymal progenitor cells residing in the ovarian tunica albuginea. In the present study, we investigated the possibility that the oocytes and granulosa cells may differentiate in cultures derived from adult human ovaries. Cells were scrapped from the surface of ovaries and cultured for 5 to 6 days, in the presence or absence of estrogenic stimuli [phenol red (PhR]. The OSE cells cultured in the medium without PhR differentiated into small (15 micron cells of granulosa phenotype, and epithelial, neural, and mesenchymal type cells. In contrast, OSE cells cultured in the presence of PhR differentiated directly into large (180 micron cells of the oocyte phenotype. Such cells exhibited germinal vesicle breakdown, expulsion of the polar body, and surface expression of zona pellucida proteins, i.e. characteristics of secondary oocytes. These in vitro studies confirm our in vivo observations that in adult human ovaries, the OSE is a bipotent source of oocytes and granulosa cells. Development of numerous mature oocytes from adult ovarian stem cells in vitro offers new strategies for the egg preservation, IVF utilization, and treatment of female infertility. In addition, other clinical applications aiming to utilize stem cells, and basic stem cell research as well, may employ totipotent embryonic stem cells developing from fertilized oocytes.

Distinct functional programming of human fetal and adult monocytes.

Science.gov (United States)

Krow-Lucal, Elisabeth R; Kim, Charles C; Burt, Trevor D; McCune, Joseph M

2014-03-20

Preterm birth affects 1 out of 9 infants in the United States and is the leading cause of long-term neurologic handicap and infant mortality, accounting for 35% of all infant deaths in 2008. Although cytokines including interferon-γ (IFN-γ), interleukin-10 (IL-10), IL-6, and IL-1 are produced in response to in utero infection and are strongly associated with preterm labor, little is known about how human fetal immune cells respond to these cytokines. We demonstrate that fetal and adult CD14(+)CD16(-) classical monocytes are distinct in terms of basal transcriptional profiles and in phosphorylation of signal transducers and activators of transcription (STATs) in response to cytokines. Fetal monocytes phosphorylate canonical and noncanonical STATs and respond more strongly to IFN-γ, IL-6, and IL-4 than adult monocytes. We demonstrate a higher ratio of SOCS3 to IL-6 receptor in adult monocytes than in fetal monocytes, potentially explaining differences in STAT phosphorylation. Additionally, IFN-γ signaling results in upregulation of antigen presentation and costimulatory machinery in adult, but not fetal, monocytes. These findings represent the first evidence that primary human fetal and adult monocytes are functionally distinct, potentially explaining how these cells respond differentially to cytokines implicated in development, in utero infections, and the pathogenesis of preterm labor.

Understanding Older Adult's Perceptions of Factors that Support Trust in Human and Robot Care Providers.

Science.gov (United States)

Stuck, Rachel E; Rogers, Wendy A

2017-06-01

As the population of older adults increase so will the need for care providers, both human and robot. Trust is a key aspect to establish and maintain a successful older adult-care provider relationship. However, due to trust volatility it is essential to understand it within specific contexts. This proposed mixed methods study will explore what dimensions of trust emerge as important within the human-human and human-robot dyads in older adults and care providers. First, this study will help identify key qualities that support trust in a care provider relationship. By understanding what older adults perceive as needing to trust humans and robots for various care tasks, we can begin to provide recommendations based on user expectations for design to support trust.

Does Acute Normobaric Hypoxia Induce Anapyrexia in Adult Humans?

Science.gov (United States)

Seo, Yongsuk; Gerhart, Hayden D; Vaughan, Jeremiah; Kim, Jung-Hyun; Glickman, Ellen L

2017-06-01

Seo, Yongsuk, Hayden D. Gerhart, Jeremiah Vaughan, Jung-Hyun Kim, and Ellen L. Glickman. Does acute normobaric hypoxia induce anapyrexia in adult humans? High Alt Med Biol. 18:185-190, 2017.-Exposure to hypoxia is known to induce a reduction in core body temperature as a protective mechanism, which has been shown in both animals and humans. The purpose of this study was to test if acute exposure to normobaric hypoxia (NH) induces anapyrexia in adult humans in association with decreased peripheral oxygen saturation (SpO 2 ). Ten healthy male subjects were seated in atmospheres of normobaric normoxia 21% (NN21), NH 17% (NH17), and 13% (NH13) O 2 for 60 minutes in a counterbalanced manner. Rectal temperature (Tre) was continuously monitored together with the quantification of metabolic heat production (MHP) and body heat storage (S). Baseline physiological measurements showed no differences between the three conditions. SpO 2 was significantly decreased in NH17 and NH13 compared with NN21 (p ≤ 0.001). Tre decreased following 60 minutes of resting in all conditions, but, independent of the conditions, showed no association between Tre and levels of hypoxic SpO 2 . There was also no significant difference in either MHP or S between conditions. The present results showed no evidence of hypoxia-induced anapyrexia in adult humans during 1 hour of resting after exposure to NH either at 13% or 17% O 2 .

Phosphoinositide-3-kinases p110alpha and p110beta mediate S phase entry in astroglial cells in the marginal zone of rat neocortex

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Rabea eMüller

2013-03-01

Full Text Available In cells cultured from neocortex of newborn rats, phosphoinositide-3-kinases of class I regulate the DNA synthesis in a subgroup of astroglial cells. We have studied the location of these cells as well as the kinase isoforms which facilitate the S phase entry. Using dominant negative isoforms as well as selective pharmacological inhibitors we quantified S phase entry by nuclear labeling with bromodeoxyuridine. Only in astroglial cells harvested from the marginal zone of the neocortex inhibition of phosphoinositide-3-kinases reduced the nuclear labeling with bromodeoxyuridine, indicating that neocortical astroglial cells differ in the regulation of proliferation. The two kinase isoforms p110 and p110were essential for S phase entry. p110 diminished the level of the p27Kip1 which inactivates the complex of cyclin E and CDK2 necessary for entry into the S phase. p110phosphorylated and inhibited glycogen synthase kinase-3which can prevent S-phase entry. Taken together, both isoforms mediated S phase in a subgroup of neocortical astroglial cells and acted via distinct pathways.

The use of microwave tissue fixation to demonstrate the in vivo phosphorylation of an acidic 80,000 molecular weight protein in the rat neocortex following treatment with soman

International Nuclear Information System (INIS)

Mobley, P.L.; Gonzalez, N.E.

1991-01-01

Studies were conducted to determine if soman, a cholinesterase inhibitor, could activate the protein kinase C system in the rat neocortex. Using microwave radiation for rapid tissue fixation, it was demonstrated that treatment with soman increased 32 P incorporation into an acidic 80,000 molecular weight, heat-stable protein in vivo. Based on relative molecular weight and isoelectric point this protein appears to be identical to a protein identified as a substrate for protein kinase C. Additionally, a protein of the same molecular weight and isoelectric point could be phosphorylated in tissue slices prepared from the neocortex by cholinergic dependent mechanisms. Also, treatment with soman decreased protein kinase C in the soluble fraction of this brain region; however, no corresponding increase was observed in the particulate fraction. These results suggest that soman can activate protein kinase C in vivo, and demonstrate the utility of using microwave tissue fixation to study protein phosphorylation events in vivo

The use of microwave tissue fixation to demonstrate the in vivo phosphorylation of an acidic 80,000 molecular weight protein in the rat neocortex following treatment with soman

Energy Technology Data Exchange (ETDEWEB)

Mobley, P.L.; Gonzalez, N.E. (Univ. of Texas Health Science Center, San Antonio (United States))

1991-01-01

Studies were conducted to determine if soman, a cholinesterase inhibitor, could activate the protein kinase C system in the rat neocortex. Using microwave radiation for rapid tissue fixation, it was demonstrated that treatment with soman increased {sup 32}P incorporation into an acidic 80,000 molecular weight, heat-stable protein in vivo. Based on relative molecular weight and isoelectric point this protein appears to be identical to a protein identified as a substrate for protein kinase C. Additionally, a protein of the same molecular weight and isoelectric point could be phosphorylated in tissue slices prepared from the neocortex by cholinergic dependent mechanisms. Also, treatment with soman decreased protein kinase C in the soluble fraction of this brain region; however, no corresponding increase was observed in the particulate fraction. These results suggest that soman can activate protein kinase C in vivo, and demonstrate the utility of using microwave tissue fixation to study protein phosphorylation events in vivo.

Development and application of the Chinese adult female computational phantom Rad-HUMAN

International Nuclear Information System (INIS)

Wu, Yican; Cheng, Mengyun; Wang, Wen; Fan, Yanchang; Zhao, Kai; He, Tao; Pei, Xi; Shang, Leiming; Chen, Chaobin; Long, Pengcheng; Cao, Ruifen; Wang, Guozhong; Zhou, Shaoheng; Yu, Shengpeng; Hu, Liqin; Zeng, Q.

2013-01-01

Rad-HUMAN is a whole-body numerical phantom of a Chinese adult woman which contains 46 organs and tissues and was created by MCAM6 software using the color photographs of the Chinese Visible Human dataset. This dataset was obtained from a 22-year old Chinese female cadaver judged to represent normal human anatomy as much as possible. The density and elemental composition recommended in the ICRP Publication 89 and in the ICRU report 44 were assigned to the organ and tissue in Rad-HUMAN for radiation protection purpose. The last step was to implement the anatomical data into a Monte Carlo code. Rad-HUMAN contains more than 28.8 billion tiny volume units, which produces an accurately whole-body numerical phantom of a Chinese adult female

A method for unit recording in the lumbar spinal cord during locomotion of the conscious adult rat

DEFF Research Database (Denmark)

Berg, Rune W; Chen, Ming-Teh; Huang, Hsueh-Chen

2009-01-01

Extracellular recordings from single units in the brain, for example the neocortex, have proven feasible in moving, awake rats, but have not yet been possible in the spinal cord. Single-unit activity during locomotor-like activity in reduced preparations from adult cats and rats have provided...... valuable insights for the development of hypotheses about the organization of functional networks in the spinal cord. However, since reduced preparations could result in spurious conclusions, it is crucial to test these hypotheses in animals that are awake and behaving. Furthermore, unresolved issues...

The potential pitfalls of studying adult sex ratios at aggregate levels in humans.

Science.gov (United States)

Pollet, Thomas V; Stoevenbelt, Andrea H; Kuppens, Toon

2017-09-19

Human adult sex ratios have been studied extensively across the biological and social sciences. While several studies have examined adult sex ratio effects in a multilevel perspective, many studies have focused on effects at an aggregated level only. In this paper, we review some key issues relating to such analyses. We address not only nation-level analyses, but also aggregation at lower levels, to investigate whether these issues extend to lower levels of aggregation. We illustrate these issues with novel databases covering a broad range of variables. Specifically, we discuss distributional issues with aggregated measures of adult sex ratio, significance testing, and statistical non-independence when using aggregate data. Firstly, we show that there are severe distributional issues with national adult sex ratio, such as extreme cases. Secondly, we demonstrate that many 'meaningless' variables are significantly correlated with adult sex ratio (e.g. the max. elevation level correlates with sex ratio at US state level). Finally, we re-examine associations between adult sex ratios and teenage fertility and find no robust evidence for an association at the aggregate level. Our review highlights the potential issues of using aggregate data on adult sex ratios to test hypotheses from an evolutionary perspective in humans.This article is part of the themed issue 'Adult sex ratios and reproductive decisions: a critical re-examination of sex differences in human and animal societies'. © 2017 The Author(s).

Expression of the homeobox genes OTX2 and OTX1 in the early developing human brain

DEFF Research Database (Denmark)

Larsen, Karen B; Lutterodt, Melissa C; Møllgård, Kjeld

2010-01-01

, and choroid plexus, with a minor expression in the basal telencephalon. The expression of OTX2 in the hippocampal anlage was strong, with no expression in the adjacent neocortex. Contrarily, the OTX1 expression was predominantly located in the proliferative zones of the neocortex. At later stages, the OTX2...... in the neocortex, and OTX2 in the archicortex, diencephalon, rostral brain stem, and cerebellum....

Linking adult hippocampal neurogenesis with human physiology and disease.

Science.gov (United States)

Bowers, Megan; Jessberger, Sebastian

2016-07-01

We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Induction of GLUT-1 protein in adult human skeletal muscle fibers

DEFF Research Database (Denmark)

Gaster, M; Franch, J; Staehr, P

2000-01-01

Prompted by our recent observations that GLUT-1 is expressed in fetal muscles, but not in adult muscle fibers, we decided to investigate whether GLUT-1 expression could be reactivated. We studied different stimuli concerning their ability to induce GLUT-1 expression in mature human skeletal muscle...... fibers. Metabolic stress (obesity, non-insulin-dependent diabetes mellitus), contractile activity (training), and conditions of de- and reinnervation (amyotrophic lateral sclerosis) could not induce GLUT-1 expression in human muscle fibers. However, regenerating muscle fibers in polymyositis expressed...... GLUT-1. In contrast to GLUT-1, GLUT-4 was expressed in all investigated muscle fibers. Although the significance of GLUT-1 in adult human muscle fibers appears limited, GLUT-1 may be of importance for the glucose supplies in immature and regenerating muscle....

Time organization of frontal-motor cortex interneuron interactions in the cat neocortex in conditions of different levels of food motivation.

Science.gov (United States)

Merzhanova, G Kh; Dolbakyan, E E

1997-01-01

Studies were carried out in conscious cats with recording of multicellular activity in moderate hunger and after 24-h food deprivation. Cross-correlation analysis was used to assess statistical interneuron interactions between closely-located neurons in the frontal and sensorimotor regions of the neocortex (local networks), and between the cells of these regions (distributed networks). One-day food deprivation increased the number of interactions formed within both local and distributed neuron networks. Increases in intercortical connections between the frontal and motor regions was seen at all time intervals studied (0-100 msec), though the most significant changes occurred at time intervals of up to 30 msec.

The evolution of the brain, the human nature of cortical circuits and intellectual creativity

Directory of Open Access Journals (Sweden)

Javier eDeFelipe

2011-05-01

Full Text Available The tremendous expansion and the differentiation of the neocortex constitute two major events in the evolution of the mammalian brain. The increase in size and complexity of our brains opened the way to a spectacular development of cognitive and mental skills. This expansion during evolution facilitated the addition of archetypical microcircuits, which increased the complexity of the human brain and contributed to its uniqueness. However, fundamental differences even exist between distinct mammalian species. Here, we shall discuss the issue of our humanity from a neurobiological and historical perspective.

Mapping the nanostructures in human adult and baby tooth enamel

International Nuclear Information System (INIS)

Low, I.M.; Mahmood, U.; Duraman, N.

2005-01-01

This paper investigates and compares the variations in crystal structure, composition, and nanostructures within the human adult and deciduous teeth. The similarities and differences in the nanostructure of both types of teeth are highlighted and discussed. (author)

The nutrition intervention improved adult human capital and economic productivity.

Science.gov (United States)

Martorell, Reynaldo; Melgar, Paul; Maluccio, John A; Stein, Aryeh D; Rivera, Juan A

2010-02-01

This article reviews key findings about the long-term impact of a nutrition intervention carried out by the Institute of Nutrition of Central America and Panama from 1969 to 1977. Results from follow-up studies in 1988-89 and 2002-04 show substantial impact on adult human capital and economic productivity. The 1988-89 study showed that adult body size and work capacity increased for those provided improved nutrition through age 3 y, whereas the 2002-04 follow-up showed that schooling was increased for women and reading comprehension and intelligence increased in both men and women. Participants were 26-42 y of age at the time of the 2002-04 follow-up, facilitating the assessment of economic productivity. Wages of men increased by 46% in those provided with improved nutrition through age 2 y. Findings for cardiovascular disease risk factors were heterogeneous; however, they suggest that improved nutrition in early life is unlikely to increase cardiovascular disease risk later in life and may indeed lower risk. In conclusion, the substantial improvement in adult human capital and economic productivity resulting from the nutrition intervention provides a powerful argument for promoting improvements in nutrition in pregnant women and young children.

Period concatenation underlies interactions between gamma and beta rhythms in neocortex

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Anita K Roopun

2008-04-01

Full Text Available The neocortex generates rhythmic electrical activity over a frequency range covering many decades. Specific cognitive and motor states are associated with oscillations in discrete frequency bands within this range, but it is not known whether interactions and transitions between distinct frequencies are of functional importance. When coexpressed rhythms have frequencies that differ by a factor of two or more interactions can be seen in terms of phase synchronization. Larger frequency differences can result in interactions in the form of nesting of faster frequencies within slower ones by a process of amplitude modulation. It is not known how coexpressed rhythms, whose frequencies differ by less than a factor of two may interact. Here we show that two frequencies (gamma – 40 Hz and beta2 – 25 Hz, coexpressed in superficial and deep cortical laminae with low temporal interaction, can combine to generate a third frequency (beta1 – 15 Hz showing strong temporal interaction. The process occurs via period concatenation, with basic rhythm-generating microcircuits underlying gamma and beta2 rhythms forming the building blocks of the beta1 rhythm by a process of addition. The mean ratio of adjacent frequency components was a constant – approximately the golden mean – which served to both minimize temporal interactions, and permit multiple transitions, between frequencies. The resulting temporal landscape may provide a framework for multiplexing – parallel information processing on multiple temporal scales.

Monocular Visual Deprivation Suppresses Excitability in Adult Human Visual Cortex

DEFF Research Database (Denmark)

Lou, Astrid Rosenstand; Madsen, Kristoffer Hougaard; Paulson, Olaf Bjarne

2011-01-01

The adult visual cortex maintains a substantial potential for plasticity in response to a change in visual input. For instance, transcranial magnetic stimulation (TMS) studies have shown that binocular deprivation (BD) increases the cortical excitability for inducing phosphenes with TMS. Here, we...... of visual deprivation has a substantial impact on experience-dependent plasticity of the human visual cortex.......The adult visual cortex maintains a substantial potential for plasticity in response to a change in visual input. For instance, transcranial magnetic stimulation (TMS) studies have shown that binocular deprivation (BD) increases the cortical excitability for inducing phosphenes with TMS. Here, we...... employed TMS to trace plastic changes in adult visual cortex before, during, and after 48 h of monocular deprivation (MD) of the right dominant eye. In healthy adult volunteers, MD-induced changes in visual cortex excitability were probed with paired-pulse TMS applied to the left and right occipital cortex...

Populations of subplate and interstitial neurons in fetal and adult human telencephalon.

Science.gov (United States)

Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša

2010-10-01

In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular

The potential pitfalls of studying adult sex ratios at aggregate levels in humans

NARCIS (Netherlands)

Pollet, Thomas V.; Stoevenbelt, Andrea H.; Kuppens, Toon

2017-01-01

Human adult sex ratios have been studied extensively across the biological and social sciences. While several studies have examined adult sex ratio effects in a multilevel perspective, many studies have focused on effects at an aggregated level only. In this paper, we review some key issues relating

Creativity, Social Justice and Human Rights within Adult Education

Science.gov (United States)

Brown, Susannah

2015-01-01

In this paper, the author describes philosophical concepts of adult learning and their application as integrated with creative problem solving within the context of social justice and human rights. The context is framed by the work of the United Nations (1992) which emphasizes importance of women's roles and creativity in the process of forming a…

Embryonic stem cell-like cells derived from adult human testis

NARCIS (Netherlands)

Mizrak, S. C.; Chikhovskaya, J. V.; Sadri-Ardekani, H.; van Daalen, S.; Korver, C. M.; Hovingh, S. E.; Roepers-Gajadien, H. L.; Raya, A.; Fluiter, K.; de Reijke, Th M.; de la Rosette, J. J. M. C. H.; Knegt, A. C.; Belmonte, J. C.; van der Veen, F.; de rooij, D. G.; Repping, S.; van Pelt, A. M. M.

2010-01-01

Given the significant drawbacks of using human embryonic stem (hES) cells for regenerative medicine, the search for alternative sources of multipotent cells is ongoing. Studies in mice have shown that multipotent ES-like cells can be derived from neonatal and adult testis. Here we report the

CD4+ T-Lymphocytes cell counts in adults with human ...

African Journals Online (AJOL)

Objectives: To evaluate the CD4+ cell counts in adults with human immunodeficiency virus (HIV) infections presenting at the medical department of the Federal Medical Centre, Ido-Ekiti, Nigeria. Methods: This study was carried out at the medical department of the Federal Medical Centre (FMC), Ido-Ekiti, Nigeria, in the ...

Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential

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Cindy J.M. Loomans

2018-03-01

Full Text Available Summary: Generating an unlimited source of human insulin-producing cells is a prerequisite to advance β cell replacement therapy for diabetes. Here, we describe a 3D culture system that supports the expansion of adult human pancreatic tissue and the generation of a cell subpopulation with progenitor characteristics. These cells display high aldehyde dehydrogenase activity (ALDHhi, express pancreatic progenitors markers (PDX1, PTF1A, CPA1, and MYC, and can form new organoids in contrast to ALDHlo cells. Interestingly, gene expression profiling revealed that ALDHhi cells are closer to human fetal pancreatic tissue compared with adult pancreatic tissue. Endocrine lineage markers were detected upon in vitro differentiation. Engrafted organoids differentiated toward insulin-positive (INS+ cells, and circulating human C-peptide was detected upon glucose challenge 1 month after transplantation. Engrafted ALDHhi cells formed INS+ cells. We conclude that adult human pancreatic tissue has potential for expansion into 3D structures harboring progenitor cells with endocrine differentiation potential. : In the context of β cell replacement therapy for diabetes, de Koning and colleagues describe a 3D culture platform that supports ex vivo expansion of human pancreatic tissue as organoids. These organoids harbor a subpopulation of ALDHhi cells that display proliferative capacity and can differentiate to an endocrine fate. Keywords: pancreas, organoid, human, ALDH, endocrine differentiation, beta cells, insulin, progenitor, fetal, diabetes

Self-Control and Impulsiveness in Nondieting Adult Human Females: Effects of Visual Food Cues and Food Deprivation

Science.gov (United States)

Forzano, Lori-Ann B.; Chelonis, John J.; Casey, Caitlin; Forward, Marion; Stachowiak, Jacqueline A.; Wood, Jennifer

2010-01-01

Self-control can be defined as the choice of a larger, more delayed reinforcer over a smaller, less delayed reinforcer, and impulsiveness as the opposite. Previous research suggests that exposure to visual food cues affects adult humans' self-control. Previous research also suggests that food deprivation decreases adult humans' self-control. The…

Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases

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He Liu

2016-01-01

Full Text Available Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and brain tumors.

Periodontitis and oral human papillomavirus infection among Hispanic adults

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Ana Patricia Ortiz

2018-06-01

Full Text Available Introduction: Research on the association between periodontitis and oral human papilloma virus (HPV infection is inconsistent. The cross-sectional association of severe periodontitis with oral HPV infection was investigated in a sample of Hispanic adults. Methods: Data from the 2014–2016 San Juan Overweight Adults Longitudinal Study (n = 740 was analyzed. Periodontitis assessment and self-collection of oral HPV samples followed the National Health and Nutrition Examination Survey methodology. Periodontitis was defined using the Centers of Disease Control and Prevention/American Academy of Periodontology definition. HPV typing was performed using polymerase chain reaction. Multivariate logistic regression models were used to calculate odds ratios (ORs and 95% confidence intervals (CIs. Results: 5.7% of participants had oral HPV infection and 20.3% had severe periodontitis. Adults with severe periodontitis had higher odds of oral HPV infection than those with none/mild disease (OR=2.9, 95% CI: 1.0–8.4, p < 0.05 in multivariable analysis. Adults with clinical attachment loss≥ 7 mm and pocket depth PD≥ 6 mm had 2- to 3-fold higher odds of HPV infection. Conclusions: Severe periodontitis was positively associated to oral HPV infection. Longitudinal evaluation of periodontal inflammation's role in acquisition and persistence of oral HPV infection is needed, as periodontitis screening could identify individuals at increased risk of HPV-related oral malignancies. Keywords: Periodontitis, Oral HPV, Hispanics, Adults, Oral health, Puerto Rico

Layer- and Cell Type-Specific Modulation of Excitatory Neuronal Activity in the Neocortex

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Gabriele Radnikow

2018-01-01

Full Text Available From an anatomical point of view the neocortex is subdivided into up to six layers depending on the cortical area. This subdivision has been described already by Meynert and Brodmann in the late 19/early 20. century and is mainly based on cytoarchitectonic features such as the size and location of the pyramidal cell bodies. Hence, cortical lamination is originally an anatomical concept based on the distribution of excitatory neuron. However, it has become apparent in recent years that apart from the layer-specific differences in morphological features, many functional properties of neurons are also dependent on cortical layer or cell type. Such functional differences include changes in neuronal excitability and synaptic activity by neuromodulatory transmitters. Many of these neuromodulators are released from axonal afferents from subcortical brain regions while others are released intrinsically. In this review we aim to describe layer- and cell-type specific differences in the effects of neuromodulator receptors in excitatory neurons in layers 2–6 of different cortical areas. We will focus on the neuromodulator systems using adenosine, acetylcholine, dopamine, and orexin/hypocretin as examples because these neuromodulator systems show important differences in receptor type and distribution, mode of release and functional mechanisms and effects. We try to summarize how layer- and cell type-specific neuromodulation may affect synaptic signaling in cortical microcircuits.

Attitudes of Korean adults towards human dignity: a Q methodology approach.

Science.gov (United States)

Jo, Kae Hwa; An, Gyeong-Ju; Doorenbos, Ardith Z

2012-06-01

The aim of this study was to identify the perceived attitudes of Korean adults towards human dignity in order to determine the relationship of human dignity to its social and cultural background. The Q methodology research technique was used to explore perceived attitude typology on the basis of the respondents' ranking order for different statements. A convenience sampling method was used to select 40 Korean adults who were interested in human dignity to create statements. From the questionnaires, in-depth interviews, and a literature review, a total of 158 statements was obtained. The final 34 Q samples were selected from a review by two nursing professors and a Q methodology expert. Moreover, 38 respondents participated as P samples by sorting 34 Q statements on a nine-point normal distribution scale. The data were analyzed by using the QUANL software package. The following four types of attitudes about human dignity were identified in Korea: a happiness-oriented-self-pursuit type, relationship-oriented-self-recognition type, reflection-oriented-self-unification type, and discrimination-oriented-self-maintenance type. The results indicate that approaches to developing human dignity education need to take this typology into account and the characteristics of the participants who fall into each category. These results provide general guidelines to understand Korean values for professional practice in various healthcare settings. © 2011 The Authors. Japan Journal of Nursing Science © 2011 Japan Academy of Nursing Science.

Acceptance and Attitudes Toward a Human-like Socially Assistive Robot by Older Adults.

Science.gov (United States)

Louie, Wing-Yue Geoffrey; McColl, Derek; Nejat, Goldie

2014-01-01

Recent studies have shown that cognitive and social interventions are crucial to the overall health of older adults including their psychological, cognitive, and physical well-being. However, due to the rapidly growing elderly population of the world, the resources and people to provide these interventions is lacking. Our work focuses on the use of social robotic technologies to provide person-centered cognitive interventions. In this article, we investigate the acceptance and attitudes of older adults toward the human-like expressive socially assistive robot Brian 2.1 in order to determine if the robot's human-like assistive and social characteristics would promote the use of the robot as a cognitive and social interaction tool to aid with activities of daily living. The results of a robot acceptance questionnaire administered during a robot demonstration session with a group of 46 elderly adults showed that the majority of the individuals had positive attitudes toward the socially assistive robot and its intended applications.

The mandibular angles of dry adult human mandibles from north ...

African Journals Online (AJOL)

The mandibular angles of dry adult human mandibles from north-eastern arid zone of Nigeria. EF Mbajiorgu, AU Ekanem. Abstract. (Central African Journal of Medicine: 2002 48 (1-2): 9-13). http://dx.doi.org/10.4314/cajm.v48i1.8417 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians ...

Examination of Oral Microbiota Diversity in Adults and Older Adults as an Approach to Prevent Spread of Risk Factors for Human Infections.

Science.gov (United States)

Zawadzki, Paweł J; Perkowski, Konrad; Padzik, Marcin; Mierzwińska-Nastalska, Elżbieta; Szaflik, Jacek P; Conn, David Bruce; Chomicz, Lidia

2017-01-01

The oral cavity environment may be colonized by polymicrobial communities with complex, poorly known interrelations. The aim of this study was to determine oral microbiota diversity in order to prevent the spread of infectious microorganisms that are risk factors for human health complications in patients requiring treatment due to various disabilities. The study examined Polish adults aged between 40 and 70 years; parasitological, microbiological, and mycological data collected before treatment were analyzed. The diversity of oral microbiota, including relatively high prevalences of some opportunistic, potentially pathogenic strains of bacteria, protozoans, and fungi detected in the patients analyzed, may result in increasing risk of disseminated infections from the oral cavity to neighboring structures and other organs. Increasing ageing of human populations is noted in recent decades in many countries, including Poland. The growing number of older adults with different oral health disabilities, who are more prone to development of oral and systemic pathology, is an increasing medical problem. Results of this retrospective study showed the urgent need to pay more attention to the pretreatment examination of components of the oral microbiome, especially to the strains, which are etiological agents of human opportunistic infections and are particularly dangerous for older adults.

Topographic variation in redifferentiation capacity of chondrocytes in the adult human knee joint.

Science.gov (United States)

Stenhamre, H; Slynarski, K; Petrén, C; Tallheden, T; Lindahl, A

2008-11-01

The aim of this study was to investigate the topographic variation in matrix production and cell density in the adult human knee joint. Additionally, we have examined the redifferentiation potential of chondrocytes expanded in vitro from the different locations. Full thickness cartilage-bone biopsies were harvested from seven separate anatomical locations of healthy knee joints from deceased adult human donors. Chondrocytes were isolated, expanded in vitro and redifferentiated in a pellet mass culture. Biochemical analysis of total collagen, proteoglycans and cellular content as well as histology and immunohistochemistry were performed on biopsies and pellets. In the biochemical analysis of the biopsies, we found lower proteoglycan to collagen (GAG/HP) ratio in the non-weight bearing (NWB) areas compared to the weight bearing (WB) areas. The chondrocytes harvested from different locations in femur showed a significantly better attachment and proliferation ability as well as good post-expansion chondrogenic capacity in pellet mass culture compared with the cells harvested from tibia. These results demonstrate that there are differences in extra cellular content within the adult human knee in respect to GAG/HP ratio. Additionally, the data show that clear differences between chondrocytes harvested from femur and tibia from healthy human knee joints exist and that the differences are not completely abolished during the process of de- and redifferentiation. These findings emphasize the importance of the understanding of topographic variation in articular cartilage biology when approaching new cartilage repair strategies.

The influence of rAAV2-mediated SOX2 delivery into neonatal and adult human RPE cells; a comparative study.

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Ezati, Razie; Etemadzadeh, Azadeh; Soheili, Zahra-Soheila; Samiei, Shahram; Ranaei Pirmardan, Ehsan; Davari, Malihe; Najafabadi, Hoda Shams

2018-02-01

Cell replacement is a promising therapy for degenerative diseases like age-related macular degeneration (AMD). Since the human retina lacks regeneration capacity, much attention has been directed toward persuading for cells that can differentiate into retinal neurons. In this report, we have investigated reprogramming of the human RPE cells and concerned the effect of donor age on the cellular fate as a critical determinant in reprogramming competence. We evaluated the effect of SOX2 over-expression in human neonatal and adult RPE cells in cultures. The coding region of human SOX2 gene was cloned into adeno-associated virus (AAV2) and primary culture of human neonatal/adult RPE cells were infected by recombinant virus. De-differentiation of RPE to neural/retinal progenitor cells was investigated by quantitative real-time PCR and ICC for neural/retinal progenitor cells' markers. Gene expression analysis showed 80-fold and 12-fold over-expression for SOX2 gene in infected neonatal and adult hRPE cells, respectively. The fold of increase for Nestin in neonatal and adult hRPE cells was 3.8-fold and 2.5-fold, respectively. PAX6 expression was increased threefold and 2.5-fold in neonatal/adult treated cultures. Howbeit, we could not detect rhodopsin, and CHX10 expression in neonatal hRPE cultures and expression of rhodopsin in adult hRPE cells. Results showed SOX2 induced human neonatal/adult RPE cells to de-differentiate toward retinal progenitor cells. However, the increased number of PAX6, CHX10, Thy1, and rhodopsin positive cells in adult hRPE treated cultures clearly indicated the considerable generation of neuro-retinal terminally differentiated cells. © 2017 Wiley Periodicals, Inc.

Gonadotropin-releasing hormone immunoreactivity in the adult and fetal human olfactory system.

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Kim, K H; Patel, L; Tobet, S A; King, J C; Rubin, B S; Stopa, E G

1999-05-01

Studies in fetal brain tissue of rodents, nonhuman primates and birds have demonstrated that cells containing gonadotropin-releasing hormone (GnRH) migrate from the olfactory placode across the nasal septum into the forebrain. The purpose of this study was to examine GnRH neurons in components of the adult and fetal human olfactory system. In the adult human brain (n=4), immunoreactive GnRH was evident within diffusely scattered cell bodies and processes in the olfactory bulb, olfactory nerve, olfactory cortex, and nervus terminalis located on the anterior surface of the gyrus rectus. GnRH-immunoreactive structures showed a similar distribution in 20-week human fetal brains (n=2), indicating that the migration of GnRH neurons is complete at this time. In 10-11-week fetal brains (n=2), more cells were noted in the nasal cavity than in the brain. Our data are consistent with observations made in other species, confirming olfactory derivation and migration of GnRH neurons into the brain from the olfactory placode. Copyright 1999 Elsevier Science B.V.

Early reversal cells in adult human bone remodeling

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Abdelgawad, Mohamed Essameldin; Delaissé, Jean-Marie; Hinge, Maja

2016-01-01

The mechanism coupling bone resorption and formation is a burning question that remains incompletely answered through the current investigations on osteoclasts and osteoblasts. An attractive hypothesis is that the reversal cells are likely mediators of this coupling. Their nature is a big matter...... of debate. The present study performed on human cancellous bone is the first one combining in situ hybridization and immunohistochemistry to demonstrate their osteoblastic nature. It shows that the Runx2 and CD56 immunoreactive reversal cells appear to take up TRAcP released by neighboring osteoclasts....... Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone...

Targeted Ablation and Reorganization of the Principal Preplate Neurons and Their Neuroblasts Identified by Golli Promoter Transgene Expression in the Neocortex of Mice

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Yuan-Yun Xie

2009-10-01

Full Text Available The present study delineates the cellular responses of dorsal pallium to targeted genetic ablation of the principal preplate neurons of the neocortex. Ganciclovir treatment during prenatal development (E11-E13; where E is embryonic day of mice selectively killed cells with shared S-phase vulnerability and targeted expression of a GPT [golli promoter transgene, linked to HSV-TK (herpes simplex virus-thymidine kinase, τ-eGFP (τ-enhanced green fluorescent protein and lacZ (lacZ galactosidase reporters] localized in preplate neurons. Morphogenetic fates of attacked neurons and neuroblasts, and their successors, were assessed by multiple labelling in time-series comparisons between ablated (HSV-TK+/0 and control (HSV-TK0/0 littermates. During ablation generation, neocortical growth was suppressed, and compensatory reorganization of non-GPT ventricular zone progenitors of dorsal pallium produced replacements for killed GPT neuroblasts. Replacement and surviving GPT neuroblasts then produced replacements for killed GPT neurons. Near-normal restoration of their complement delayed the settlement of GPT neurons into the reconstituted preplate, which curtailed the outgrowth of pioneer corticofugal axons. Based on this evidence, we conclude that specific cell killing in ablated mice can eliminate a major fraction of GPT neurons, with insignificant bystander killing. Also, replacement GPT neurons in ablated mice originate exclusively by proliferation from intermediate progenitor GPT neuroblasts, whose complement is maintained by non-GPT progenitors for inductive regulation of the total complement of GPT neurons. Finally, GPT neurons in both normal and ablated mice meet all morphogenetic criteria, including the ‘outside-in’ vertical gradient of settlement, presently used to identify principal preplate neurons. In ablated mice, delayed organization of these neurons desynchronizes and isolates developing neocortex from the rest of the brain, and

The Longitudinal Study of Aging in Human Young Adults: Knowledge Gaps and Research Agenda.

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Moffitt, Terrie E; Belsky, Daniel W; Danese, Andrea; Poulton, Richie; Caspi, Avshalom

2017-02-01

To prevent onset of age-related diseases and physical and cognitive decline, interventions to slow human aging and extend health span must eventually be applied to people while they are still young and healthy. Yet most human aging research examines older adults, many with chronic disease, and little is known about aging in healthy young humans. This article explains how this knowledge gap is a barrier to extending health span and puts forward the case that geroscience should invest in researching the pace of aging in young adults. As one illustrative example, we describe an initial effort to study the pace of aging in a young-adult birth cohort by using repeated waves of biomarkers collected across the third and fourth decades to quantify the pace of coordinated physiological deterioration across multiple organ systems (eg, pulmonary, periodontal, cardiovascular, renal, hepatic, metabolic, and immune function). Findings provided proof of principle that it is possible to quantify individual variation in the pace of aging in young adults still free of age-related diseases. This article articulates research needs to improve longitudinal measurement of the pace of aging in young people, to pinpoint factors that slow or speed the pace of aging, to compare pace of aging against genomic clocks, to explain slow-aging young adults, and to apply pace of aging in preventive clinical trials of antiaging therapies. This article puts forward a research agenda to fill the knowledge gap concerning lifelong causes of aging. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults

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Larsen, Nadja; Vogensen, Finn Kvist; van der Berg, Franciscus Winfried J

2010-01-01

. Methods and Findings The study included 36 male adults with a broad range of age and body-mass indices (BMIs), among which 18 subjects were diagnosed with diabetes type 2. The fecal bacterial composition was investigated by real-time quantitative PCR (qPCR) and in a subgroup of subjects (N = 20) by tag...... = 0.04). Conclusions The results of this study indicate that type 2 diabetes in humans is associated with compositional changes in intestinal microbiota. The level of glucose tolerance should be considered when linking microbiota with metabolic diseases such as obesity and developing strategies......Background Recent evidence suggests that there is a link between metabolic diseases and bacterial populations in the gut. The aim of this study was to assess the differences between the composition of the intestinal microbiota in humans with type 2 diabetes and non-diabetic persons as control...

Mental rotation and the human body: Children's inflexible use of embodiment mirrors that of adults.

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Krüger, Markus; Ebersbach, Mirjam

2017-12-25

Adults' mental rotation performance with body-like stimuli is enhanced if these stimuli are anatomically compatible with a human body, but decreased by anatomically incompatible stimuli. In this study, we investigated these effects for kindergartners and first-graders: When asked to mentally rotate cube configurations attached with human body parts in an anatomically compatible way, allowing for the projection of a human body, children performed better than with pure cube combinations. By contrast, when body parts were attached in an anatomically incompatible way, disallowing the projection of a human body, children performed worse than with pure combinations. This experiment is of specific interest against the background of two different theoretical approaches concerning imagery and the motor system in development: One approach assumes an increasing integration of motor processes and imagery over time that enables older children and adults to requisition motor resources for imagery processes, while the other postulates that imagery stems from early sensorimotor processes in the first place, and is disentangled from it over time. The finding that children of the two age groups tested show exactly the same effects as adults when mentally rotating anatomically compatible and incompatible stimuli is interpreted in favour of the latter approach. Statement of contribution What is already known on this subject? In mental rotation, adults perform better when rotating anatomically possible stimuli as compared to rotating standard cube combinations. Performance is worse when rotating anatomically impossible stimuli. What does this study add? The present study shows that children's mental transformations mirror those of adults in these respects. In case of the anatomically impossible stimuli, this highlights an inflexible use of embodiment in both age groups. This is in line with the Piagetian assumption of imagery being based on sensorimotor processes. © 2017 The British

Regulated gene expression in cultured type II cells of adult human lung.

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Ballard, Philip L; Lee, Jae W; Fang, Xiaohui; Chapin, Cheryl; Allen, Lennell; Segal, Mark R; Fischer, Horst; Illek, Beate; Gonzales, Linda W; Kolla, Venkatadri; Matthay, Michael A

2010-07-01

Alveolar type II cells have multiple functions, including surfactant production and fluid clearance, which are critical for lung function. Differentiation of type II cells occurs in cultured fetal lung epithelial cells treated with dexamethasone plus cAMP and isobutylmethylxanthine (DCI) and involves increased expression of 388 genes. In this study, type II cells of human adult lung were isolated at approximately 95% purity, and gene expression was determined (Affymetrix) before and after culturing 5 days on collagen-coated dishes with or without DCI for the final 3 days. In freshly isolated cells, highly expressed genes included SFTPA/B/C, SCGB1A, IL8, CXCL2, and SFN in addition to ubiquitously expressed genes. Transcript abundance was correlated between fetal and adult cells (r = 0.88), with a subset of 187 genes primarily related to inflammation and immunity that were expressed >10-fold higher in adult cells. During control culture, expression increased for 8.1% of expressed genes and decreased for approximately 4% including 118 immune response and 10 surfactant-related genes. DCI treatment promoted lamellar body production and increased expression of approximately 3% of probed genes by > or =1.5-fold; 40% of these were also induced in fetal cells. Highly induced genes (> or =10-fold) included PGC, ZBTB16, DUOX1, PLUNC, CIT, and CRTAC1. Twenty-five induced genes, including six genes related to surfactant (SFTPA/B/C, PGC, CEBPD, and ADFP), also had decreased expression during control culture and thus are candidates for hormonal regulation in vivo. Our results further define the adult human type II cell molecular phenotype and demonstrate that a subset of genes remains hormone responsive in cultured adult cells.

Statistical theory of synaptic connectivity in the neocortex

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Escobar, Gina

Learning and long-term memory rely on plasticity of neural circuits. In adult cerebral cortex plasticity can be mediated by modulation of existing synapses and structural reorganization of circuits through growth and retraction of dendritic spines. In the first part of this thesis, we describe a theoretical framework for the analysis of spine remodeling plasticity. New synaptic contacts appear in the neuropil where gaps between axonal and dendritic branches can be bridged by dendritic spines. Such sites are termed potential synapses. We derive expressions for the densities of potential synapses in the neuropil. We calculate the ratio of actual to potential synapses, called the connectivity fraction, and use it to find the number of structurally different circuits attainable with spine remodeling. These parameters are calculated in four systems: mouse occipital cortex, rat hippocampal area CA1, monkey primary visual (V1), and human temporal cortex. The neurogeometric results indicate that a dendritic spine can choose among an average of 4-7 potential targets in rodents, while in primates it can choose from 10-20 potential targets. The potential of the neuropil to undergo circuit remodeling is found to be highest in rat CA1 (4.9-6.0 nats/mum 3) and lowest in monkey V1 (0.9-1.0 nats/mum3). We evaluate the lower bound of neuron selectivity in the choice of synaptic partners and find that post-synaptic excitatory neurons in rodents make synaptic contacts with more than 21-30% of pre-synaptic axons encountered with new spine growth. Primate neurons appear to be more selective, making synaptic connections with more than 7-15% of encountered axons. Another plasticity mechanism is included in the second part of this work: long-term potentiation and depression of excitatory synaptic connections. Because synaptic strength is correlated with the size of the synapse, the former can be inferred from the distribution of spine head volumes. To this end we analyze and compare 166

Examination of Oral Microbiota Diversity in Adults and Older Adults as an Approach to Prevent Spread of Risk Factors for Human Infections

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Paweł J. Zawadzki

2017-01-01

Full Text Available The oral cavity environment may be colonized by polymicrobial communities with complex, poorly known interrelations. The aim of this study was to determine oral microbiota diversity in order to prevent the spread of infectious microorganisms that are risk factors for human health complications in patients requiring treatment due to various disabilities. The study examined Polish adults aged between 40 and 70 years; parasitological, microbiological, and mycological data collected before treatment were analyzed. The diversity of oral microbiota, including relatively high prevalences of some opportunistic, potentially pathogenic strains of bacteria, protozoans, and fungi detected in the patients analyzed, may result in increasing risk of disseminated infections from the oral cavity to neighboring structures and other organs. Increasing ageing of human populations is noted in recent decades in many countries, including Poland. The growing number of older adults with different oral health disabilities, who are more prone to development of oral and systemic pathology, is an increasing medical problem. Results of this retrospective study showed the urgent need to pay more attention to the pretreatment examination of components of the oral microbiome, especially to the strains, which are etiological agents of human opportunistic infections and are particularly dangerous for older adults.

SSEA-4 and YKL-40 positive progenitor subtypes in the subventricular zone of developing human neocortex

DEFF Research Database (Denmark)

Brøchner, Christian B; Møllgård, Kjeld

2016-01-01

The glycosphingolipid SSEA-4 and the glycoprotein YKL-40 have both been associated with human embryonic and neural stem cell differentiation. We investigated the distribution of SSEA-4 and YKL-40 positive cells in proliferative zones of human fetal forebrain using immunohistochemistry and double-...

Cell pattern in adult human corneal endothelium.

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Carlos H Wörner

Full Text Available A review of the current data on the cell density of normal adult human endothelial cells was carried out in order to establish some common parameters appearing in the different considered populations. From the analysis of cell growth patterns, it is inferred that the cell aging rate is similar for each of the different considered populations. Also, the morphology, the cell distribution and the tendency to hexagonallity are studied. The results are consistent with the hypothesis that this phenomenon is analogous with cell behavior in other structures such as dry foams and grains in polycrystalline materials. Therefore, its driving force may be controlled by the surface tension and the mobility of the boundaries.

Covert spatial attention is functionally intact in amblyopic human adults

OpenAIRE

Roberts, Mariel; Cymerman, Rachel; Smith, R. Theodore; Kiorpes, Lynne; Carrasco, Marisa

2016-01-01

Certain abnormalities in behavioral performance and neural signaling have been attributed to a deficit of visual attention in amblyopia, a neurodevelopmental disorder characterized by a diverse array of visual deficits following abnormal binocular childhood experience. Critically, most have inferred attention's role in their task without explicitly manipulating and measuring its effects against a baseline condition. Here, we directly investigate whether human amblyopic adults benefit from cov...

Secretory Products of the Human GI Tract Microbiome and Their Potential Impact on Alzheimer's Disease (AD: Detection of Lipopolysaccharide (LPS in AD Hippocampus

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Yuhai Zhao

2017-07-01

Full Text Available Although the potential contribution of the human gastrointestinal (GI tract microbiome to human health, aging, and disease is becoming increasingly acknowledged, the molecular mechanics and signaling pathways of just how this is accomplished is not well-understood. Major bacterial species of the GI tract, such as the abundant Gram-negative bacilli Bacteroides fragilis (B. fragilis and Escherichia coli (E. coli, secrete a remarkably complex array of pro-inflammatory neurotoxins which, when released from the confines of the healthy GI tract, are pathogenic and highly detrimental to the homeostatic function of neurons in the central nervous system (CNS. For the first time here we report the presence of bacterial lipopolysaccharide (LPS in brain lysates from the hippocampus and superior temporal lobe neocortex of Alzheimer's disease (AD brains. Mean LPS levels varied from two-fold increases in the neocortex to three-fold increases in the hippocampus, AD over age-matched controls, however some samples from advanced AD hippocampal cases exhibited up to a 26-fold increase in LPS over age-matched controls. This “Perspectives” paper will further highlight some very recent research on GI tract microbiome signaling to the human CNS, and will update current findings that implicate GI tract microbiome-derived LPS as an important internal contributor to inflammatory degeneration in the CNS.

Building a prototype using Human-Centered design to engage older adults in healthcare decision-making.

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Kumar, Ajit; Maskara, Sanjeev; Chiang, I-Jen

2014-01-01

The prevalence of chronic diseases and disabilities are higher in older adults, which is one of the key factors of rising health care costs. Health care stakeholders wish older adults to take more control of their health to delay the onset of age-related disabilities and chronic diseases. Engaging older adults in their health care decision making would cut down health care costs and prepare a health care system to be more sustainable. We used the Human-Centered Design approach to propose a prototype that more effectively engages older adults in their health care decision-making. Four participants from four different countries - Taiwan, USA, Austria, and Germany; and two facilitators from the USA participated in this study. The participants interviewed a total of four subjects in their respective countries. This study used the Human-Centered Design approach, which embraced three main phases - observation, identification, and ideation. Each phase involved brainstorming, voting, and consensus among participants. This study derived 14 insights, 20 categories, 4 themes, a conceptual framework, some potential solutions, and a prototype. This study showed that older adults could be engaged in their health care decision-making by offering them health care products and services that were user-friendly and technology enabled. A 'gradual change management plan' could assist older adults to adopt technologies more effectively. The health care products and services should be centered on the needs of older adults. Moreover, the possibilities of older adults maintaining control over their own health may rely on proper timing, a personal approach, right products, and services.

Expression pattern of thymosin beta 4 in the adult human liver

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S. Nemolato

2011-09-01

Full Text Available Thymosin beta-4 (Tβ4 is a member of beta-thymosins, a family of small peptides involved in polymerization of G-actin, and in many critical biological processes including apoptosis, cell migration, angiogenesis, and fibrosis. Previous studies in the newborn liver did not reveal any significant reactivity for Tβ4 during the intrauterine life. The aim of the present study was to investigate by immunohistochemistry Tβ4 expression in the adult normal liver. Thirty-five human liver samples, including 11 needle liver biopsies and 24 liver specimens obtained at autopsy, in which no pathological change was detected at the histological examination, were immunostained utilizing an anti-Tβ4 commercial antibody. Tβ4 was detected in the hepatocytes of all adult normal livers examined. A zonation of Tβ4 expression was evident in the vast majority of cases. Immunostaining was preferentially detected in zone 3, while a minor degree of reactivity was detected in periportal hepatocytes (zone 1. At higher power, Tβ4-reactive granules appeared mainly localized at the biliary pole of hepatocytes. In cases with a strong immunostaining, even perinuclear areas and the sinusoidal pole of hepatocytes appeared interested by immunoreactivity for Tβ4. The current work first evidences a strong diffuse expression of Tβ4 in the adult human liver, and adds hepatocytes to the list of human cells able to synthesize large amounts of Tβ4 in adulthood. Moreover, Tβ4 should be added to the liver proteins characterized by a zonate expression pattern, in a descending gradient from the terminal vein to the periportal areas of the liver acinus. Identifying the intimate role played by this peptide intracellularly and extracellularly, in physiology and in different liver diseases, is a major challenge for future research focusing on Tβ4.

A Cell Model to Evaluate Chemical Effects on Adult Human Cardiac Progenitor Cell Differentiation and Function

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Adult cardiac stem cells (CSC) and progenitor cells (CPC) represent a population of cells in the heart critical for its regeneration and function over a lifetime. The impact of chemicals on adult human CSC/CPC differentiation and function is unknown. Research was conducted to dev...

Heterogeneity of D-Serine Distribution in the Human Central Nervous System

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Suzuki, Masataka; Imanishi, Nobuaki; Mita, Masashi; Hamase, Kenji; Aiso, Sadakazu

2017-01-01

D-serine is an endogenous ligand for N-methyl-D-aspartate glutamate receptors. Accumulating evidence including genetic associations of D-serine metabolism with neurological or psychiatric diseases suggest that D-serine is crucial in human neurophysiology. However, distribution and regulation of D-serine in humans are not well understood. Here, we found that D-serine is heterogeneously distributed in the human central nervous system (CNS). The cerebrum contains the highest level of D-serine among the areas in the CNS. There is heterogeneity in its distribution in the cerebrum and even within the cerebral neocortex. The neocortical heterogeneity is associated with Brodmann or functional areas but is unrelated to basic patterns of cortical layer structure or regional expressional variation of metabolic enzymes for D-serine. Such D-serine distribution may reflect functional diversity of glutamatergic neurons in the human CNS, which may serve as a basis for clinical and pharmacological studies on D-serine modulation. PMID:28604057

Astrocitary niches in human adult medulla oblongata.

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Rusu, Mugurel Constantin; Dermengiu, Dan; Loreto, Carla; Motoc, Andrei Gheorghe Marius; Pop, Elena

2013-04-01

Astrocytes are considered as neuromodulators of the CNS. Whereas experimental studies on astrocitary functions are gaining importance, the anatomy of the astrocitary niches in the human CNS has been overlooked. The study was performed on the brainstem of 10 adult cadavers. We aimed to determine astrocitary niches in the human medulla oblongata using immunohistochemical labeling with vimentin and also CD34 immunostaining to accurately diagnose associated microvessels. Niches rich in astrocytes were identified as follows: (a) the superficial layer of astrocytes, ventral and ventrolateral, in the rostral medulla oblongata; (b) the median raphe; (c) medullary nuclei: arcuate nucleus, area postrema, nucleus of the solitary tract; (d) the subependymal zone (SEZ, caudal medulla) and subventricular zone (SVZ, rostral medulla). Astrocytes were scarce in the ventrolateral medulla, and mostly present within the pyramidal tract and the olivary nucleus. Apart from the SEZ and SVZ, the brainstem niches of astrocytes mostly overlap those regions known to perform roles as central respiratory chemoreceptors. The astrocytes of the SEZ and SVZ, which are known as stem cell niches, are related to an increased microvascular density. Copyright © 2012 Elsevier GmbH. All rights reserved.

Analysis of Neural Stem Cells from Human Cortical Brain Structures In Vitro.

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Aleksandrova, M A; Poltavtseva, R A; Marei, M V; Sukhikh, G T

2016-05-01

Comparative immunohistochemical analysis of the neocortex from human fetuses showed that neural stem and progenitor cells are present in the brain throughout the gestation period, at least from week 8 through 26. At the same time, neural stem cells from the first and second trimester fetuses differed by the distribution, morphology, growth, and quantity. Immunocytochemical analysis of neural stem cells derived from fetuses at different gestation terms and cultured under different conditions showed their differentiation capacity. Detailed analysis of neural stem cell populations derived from fetuses on gestation weeks 8-9, 18-20, and 26 expressing Lex/SSEA1 was performed.

Prophylaxis vs. on-demand treatment with Nuwiq(®) (Human-cl rhFVIII) in adults with severe haemophilia A.

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Tiede, A; Oldenburg, J; Lissitchkov, T; Knaub, S; Bichler, J; Manco-Johnson, M J

2016-05-01

Haemophilia A is treated with FVIII, either prophylactically or on demand. Prophylaxis is the gold standard in children and evidence is accumulating in adults. The aim of this analysis was to compare prophylaxis vs. on-demand treatment with Nuwiq(®) (Human-cl rhFVIII), a new-generation rFVIII expressed in a human cell line, in previously treated patients (PTPs) with severe haemophilia A. Data were analysed from two similarly designed, multinational, prospective, open-label studies with similar inclusion and exclusion criteria and comparable patient demographics. Human-cl rhFVIII was administered either prophylactically in a study of 32 adults or on-demand in a study of 22 patients (20 adults and two adolescents). Patients treated prophylactically experienced 36 bleeds compared with 997 bleeds in patients treated on-demand (mean observation periods: 180 and 335 days respectively). Based on a negative binomial regression model, annualized bleeding rate (ABR) during prophylaxis was 2.30 (95% CI: 1.54, 3.44) compared with 57.74 (95% CI: 43.36, 76.91) during on-demand treatment, which equates to a 96% lower ABR during prophylaxis. 'Excellent' or 'good' efficacy in the treatment of bleeds was achieved with Human-cl rhFVIII in 100% of 28 evaluated bleeds during the prophylaxis study and 94.5% of 985 evaluated bleeds during the on-demand study. No inhibitors, treatment-related serious adverse events or severe adverse events were recorded during prophylaxis or or-demand treatment. Prophylaxis with Human-cl rhFVIII reduces recurrent bleeding in adult PTPs with severe haemophilia A and adds further supportive evidence for the benefits of prophylaxis in adults. © 2015 John Wiley & Sons Ltd.

Human Centred Design Considerations for Connected Health Devices for the Older Adult

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Richard P. Harte

2014-06-01

Full Text Available Connected health devices are generally designed for unsupervised use, by non-healthcare professionals, facilitating independent control of the individuals own healthcare. Older adults are major users of such devices and are a population significantly increasing in size. This group presents challenges due to the wide spectrum of capabilities and attitudes towards technology. The fit between capabilities of the user and demands of the device can be optimised in a process called Human Centred Design. Here we review examples of some connected health devices chosen by random selection, assess older adult known capabilities and attitudes and finally make analytical recommendations for design approaches and design specifications.

ABSORPTION-SPECTRA OF HUMAN FETAL AND ADULT OXYHEMOGLOBIN, DE-OXYHEMOGLOBIN, CARBOXYHEMOGLOBIN, AND METHEMOGLOBIN

NARCIS (Netherlands)

ZIJLSTRA, WG; MEEUWSENVANDERROEST, WP

We determined the millimolar absorptivities of the four clinically relevant derivatives of fetal and adult human hemoglobin in the visible and near-infrared spectral range (450-1000 nm). As expected, spectral absorption curves of similar shape were found, but the small differences between fetal and

From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

Science.gov (United States)

Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

2005-05-01

Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

Cortical surface area and cortical thickness in the precuneus of adult humans.

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Bruner, E; Román, F J; de la Cuétara, J M; Martin-Loeches, M; Colom, R

2015-02-12

The precuneus has received considerable attention in the last decade, because of its cognitive functions, its role as a central node of the brain networks, and its involvement in neurodegenerative processes. Paleoneurological studies suggested that form changes in the deep parietal areas represent a major character associated with the origin of the modern human brain morphology. A recent neuroanatomical survey based on shape analysis suggests that the proportions of the precuneus are also a determinant source of overall brain geometrical differences among adult individuals, influencing the brain spatial organization. Here, we evaluate the variation of cortical thickness and cortical surface area of the precuneus in a sample of adult humans, and their relation with geometry and cognition. Precuneal thickness and surface area are not correlated. There is a marked individual variation. The right precuneus is thinner and larger than the left one, but there are relevant fluctuating asymmetries, with only a modest correlation between the hemispheres. Males have a thicker cortex but differences in cortical area are not significant between sexes. The surface area of the precuneus shows a positive allometry with the brain surface area, although the correlation is modest. The dilation/contraction of the precuneus, described as a major factor of variability within adult humans, is associated with absolute increase/decrease of its surface, but not with variation in thickness. Precuneal thickness, precuneal surface area and precuneal morphology are not correlated with psychological factors such as intelligence, working memory, attention control, and processing speed, stressing further possible roles of this area in supporting default mode functions. Beyond gross morphology, the processes underlying the large phenotypic variation of the precuneus must be further investigated through specific cellular analyses, aimed at considering differences in cellular size, density

On the nature and evolution of the neural bases of human language

Science.gov (United States)

Lieberman, Philip

2002-01-01

The traditional theory equating the brain bases of language with Broca's and Wernicke's neocortical areas is wrong. Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, and comprehending the meaning of sentences. When we hear or read a word, neural structures involved in the perception or real-world associations of the word are activated as well as posterior cortical regions adjacent to Wernicke's area. Many areas of the neocortex and subcortical structures support the cortical-striatal-cortical circuits that confer complex syntactic ability, speech production, and a large vocabulary. However, many of these structures also form part of the neural circuits regulating other aspects of behavior. For example, the basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human linguistic ability and abstract reasoning. The cerebellum, traditionally associated with motor control, is active in motor learning. The basal ganglia are also key elements in reward-based learning. Data from studies of Broca's aphasia, Parkinson's disease, hypoxia, focal brain damage, and a genetically transmitted brain anomaly (the putative "language gene," family KE), and from comparative studies of the brains and behavior of other species, demonstrate that the basal ganglia sequence the discrete elements that constitute a complete motor act, syntactic process, or thought process. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. As Dobzansky put it, "Nothing in biology makes sense except in the light of evolution" (cited in Mayr, 1982). That applies with as much force to the human brain and the neural bases of language as it does to the human foot or jaw. The converse follows: the mark of evolution on

A Transcriptomic and Epigenomic Comparison of Fetal and Adult Human Cardiac Fibroblasts Reveals Novel Key Transcription Factors in Adult Cardiac Fibroblasts

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Malin K.B. Jonsson, PhD

2016-12-01

Full Text Available Cardiovascular disease remains the number one global cause of death and presents as multiple phenotypes in which the interplay between cardiomyocytes and cardiac fibroblasts (CFs has become increasingly highlighted. Fetal and adult CFs influence neighboring cardiomyocytes in different ways. Thus far, a detailed comparison between the two is lacking. Using a genome-wide approach, we identified and validated 2 crucial players for maintaining the adult primary human CF phenotype. Knockdown of these factors induced significant phenotypical changes, including senescence and reduced collagen gene expression. These may now represent novel therapeutic targets against deleterious functions of CFs in adult cardiovascular disease.

Neurologic function during developmental and adult stages in Dab1(scm) (scrambler) mutant mice.

Science.gov (United States)

Jacquelin, C; Strazielle, C; Lalonde, R

2012-01-01

Homozygous Dab1(scm) mouse mutants with cell ectopias in cerebellar cortex, hippocampus, and neocortex were compared to non-ataxic controls on the SHIRPA primary screening battery on postnatal days 8, 15, and 22, as well as in the adult period. Dab1(scm) mutants were distinguished from non-ataxic controls as early as postnatal day 8 based on body tremor, gait anomalies, and body weight. On postnatal day 15, motor coordination deficits were evident on horizontal bar and inclined or vertical grid tests in association with a weaker grip strength. Likewise, mutants were distinguished from controls on drop righting and hindpaw clasping tests. Further differences were detected on postnatal day 22 in the form of fewer visual placing, touch escape, trunk curl, freezing, and vocalization responses, as well as squares traversed in the open-field. Evaluation at the adult age demonstrated similar impairments, indicative of permanent motor alterations. Neuronal metabolic activity was estimated by cytochrome oxidase histochemistry on cerebellar sections. Cerebellar cortical layers and efferent deep nuclei of Dab1(scm) mice appeared hypometabolic relative to non-ataxic mice despite normal metabolism in both regular and ectopic Purkinje cells. Copyright © 2011 Elsevier B.V. All rights reserved.

Plasticity of adult human pancreatic duct cells by neurogenin3-mediated reprogramming.

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Nathalie Swales

Full Text Available AIMS/HYPOTHESIS: Duct cells isolated from adult human pancreas can be reprogrammed to express islet beta cell genes by adenoviral transduction of the developmental transcription factor neurogenin3 (Ngn3. In this study we aimed to fully characterize the extent of this reprogramming and intended to improve it. METHODS: The extent of the Ngn3-mediated duct-to-endocrine cell reprogramming was measured employing genome wide mRNA profiling. By modulation of the Delta-Notch signaling or addition of pancreatic endocrine transcription factors Myt1, MafA and Pdx1 we intended to improve the reprogramming. RESULTS: Ngn3 stimulates duct cells to express a focused set of genes that are characteristic for islet endocrine cells and/or neural tissues. This neuro-endocrine shift however, is incomplete with less than 10% of full duct-to-endocrine reprogramming achieved. Transduction of exogenous Ngn3 activates endogenous Ngn3 suggesting auto-activation of this gene. Furthermore, pancreatic endocrine reprogramming of human duct cells can be moderately enhanced by inhibition of Delta-Notch signaling as well as by co-expressing the transcription factor Myt1, but not MafA and Pdx1. CONCLUSIONS/INTERPRETATION: The results provide further insight into the plasticity of adult human duct cells and suggest measurable routes to enhance Ngn3-mediated in vitro reprogramming protocols for regenerative beta cell therapy in diabetes.

Comparison of Kaposi Sarcoma risk in human immunodeficiency virus-positive adults across 5 continents

DEFF Research Database (Denmark)

Rohner, Eliane; Bütikofer, Lukas; Schmidlin, Kurt

2017-01-01

Background: We compared Kaposi sarcoma (KS) risk in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America. Methods: We included cohort data of human immunodeficiency virus (HIV)-positive adults who started ART after 1995 within...... KS risk was 6 times higher in men who have sex with men (aHR, 5.95; 95% CI, 5.09-6.96) than in women. Comparing patients with current CD4 cell counts ≥700 cells/μL with those whose counts were ...% in other regions. Conclusions. Despite important ART-related declines in KS incidence, men and women in South Africa and men who have sex with men remain at increased KS risk, likely due to high human herpesvirus 8 coinfection rates. Early ART initiation and maintenance of high CD4 cell counts...

Immunohistochemical Study of Expression of Sohlh1 and Sohlh2 in Normal Adult Human Tissues.

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Xiaoli Zhang

Full Text Available The expression pattern of Sohlh1 (spermatogenesis and oogenesis specific basic helix-loop-helix 1 and Sohlh2 in mice has been reported in previous studies. Sohlh1 and Sohlh2 are specifically expressed in spermatogonia, prespermatogonia in male mice and oocytes of primordial and primary follicles in female mice. In this report, we studied the expression pattern of Sohlh1 and Sohlh2 in human adult tissues. Immunohistochemical staining of Sohlh1 and Sohlh2 was performed in 5 samples of normal ovaries and testes, respectively. The results revealed that Sohlh genes are not only expressed in oocytes and spermatogonia, but also in granular cells, theca cells, Sertoli cells and Leydig cells, and in smooth muscles of blood vessel walls. To further investigate the expression of Sohlh genes in other adult human tissues, we collected representative normal adult tissues developed from three embryonic germ layers. Compared with the expression in mice, Sohlhs exhibited a much more extensive expression pattern in human tissues. Sohlhs were detected in testis, ovary and epithelia developed from embryonic endoderm, ectoderm and tissues developed from embryonic mesoderm. Sohlh signals were found in spermatogonia, Sertoli cells and also Leydig cells in testis, while in ovary, the expression was mainly in oocytes of primordial and primary follicles, granular cells and theca cells of secondary follicles. Compared with Sohlh2, the expression of Sohlh1 was stronger and more extensive. Our study explored the expression of Sohlh genes in human tissues and might provide insights for functional studies of Sohlh genes.

Estimated Human and Economic Burden of Four Major Adult Vaccine-Preventable Diseases in the United States, 2013

OpenAIRE

McLaughlin, John M.; McGinnis, Justin J.; Tan, Litjen; Mercatante, Annette; Fortuna, Joseph

2015-01-01

Low uptake of routinely recommended adult immunizations is a public health concern. Using data from the peer-reviewed literature, government disease-surveillance programs, and the US Census, we developed a customizable model to estimate human and economic burden caused by four major adult vaccine-preventable diseases (VPD) in 2013 in the United States, and for each US state individually. To estimate the number of cases for each adult VPD for a given population, we multiplied age-specific inci...

Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males

Science.gov (United States)

Mokrysz, C; Freeman, T P; Korkki, S; Griffiths, K; Curran, H V

2016-01-01

Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals. Whether these findings translate to humans has not yet been investigated. Here we believe we conducted the first study to compare the acute effects of cannabis in human adolescent (n=20; 16–17 years old) and adult (n=20; 24–28 years old) male cannabis users, in a placebo-controlled, double-blind cross-over design. After inhaling vaporized active or placebo cannabis, participants completed tasks assessing spatial working memory, episodic memory and response inhibition, alongside measures of blood pressure and heart rate, psychotomimetic symptoms and subjective drug effects (for example, ‘stoned', ‘want to have cannabis'). Results showed that on active cannabis, adolescents felt less stoned and reported fewer psychotomimetic symptoms than adults. Further, adults but not adolescents were more anxious and less alert during the active cannabis session (both pre- and post-drug administration). Following cannabis, cognitive impairment (reaction time on spatial working memory and prose recall following a delay) was greater in adults than adolescents. By contrast, cannabis impaired response inhibition accuracy in adolescents but not in adults. Moreover, following drug administration, the adolescents did not show satiety; instead they wanted more cannabis regardless of whether they had taken active or placebo cannabis, while the opposite was seen for adults. These contrasting profiles of adolescent resilience (blunted subjective, memory, physiological and psychotomimetic effects) and vulnerability (lack of satiety, impaired inhibitory processes) show some degree of translation from preclinical findings, and may contribute to escalated cannabis use by human adolescents. PMID:27898071

Nogo-A is a reliable oligodendroglial marker in adult human and mouse CNS and in demyelinated lesions

DEFF Research Database (Denmark)

Kuhlmann, Tanja; Remington, Leah; Maruschak, Brigitte

2007-01-01

to be strongly expressed in mature oligodendrocytes in vivo. In the present investigation we analyzed the expression patterns of Nogo-A in adult mouse and human CNS as well as in demyelinating animal models and multiple sclerosis lesions. Nogo-A expression was compared with that of other frequently used...... oligodendroglial markers such as CC1, CNP, and in situ hybridization for proteolipid protein mRNA. Nogo-A strongly and reliably labeled oligodendrocytes in the adult CNS as well as in demyelinating lesions and thus represents a valuable tool for the identification of oligodendrocytes in human and mouse CNS tissue...

Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults

DEFF Research Database (Denmark)

Ewen, Katherine A; Olesen, Inge A; Winge, Sofia B

2013-01-01

development and to ascertain whether FGFR3 signalling is linked to germ cell proliferation and the pathogenesis of testicular germ cell tumours (TGCTs) of young adult men. Using RT-PCR, immunohistochemistry and Western blotting, we examined 58 specimens of human testes throughout development for FGFR3...... expression, and then compared expression of FGFR3 with proliferation markers (PCNA or Ki67). We also analysed for FGFR3 expression 30 TGCTs and 28 testes containing the tumour precursor cell, carcinoma in situ (CIS). Fetal and adult testes expressed exclusively the FGFR3IIIc isoform. FGFR3 protein expression...... was restricted to the cytoplasm/plasma membrane of spermatogonia and was most prevalent at mid-gestation, infancy and from puberty onwards. Phosphorylated (p)FGFR was detected in pre-spermatogonia at mid-gestation and in spermatogonia during puberty and in the adult testis. Throughout normal human testis...

40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before April 7, 2006. 26.1704 Section 26.1704 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS...

40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after April 7, 2006. 26.1705 Section 26.1705 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS...

Dynamic of distribution of human bone marrow-derived mesenchymal stem cells after transplantation into adult unconditioned mice.

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Allers, Carolina; Sierralta, Walter D; Neubauer, Sonia; Rivera, Francisco; Minguell, José J; Conget, Paulette A

2004-08-27

The use of mesenchymal stem cells (MSC) for cell therapy relies on their capacity to engraft and survive long-term in the appropriate target tissue(s). Animal models have demonstrated that the syngeneic or xenogeneic transplantation of MSC results in donor engraftment into the bone marrow and other tissues of conditioned recipients. However, there are no reliable data showing the fate of human MSC infused into conditioned or unconditioned adult recipients. In the present study, the authors investigated, by using imaging, polymerase chain reaction (PCR), and in situ hybridization, the biodistribution of human bone marrow-derived MSC after intravenous infusion into unconditioned adult nude mice. As assessed by imaging (gamma camera), PCR, and in situ hybridization analysis, the authors' results demonstrate the presence of human MSC in bone marrow, spleen, and mesenchymal tissues of recipient mice. These results suggest that human MSC transplantation into unconditioned recipients represents an option for providing cellular therapy and avoids the complications associated with drugs or radiation conditioning.

Thyroid hormone regulates the expression of the sonic hedgehog signaling pathway in the embryonic and adult Mammalian brain.

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Desouza, Lynette A; Sathanoori, Malini; Kapoor, Richa; Rajadhyaksha, Neha; Gonzalez, Luis E; Kottmann, Andreas H; Tole, Shubha; Vaidya, Vidita A

2011-05-01

Thyroid hormone is important for development and plasticity in the immature and adult mammalian brain. Several thyroid hormone-responsive genes are regulated during specific developmental time windows, with relatively few influenced across the lifespan. We provide novel evidence that thyroid hormone regulates expression of the key developmental morphogen sonic hedgehog (Shh), and its coreceptors patched (Ptc) and smoothened (Smo), in the early embryonic and adult forebrain. Maternal hypo- and hyperthyroidism bidirectionally influenced Shh mRNA in embryonic forebrain signaling centers at stages before fetal thyroid hormone synthesis. Further, Smo and Ptc expression were significantly decreased in the forebrain of embryos derived from hypothyroid dams. Adult-onset thyroid hormone perturbations also regulated expression of the Shh pathway bidirectionally, with a significant induction of Shh, Ptc, and Smo after hyperthyroidism and a decline in Smo expression in the hypothyroid brain. Short-term T₃ administration resulted in a significant induction of cortical Shh mRNA expression and also enhanced reporter gene expression in Shh(+/LacZ) mice. Further, acute T₃ treatment of cortical neuronal cultures resulted in a rapid and significant increase in Shh mRNA, suggesting direct effects. Chromatin immunoprecipitation assays performed on adult neocortex indicated enhanced histone acetylation at the Shh promoter after acute T₃ administration, providing further support that Shh is a thyroid hormone-responsive gene. Our results indicate that maternal and adult-onset perturbations of euthyroid status cause robust and region-specific changes in the Shh pathway in the embryonic and adult forebrain, implicating Shh as a possible mechanistic link for specific neurodevelopmental effects of thyroid hormone.

Perspectives on Adult Education, Human Resource Development, and the Emergence of Workforce Development

Science.gov (United States)

Jacobs, Ronald L.

2014-01-01

This article presents a perspective on the relationship between adult education and human resource development of the past two decades and the subsequent emergence of workforce development. The lesson taken from the article should be more than simply a recounting of events related to these fields of study. Instead, the more general lesson may be…

In-Depth Analysis of Human Neonatal and Adult IgM Antibody Repertoires

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Binbin Hong

2018-02-01

Full Text Available Although high-throughput sequencing and associated bioinformatics technologies have enabled the in-depth, sequence-based characterization of human immune repertoires, only a few studies on a relatively small number of sequences explored the characteristics of antibody repertoires in neonates, with contradictory conclusions. To gain a more comprehensive understanding of the human IgM antibody repertoire, we performed Illumina sequencing and IMGT/HighV-QUEST analysis of IgM heavy chain repertoire of the B lymphocytes from the cord blood (CB of neonates, as well as the repertoire from peripheral blood of healthy human adults (HH. The comparative study revealed unexpectedly high levels of similarity between the neonatal and adult repertoires. In both repertoires, the VDJ gene usage showed no significant difference, and the most frequently used VDJ gene was IGHV4-59, IGHD3-10, and IGHJ3. The average amino acid (aa length of CDR1 (CB: 8.5, HH: 8.4 and CDR2 (CB: 7.6, HH: 7.5, as well as the aa composition and the average hydrophobicity of the CDR3 demonstrated no significant difference between the two repertories. However, the average aa length of CDR3 was longer in the HH repertoire than the CB repertoire (CB: 14.5, HH: 15.5. Besides, the frequencies of aa mutations in CDR1 (CB: 19.33%, HH: 25.84% and CDR2 (CB: 9.26%, HH: 17.82% were higher in the HH repertoire compared to the CB repertoire. Interestingly, the most prominent difference between the two repertoires was the occurrence of N2 addition (CB: 64.87%, HH: 85.69%, a process that occurs during V-D-J recombination for introducing random nucleotide additions between D- and J-gene segments. The antibody repertoire of healthy adults was more diverse than that of neonates largely due to the higher occurrence of N2 addition. These findings may lead to a better understanding of antibody development and evolution pathways and may have potential practical value for facilitating the generation of more

Neocortical Development in Brain of Young Children

DEFF Research Database (Denmark)

Kjaer, Majken; Fabricius, Katrine; Sigaard, Rasmus Krarup

2017-01-01

The early postnatal development of neuron and glia numbers is poorly documented in human brain. Therefore we estimated using design-based stereological methods the regional volumes of neocortex and the numbers of neocortical neurons and glial cells for 10 children (4 girls and 6 boys), ranging from...... neonate to 3 years of age. The 10 infants had a mean of 20.7 × 109 neocortical neurons (range 18.0-24.8 × 109) estimated with a coefficient of variation (CV) = 0.11; this range is similar to adult neuron numbers. The glia populations were 10.5 × 109 oligodendrocytes (range 5.0-16.0 × 109; CV = 0.40); 5...

Low/Negative Expression of PDGFR-α Identifies the Candidate Primary Mesenchymal Stromal Cells in Adult Human Bone Marrow

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Hongzhe Li

2014-12-01

Full Text Available Human bone marrow (BM contains a rare population of nonhematopoietic mesenchymal stromal cells (MSCs, which are of central importance for the hematopoietic microenvironment. However, the precise phenotypic definition of these cells in adult BM has not yet been reported. In this study, we show that low/negative expression of CD140a (PDGFR-α on lin−/CD45−/CD271+ BM cells identified a cell population with very high MSC activity, measured as fibroblastic colony-forming unit frequency and typical in vitro and in vivo stroma formation and differentiation capacities. Furthermore, these cells exhibited high levels of genes associated with mesenchymal lineages and HSC supportive function. Moreover, lin−/CD45−/CD271+/CD140alow/− cells effectively mediated the ex vivo expansion of transplantable CD34+ hematopoietic stem cells. Taken together, these data indicate that CD140a is a key negative selection marker for adult human BM-MSCs, which enables to prospectively isolate a close to pure population of candidate human adult stroma stem/progenitor cells with potent hematopoiesis-supporting capacity.

Adult, embryonic and fetal hemoglobin are expressed in human glioblastoma cells.

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Emara, Marwan; Turner, A Robert; Allalunis-Turner, Joan

2014-02-01

Hemoglobin is a hemoprotein, produced mainly in erythrocytes circulating in the blood. However, non-erythroid hemoglobins have been previously reported in other cell types including human and rodent neurons of embryonic and adult brain, but not astrocytes and oligodendrocytes. Human glioblastoma multiforme (GBM) is the most aggressive tumor among gliomas. However, despite extensive basic and clinical research studies on GBM cells, little is known about glial defence mechanisms that allow these cells to survive and resist various types of treatment. We have shown previously that the newest members of vertebrate globin family, neuroglobin (Ngb) and cytoglobin (Cygb), are expressed in human GBM cells. In this study, we sought to determine whether hemoglobin is also expressed in GBM cells. Conventional RT-PCR, DNA sequencing, western blot analysis, mass spectrometry and fluorescence microscopy were used to investigate globin expression in GBM cell lines (M006x, M059J, M059K, M010b, U87R and U87T) that have unique characteristics in terms of tumor invasion and response to radiotherapy and hypoxia. The data showed that α, β, γ, δ, ζ and ε globins are expressed in all tested GBM cell lines. To our knowledge, we are the first to report expression of fetal, embryonic and adult hemoglobin in GBM cells under normal physiological conditions that may suggest an undefined function of those expressed hemoglobins. Together with our previous reports on globins (Ngb and Cygb) expression in GBM cells, the expression of different hemoglobins may constitute a part of series of active defence mechanisms supporting these cells to resist various types of treatments including chemotherapy and radiotherapy.

Exocytosis of ATP From Astrocytes Modulates Phasic and Tonic Inhibition in the Neocortex

Science.gov (United States)

Rasooli-Nejad, Seyed; Andrew, Jemma; Haydon, Philip G.; Pankratov, Yuriy

2014-01-01

in the neocortex. PMID:24409095

Exocytosis of ATP from astrocytes modulates phasic and tonic inhibition in the neocortex.

Directory of Open Access Journals (Sweden)

Ulyana Lalo

2014-01-01

ATP from astrocytes in the neocortex.

Functional histology of the macula flava in the human vocal fold--Part 1: its role in the adult vocal fold.

Science.gov (United States)

Sato, Kiminori; Umeno, Hirohito; Nakashima, Tadashi

2010-01-01

This study aims to clarify the role of the maculae flavae (MFe) in the human adult vocal fold mucosa (VFM). Our current results concerning MFe in the human adult VFM are summarized. MFe were found to be composed of dense masses of vocal fold stellate cells (VFSCs) and extracellular matrices (EM), such as fibrous proteins and glycosaminoglycans, which are essential for the EM in the human VFM. VFSCs in the MFe demonstrated marked morphologic differences from conventional fibroblasts. They were irregular and stellate in shape and possessed slender cytoplasmic processes. They had well-developed intracellular organelles. A number of vesicles were present at the periphery of the cytoplasm. They constantly synthesized EM. The VFSCs possessed lipid droplets and stored vitamin A. VFSCs formed an independent cell category of cells in the human VFM. The VFSCs in aged adult MFe decreased their activity, and had abnormal metabolism. Human MFe including VFSCs seem to be involved in the metabolism of EM which are essential for the viscoelasticity of the lamina propria of the VFM, and to be responsible for maintaining the characteristic layered structure of the human VFM. Age-related changes in VFSCs were found to influence the metabolism of EM in the VFM. (c) 2010 S. Karger AG, Basel.

Equality and Human Capital: Conflicting Concepts within State-Funded Adult Education in Ireland

Science.gov (United States)

Hurley, Kevin

2015-01-01

This article offers a critique of the concept of equality as it informs the White Paper on Adult Education: Learning for Life (2000). It also outlines the extent to which human capital theory can be seen to have effectively colonised lifelong learning from the outset of its adoption by the European Union with highly constraining implications for…

Neurobiology of Intimate Relationships

OpenAIRE

Ozge Saracli; Nuray Atasoy; Elif Karaahmet

2012-01-01

The limbic brain appears to be the source of basic emotions and urges. In contrast the neocortex gives humans the ability to think in abstract and symbolic terms and to use language. Emotions by neural projections from the limbic system to neocortex influence all aspect of cognition, from perception to rational decision making. Although the cases whose intellectual and motor abilities appeared fully functional, decision making ability and emotional processing impaired together after a damage ...

Yakın İlişkilerin Nörobiyolojisi

OpenAIRE

Saraçlı, Özge; Atasoy, Nuray; Karaahmet, Elif

2014-01-01

The limbic brain appears to be the source of basic emotions and urges. In contrast the neocortex gives humans the ability to think in abstract and symbolic terms and to use language. Emotions by neural projections from the limbic system to neocortex influence all aspect of cognition, from perception to rational decision making. Although the cases whose intellectual and motor abilities appeared fully functional, decision making ability and emotional processing impaired together after a damage ...

Identification of distinct layers within the stratified squamous epithelium of the adult human true vocal fold.

Science.gov (United States)

Dowdall, Jayme R; Sadow, Peter M; Hartnick, Christopher; Vinarsky, Vladimir; Mou, Hongmei; Zhao, Rui; Song, Phillip C; Franco, Ramon A; Rajagopal, Jayaraj

2015-09-01

A precise molecular schema for classifying the different cell types of the normal human vocal fold epithelium is lacking. We hypothesize that the true vocal fold epithelium has a cellular architecture and organization similar to that of other stratified squamous epithelia including the skin, cornea, oral mucosa, and esophagus. In analogy to disorders of the skin and gastrointestinal tract, a molecular definition of the normal cell types within the human vocal fold epithelium and a description of their geometric relationships should serve as a foundation for characterizing cellular changes associated with metaplasia, dysplasia, and cancer. Qualitative study with adult human larynges. Histologic sections of normal human laryngeal tissue were analyzed for morphology (hematoxylin and eosin) and immunohistochemical protein expression profile, including cytokeratins (CK13 and CK14), cornified envelope proteins (involucrin), basal cells (NGFR/p75), and proliferation markers (Ki67). We demonstrated that three distinct cell strata with unique marker profiles are present within the stratified squamous epithelium of the true vocal fold. We used these definitions to establish that cell proliferation is restricted to certain cell types and layers within the epithelium. These distinct cell types are reproducible across five normal adult larynges. We have established that three layers of cells are present within the normal adult stratified squamous epithelium of the true vocal fold. Furthermore, replicating cell populations are largely restricted to the parabasal strata within the epithelium. This delineation of distinct cell populations will facilitate future studies of vocal fold regeneration and cancer. N/A. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Sensitive Tumorigenic Potential Evaluation of Adult Human Multipotent Neural Cells Immortalized by hTERT Gene Transduction.

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Kee Hang Lee

Full Text Available Stem cells and therapeutic genes are emerging as a new therapeutic approach to treat various neurodegenerative diseases with few effective treatment options. However, potential formation of tumors by stem cells has hampered their clinical application. Moreover, adequate preclinical platforms to precisely test tumorigenic potential of stem cells are controversial. In this study, we compared the sensitivity of various animal models for in vivo stem cell tumorigenicity testing to identify the most sensitive platform. Then, tumorigenic potential of adult human multipotent neural cells (ahMNCs immortalized by the human telomerase reverse transcriptase (hTERT gene was examined as a stem cell model with therapeutic genes. When human glioblastoma (GBM cells were injected into adult (4-6-week-old Balb/c-nu, adult NOD/SCID, adult NOG, or neonate (1-2-week-old NOG mice, the neonate NOG mice showed significantly faster tumorigenesis than that of the other groups regardless of intracranial or subcutaneous injection route. Two kinds of ahMNCs (682TL and 779TL were primary cultured from surgical samples of patients with temporal lobe epilepsy. Although the ahMNCs were immortalized by lentiviral hTERT gene delivery (hTERT-682TL and hTERT-779TL, they did not form any detectable masses, even in the most sensitive neonate NOG mouse platform. Moreover, the hTERT-ahMNCs had no gross chromosomal abnormalities on a karyotype analysis. Taken together, our data suggest that neonate NOG mice could be a sensitive animal platform to test tumorigenic potential of stem cell therapeutics and that ahMNCs could be a genetically stable stem cell source with little tumorigenic activity to develop regenerative treatments for neurodegenerative diseases.

Network-level structure-function relationships in human neocortex

NARCIS (Netherlands)

Miŝic, Bratislav; Betzel, Richard F.; De Reus, Marcel A.; Van Den Heuvel, Martijn P.; Berman, Marc G.; McIntosh, Anthony R.; Sporns, Olaf

2016-01-01

The dynamics of spontaneous fluctuations in neural activity are shaped by underlying patterns of anatomical connectivity. While numerous studies have demonstrated edge-wise correspondence between structural and functional connections, much less is known about how large-scale coherent functional

A new myeloarchitectonic map of the human neocortex based on data from the Vogt-Vogt school

NARCIS (Netherlands)

Nieuwenhuys, R.; Broere, Cees A J; Cerliani, L.

The human cerebral cortex contains numerous myelinated fibres, the arrangement and density of which is by no means homogeneous throughout the cortex. Local differences in the spatial organization of these fibres render it possible to recognize areas with a different myeloarchitecture. The

A Theory of How Columns in the Neocortex Enable Learning the Structure of the World

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Jeff Hawkins

2017-10-01

Full Text Available Neocortical regions are organized into columns and layers. Connections between layers run mostly perpendicular to the surface suggesting a columnar functional organization. Some layers have long-range excitatory lateral connections suggesting interactions between columns. Similar patterns of connectivity exist in all regions but their exact role remain a mystery. In this paper, we propose a network model composed of columns and layers that performs robust object learning and recognition. Each column integrates its changing input over time to learn complete predictive models of observed objects. Excitatory lateral connections across columns allow the network to more rapidly infer objects based on the partial knowledge of adjacent columns. Because columns integrate input over time and space, the network learns models of complex objects that extend well beyond the receptive field of individual cells. Our network model introduces a new feature to cortical columns. We propose that a representation of location relative to the object being sensed is calculated within the sub-granular layers of each column. The location signal is provided as an input to the network, where it is combined with sensory data. Our model contains two layers and one or more columns. Simulations show that using Hebbian-like learning rules small single-column networks can learn to recognize hundreds of objects, with each object containing tens of features. Multi-column networks recognize objects with significantly fewer movements of the sensory receptors. Given the ubiquity of columnar and laminar connectivity patterns throughout the neocortex, we propose that columns and regions have more powerful recognition and modeling capabilities than previously assumed.

Is the social brain theory applicable to human individual differences? Relationship between sociability personality dimension and brain size.

Science.gov (United States)

Horváth, Klára; Martos, János; Mihalik, Béla; Bódizs, Róbert

2011-06-17

Our study intends to examine whether the social brain theory is applicable to human individual differences. According to the social brain theory primates have larger brains as it could be expected from their body sizes due to the adaptation to a more complex social life. Regarding humans there were few studies about the relationship between theory of mind and frontal and temporal brain lobes. We hypothesized that these brain lobes, as well as the whole cerebrum and neocortex are in connection with the Sociability personality dimension that is associated with individuals' social lives. Our findings support this hypothesis as Sociability correlated positively with the examined brain structures if we control the effects of body size differences and age. These results suggest that the social brain theory can be extended to human interindividual differences and they have some implications to personality psychology too.

Regulated gene expression in cultured type II cells of adult human lung

OpenAIRE

Ballard, Philip L.; Lee, Jae W.; Fang, Xiaohui; Chapin, Cheryl; Allen, Lennell; Segal, Mark R.; Fischer, Horst; Illek, Beate; Gonzales, Linda W.; Kolla, Venkatadri; Matthay, Michael A.

2010-01-01

Alveolar type II cells have multiple functions, including surfactant production and fluid clearance, which are critical for lung function. Differentiation of type II cells occurs in cultured fetal lung epithelial cells treated with dexamethasone plus cAMP and isobutylmethylxanthine (DCI) and involves increased expression of 388 genes. In this study, type II cells of human adult lung were isolated at ∼95% purity, and gene expression was determined (Affymetrix) before and after culturing 5 days...

The language of geometry: Fast comprehension of geometrical primitives and rules in human adults and preschoolers

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Amalric, Marie; Wang, Liping; Figueira, Santiago; Sigman, Mariano; Dehaene, Stanislas

2017-01-01

During language processing, humans form complex embedded representations from sequential inputs. Here, we ask whether a “geometrical language” with recursive embedding also underlies the human ability to encode sequences of spatial locations. We introduce a novel paradigm in which subjects are exposed to a sequence of spatial locations on an octagon, and are asked to predict future locations. The sequences vary in complexity according to a well-defined language comprising elementary primitives and recursive rules. A detailed analysis of error patterns indicates that primitives of symmetry and rotation are spontaneously detected and used by adults, preschoolers, and adult members of an indigene group in the Amazon, the Munduruku, who have a restricted numerical and geometrical lexicon and limited access to schooling. Furthermore, subjects readily combine these geometrical primitives into hierarchically organized expressions. By evaluating a large set of such combinations, we obtained a first view of the language needed to account for the representation of visuospatial sequences in humans, and conclude that they encode visuospatial sequences by minimizing the complexity of the structured expressions that capture them. PMID:28125595

Characterization of Insulin-Immunoreactive Cells and Endocrine Cells Within the Duct System of the Adult Human Pancreas.

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Li, Rong; Zhang, Xiaoxi; Yu, Lan; Zou, Xia; Zhao, Hailu

2016-01-01

The adult pancreatic duct system accommodates endocrine cells that have the potential to produce insulin. Here we report the characterization and distribution of insulin-immunoreactive cells and endocrine cells within the ductal units of adult human pancreas. Sequential pancreas sections from 12 nondiabetic adults were stained with biomarkers of ductal epithelial cells (cytokeratin 19), acinar cells (amylase), endocrine cells (chromogranin A; neuron-specific enolase), islet hormones (insulin, glucagon, somatostatin, pancreatic polypeptide), cell proliferation (Ki-67), and neogenesis (CD29). The number of islet hormone-immunoreactive cells increased from large ducts to the terminal branches. The insulin-producing cells outnumbered endocrine cells reactive for glucagon, somatostatin, or pancreatic polypeptide. The proportions of insulin-immunoreactive count compared with local islets (100% as a baseline) were 1.5% for the main ducts, 7.2% for interlobular ducts, 24.8% for intralobular ducts, 67.9% for intercalated ducts, and 348.9% for centroacinar cells. Both Ki-67- and CD29-labeled cells were predominantly localized in the terminal branches around the islets. The terminal branches also showed cells coexpressing islet hormones and cytokeratin 19. The adult human pancreatic ducts showed islet hormone-producing cells. The insulin-reactive cells predominantly localized in terminal branches where they may retain potential capability for β-cell neogenesis.

The effect of human engagement depicted in contextual photographs on the visual attention patterns of adults with traumatic brain injury.

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Thiessen, Amber; Brown, Jessica; Beukelman, David; Hux, Karen

2017-09-01

Photographs are a frequently employed tool for the rehabilitation of adults with traumatic brain injury (TBI). Speech-language pathologists (SLPs) working with these individuals must select photos that are easily identifiable and meaningful to their clients. In this investigation, we examined the visual attention response to camera- (i.e., depicted human figure looking toward camera) and task-engaged (i.e., depicted human figure looking at and touching an object) contextual photographs for a group of adults with TBI and a group of adults without neurological conditions. Eye-tracking technology served to accurately and objectively measure visual fixations. Although differences were hypothesized given the cognitive deficits associated with TBI, study results revealed little difference in the visual fixation patterns of adults with and without TBI. Specifically, both groups of participants tended to fixate rapidly on the depicted human figure and fixate more on objects in which a human figure was task-engaged than when a human figure was camera-engaged. These results indicate that strategic placement of human figures in a contextual photograph may modify the way in which individuals with TBI visually attend to and interpret photographs. In addition, task-engagement appears to have a guiding effect on visual attention that may be of benefit to SLPs hoping to select more effective contextual photographs for their clients with TBI. Finally, the limited differences in visual attention patterns between individuals with TBI and their age and gender matched peers without neurological impairments indicates that these two groups find similar photograph regions to be worthy of visual fixation. Readers will gain knowledge regarding the photograph selection process for individuals with TBI. In addition, readers will be able to identify camera- and task-engaged photographs and to explain why task-engagement may be a beneficial component of contextual photographs. Copyright © 2017

Evidence for a stem cell hierarchy in the adult human breast

DEFF Research Database (Denmark)

Villadsen, René; Fridriksdottir, Agla J; Rønnov-Jessen, Lone

2007-01-01

Cellular pathways that contribute to adult human mammary gland architecture and lineages have not been previously described. In this study, we identify a candidate stem cell niche in ducts and zones containing progenitor cells in lobules. Putative stem cells residing in ducts were essentially...... in laminin-rich extracellular matrix gels. Staining for the lineage markers keratins K14 and K19 further revealed multipotent cells in the stem cell zone and three lineage-restricted cell types outside this zone. Multiparameter cell sorting and functional characterization with reference to anatomical sites...

5' Rapid Amplification of cDNA Ends and Illumina MiSeq Reveals B Cell Receptor Features in Healthy Adults, Adults With Chronic HIV-1 Infection, Cord Blood, and Humanized Mice.

Science.gov (United States)

Waltari, Eric; Jia, Manxue; Jiang, Caroline S; Lu, Hong; Huang, Jing; Fernandez, Cristina; Finzi, Andrés; Kaufmann, Daniel E; Markowitz, Martin; Tsuji, Moriya; Wu, Xueling

2018-01-01

Using 5' rapid amplification of cDNA ends, Illumina MiSeq, and basic flow cytometry, we systematically analyzed the expressed B cell receptor (BCR) repertoire in 14 healthy adult PBMCs, 5 HIV-1+ adult PBMCs, 5 cord blood samples, and 3 HIS-CD4/B mice, examining the full-length variable region of μ, γ, α, κ, and λ chains for V-gene usage, somatic hypermutation (SHM), and CDR3 length. Adding to the known repertoire of healthy adults, Illumina MiSeq consistently detected small fractions of reads with high mutation frequencies including hypermutated μ reads, and reads with long CDR3s. Additionally, the less studied IgA repertoire displayed similar characteristics to that of IgG. Compared to healthy adults, the five HIV-1 chronically infected adults displayed elevated mutation frequencies for all μ, γ, α, κ, and λ chains examined and slightly longer CDR3 lengths for γ, α, and λ. To evaluate the reconstituted human BCR sequences in a humanized mouse model, we analyzed cord blood and HIS-CD4/B mice, which all lacked the typical SHM seen in the adult reference. Furthermore, MiSeq revealed identical unmutated IgM sequences derived from separate cell aliquots, thus for the first time demonstrating rare clonal members of unmutated IgM B cells by sequencing.

Early-life experiences and the development of adult diseases with a focus on mental illness: The Human Birth Theory.

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Maccari, Stefania; Polese, Daniela; Reynaert, Marie-Line; Amici, Tiziana; Morley-Fletcher, Sara; Fagioli, Francesca

2017-02-07

In mammals, early adverse experiences, including mother-pup interactions, shape the response of an individual to chronic stress or to stress-related diseases during adult life. This has led to the elaboration of the theory of the developmental origins of health and disease, in particular adult diseases such as cardiovascular and metabolic disorders. In addition, in humans, as stated by Massimo Fagioli's Human Birth Theory, birth is healthy and equal for all individuals, so that mental illness develop exclusively in the postnatal period because of the quality of the relationship in the first year of life. Thus, this review focuses on the importance of programming during the early developmental period on the manifestation of adult diseases in both animal models and humans. Considering the obvious differences between animals and humans we cannot systematically move from animal models to humans. Consequently, in the first part of this review, we will discuss how animal models can be used to dissect the influence of adverse events occurring during the prenatal and postnatal periods on the developmental trajectories of the offspring, and in the second part, we will discuss the role of postnatal critical periods on the development of mental diseases in humans. Epigenetic mechanisms that cause reversible modifications in gene expression, driving the development of a pathological phenotype in response to a negative early postnatal environment, may lie at the core of this programming, thereby providing potential new therapeutic targets. The concept of the Human Birth Theory leads to a comprehension of the mental illness as a pathology of the human relationship immediately after birth and during the first year of life. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Reassembly of adult human testicular cells: can testis cord-like structures be created in vitro?

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Mincheva, M; Sandhowe-Klaverkamp, R; Wistuba, J; Redmann, K; Stukenborg, J-B; Kliesch, S; Schlatt, S

2018-02-01

Can enzymatically dispersed testicular cells from adult men reassemble into seminiferous cord-like structures in vitro? Adult human testicular somatic cells reassembled into testicular cord-like structures via dynamic interactions of Sertoli and peritubular cells. In vitro approaches using dispersed single cell suspensions of human testes to generate seminiferous tubule structures and to initiate their functionality have as yet shown only limited success. Testes from 15 adult gender dysphoria patients (mean ± standard deviation age 35 ± 9.3 years) showing spermatogonial arrest became available for this study after sex-reassignment surgery. In vitro primary testicular somatic cell cultures were generated to explore the self-organizing ability of testicular somatic cells to form testis cords over a 2-week period. Morphological phenotype, protein marker expression and temporal dynamics of cell reassembly were analyzed. Cell suspensions obtained by two-step enzymatic digestion were plated onto glass coverslips in 24-well plates. To obtain adherent somatic cells, the supernatant was discarded on Day 2. The culture of the attached cell population was continued. Reassembly into cord-like structures was analyzed daily by microscopic observations. Endpoints were qualitative changes in morphology. Cell types were characterized by phase-contrast microscopy and immunohistochemistry. Dynamics of cord formation were recorded by time-lapse microscopy. Primary adult human testicular cells underwent sequential morphological changes including compaction and reaggregation resulting in round or elongated cord-like structures. Time-lapse video recordings within the first 4 days of culture revealed highly dynamic processes of migration and coalescence of reaggregated cells. The cellular movements were mediated by peritubular cells. Immunohistochemical analysis showed that both SRY-related high mobility box 9-positive Sertoli and α-smooth muscle actin-positive peritubular myoid cells

The adaptive nature of the human neurocognitive architecture: an alternative model.

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La Cerra, P; Bingham, R

1998-09-15

The model of the human neurocognitive architecture proposed by evolutionary psychologists is based on the presumption that the demands of hunter-gatherer life generated a vast array of cognitive adaptations. Here we present an alternative model. We argue that the problems inherent in the biological markets of ancestral hominids and their mammalian predecessors would have required an adaptively flexible, on-line information-processing system, and would have driven the evolution of a functionally plastic neural substrate, the neocortex, rather than a confederation of evolutionarily prespecified social cognitive adaptations. In alignment with recent neuroscientific evidence, we suggest that human cognitive processes result from the activation of constructed cortical representational networks, which reflect probabilistic relationships between sensory inputs, behavioral responses, and adaptive outcomes. The developmental construction and experiential modification of these networks are mediated by subcortical circuitries that are responsive to the life history regulatory system. As a consequence, these networks are intrinsically adaptively constrained. The theoretical and research implications of this alternative evolutionary model are discussed.

Human Dental Pulp Cells Differentiate toward Neuronal Cells and Promote Neuroregeneration in Adult Organotypic Hippocampal Slices In Vitro.

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Xiao, Li; Ide, Ryoji; Saiki, Chikako; Kumazawa, Yasuo; Okamura, Hisashi

2017-08-11

The adult mammalian central nerve system has fundamental difficulties regarding effective neuroregeneration. The aim of this study is to investigate whether human dental pulp cells (DPCs) can promote neuroregeneration by (i) being differentiated toward neuronal cells and/or (ii) stimulating local neurogenesis in the adult hippocampus. Using immunostaining, we demonstrated that adult human dental pulp contains multipotent DPCs, including STRO-1, CD146 and P75-positive stem cells. DPC-formed spheroids were able to differentiate into neuronal, vascular, osteogenic and cartilaginous lineages under osteogenic induction. However, under neuronal inductive conditions, cells in the DPC-formed spheroids differentiated toward neuronal rather than other lineages. Electrophysiological study showed that these cells consistently exhibit the capacity to produce action potentials, suggesting that they have a functional feature in neuronal cells. We further co-cultivated DPCs with adult mouse hippocampal slices on matrigel in vitro. Immunostaining and presto blue assay showed that DPCs were able to stimulate the growth of neuronal cells (especially neurons) in both the CA1 zone and the edges of the hippocampal slices. Brain-derived neurotrophic factor (BDNF), was expressed in co-cultivated DPCs. In conclusion, our data demonstrated that DPCs are well-suited to differentiate into the neuronal lineage. They are able to stimulate neurogenesis in the adult mouse hippocampus through neurotrophic support in vitro.

Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain.

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Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

2013-01-01

An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain.

Activation of classical brown adipocytes in the adult human perirenal depot is highly correlated with PRDM16-EHMT1 complex expression.

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Gaku Nagano

Full Text Available Brown fat generates heat to protect against cold and obesity. Adrenergic stimulation activates the thermogenic program of brown adipocytes. Although the bioactivity of brown adipose tissue in adult humans had been assumed to very low, several studies using positron emission tomography-computed tomography (PET-CT have detected bioactive brown adipose tissue in adult humans under cold exposure. In this study, we collected adipose tissues obtained from the perirenal regions of adult patients with pheochromocytoma (PHEO or non-functioning adrenal tumors (NF. We demonstrated that perirenal brown adipocytes were activated in adult patients with PHEO. These cells had the molecular characteristics of classical brown fat rather than those of beige/brite fat. Expression of brown adipose tissue markers such as uncoupling protein 1 (UCP1 and cell death-inducing DFFA-like effector A (CIDEA was highly correlated with the amounts of PRD1-BF-1-RIZ1 homologous domain-containing protein-16 (PRDM16 - euchromatic histone-lysine N-methyltransferase 1 (EHMT1 complex, the key transcriptional switch for brown fat development. These results provide novel insights into the reconstruction of human brown adipocytes and their therapeutic application against obesity and its complications such as type 2 diabetes.

Efficient delivery of Cre-recombinase to neurons in vivo and stable transduction of neurons using adeno-associated and lentiviral vectors

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Sablitzky Fred

2004-01-01

Full Text Available Abstract Background Inactivating genes in vivo is an important technique for establishing their function in the adult nervous system. Unfortunately, conventional knockout mice may suffer from several limitations including embryonic or perinatal lethality and the compensatory regulation of other genes. One approach to producing conditional activation or inactivation of genes involves the use of Cre recombinase to remove loxP-flanked segments of DNA. We have studied the effects of delivering Cre to the hippocampus and neocortex of adult mice by injecting replication-deficient adeno-associated virus (AAV and lentiviral (LV vectors into discrete regions of the forebrain. Results Recombinant AAV-Cre, AAV-GFP (green fluorescent protein and LV-Cre-EGFP (enhanced GFP were made with the transgene controlled by the cytomegalovirus promoter. Infecting 293T cells in vitro with AAV-Cre and LV-Cre-EGFP resulted in transduction of most cells as shown by GFP fluorescence and Cre immunoreactivity. Injections of submicrolitre quantities of LV-Cre-EGFP and mixtures of AAV-Cre with AAV-GFP into the neocortex and hippocampus of adult Rosa26 reporter mice resulted in strong Cre and GFP expression in the dentate gyrus and moderate to strong labelling in specific regions of the hippocampus and in the neocortex, mainly in neurons. The pattern of expression of Cre and GFP obtained with AAV and LV vectors was very similar. X-gal staining showed that Cre-mediated recombination had occurred in neurons in the same regions of the brain, starting at 3 days post-injection. No obvious toxic effects of Cre expression were detected even after four weeks post-injection. Conclusion AAV and LV vectors are capable of delivering Cre to neurons in discrete regions of the adult mouse brain and producing recombination.

Limits on efficient human mindreading: convergence across Chinese adults and Semai children.

Science.gov (United States)

Wang, Bo; Hadi, Nur Shafiqah Abdul; Low, Jason

2015-11-01

We tested Apperly and Butterfill's (2009, Psychological Review, 116, 753) theory that humans have two mindreading systems whereby the efficient-system guiding anticipatory glances displays signature limits that do not apply to the flexible system guiding verbal predictions. Experiments 1 and 2 tested urban Mainland-Chinese adults (n = 64) and Experiment 3 tested Semai children living in the rainforests of Peninsular Malaysia (3- to 4-year-olds, n = 60). Participants - across different ages, groups and methods - anticipated others' false-beliefs about object-location but not object-identity. Convergence in signature limits signalled that the early-developing efficient system involved minimal theory-of-mind. Chinese adults and older Semai children showed flexibility in their direct predictions. The flexible mindreading system in ascribing others' beliefs as such was task-sensitive and implicated maturational and cultural contributions. © 2015 The British Psychological Society.

Bridging the Gap between Human Resource Development and Adult Education: Part Two, the Critical Turn

Science.gov (United States)

Hatcher, Tim; Bowles, Tuere

2014-01-01

Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995). The…

5′ Rapid Amplification of cDNA Ends and Illumina MiSeq Reveals B Cell Receptor Features in Healthy Adults, Adults With Chronic HIV-1 Infection, Cord Blood, and Humanized Mice

Directory of Open Access Journals (Sweden)

Eric Waltari

2018-03-01

Full Text Available Using 5′ rapid amplification of cDNA ends, Illumina MiSeq, and basic flow cytometry, we systematically analyzed the expressed B cell receptor (BCR repertoire in 14 healthy adult PBMCs, 5 HIV-1+ adult PBMCs, 5 cord blood samples, and 3 HIS-CD4/B mice, examining the full-length variable region of μ, γ, α, κ, and λ chains for V-gene usage, somatic hypermutation (SHM, and CDR3 length. Adding to the known repertoire of healthy adults, Illumina MiSeq consistently detected small fractions of reads with high mutation frequencies including hypermutated μ reads, and reads with long CDR3s. Additionally, the less studied IgA repertoire displayed similar characteristics to that of IgG. Compared to healthy adults, the five HIV-1 chronically infected adults displayed elevated mutation frequencies for all μ, γ, α, κ, and λ chains examined and slightly longer CDR3 lengths for γ, α, and λ. To evaluate the reconstituted human BCR sequences in a humanized mouse model, we analyzed cord blood and HIS-CD4/B mice, which all lacked the typical SHM seen in the adult reference. Furthermore, MiSeq revealed identical unmutated IgM sequences derived from separate cell aliquots, thus for the first time demonstrating rare clonal members of unmutated IgM B cells by sequencing.

PPARg mRNA in the adult mouse hypothalamus: distribution and regulation in response to dietary challenges

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Yang eLiu

2015-09-01

Full Text Available Peroxisome proliferator-activated receptor gamma (PPARg is a ligand-activated transcription factor that was originally identified as a regulator of peroxisome proliferation and adipocyte differentiation. Emerging evidence suggests that functional PPARg signaling also occurs within the hypothalamus. However, the exact distribution and identities of PPARg-expressing hypothalamic cells remains under debate. The present study systematically mapped PPARg mRNA expression in the adult mouse brain using in situ hybridization histochemistry. PPARg mRNA was found to be expressed at high levels outside the hypothalamus including the neocortex, the olfactory bulb, the organ of the vasculosum of the lamina terminalis, and the subfornical organ. Within the hypothalamus, PPARg was present at moderate levels in the suprachiasmatic nucleus and the ependymal of the 3rd ventricle. In all examined feeding-related hypothalamic nuclei, PPARg was expressed at very low levels that were close to the limit of detection. Using qPCR techniques, we demonstrated that PPARg mRNA expression was upregulated in the suprachiasmatic nucleus in response to fasting. Double in situ hybridization further demonstrated that PPARg was primarily expressed in neurons. Collectively, our observations provide a comprehensive map of PPARg distribution and regulation in the intact adult mouse hypothalamus.

The Effect of Body Mass on Outdoor Adult Human Decomposition.

Science.gov (United States)

Roberts, Lindsey G; Spencer, Jessica R; Dabbs, Gretchen R

2017-09-01

Forensic taphonomy explores factors impacting human decomposition. This study investigated the effect of body mass on the rate and pattern of adult human decomposition. Nine males and three females aged 49-95 years ranging in mass from 73 to 159 kg who were donated to the Complex for Forensic Anthropology Research between December 2012 and September 2015 were included in this study. Kelvin accumulated degree days (KADD) were used to assess the thermal energy required for subjects to reach several total body score (TBS) thresholds: early decomposition (TBS ≥6.0), TBS ≥12.5, advanced decomposition (TBS ≥19.0), TBS ≥23.0, and skeletonization (TBS ≥27.0). Results indicate no significant correlation between body mass and KADD at any TBS threshold. Body mass accounted for up to 24.0% of variation in decomposition rate depending on stage, and minor differences in decomposition pattern were observed. Body mass likely has a minimal impact on postmortem interval estimation. © 2017 American Academy of Forensic Sciences.

Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults.

Science.gov (United States)

Ewen, Katherine A; Olesen, Inge A; Winge, Sofia B; Nielsen, Ana R; Nielsen, John E; Graem, Niels; Juul, Anders; Rajpert-De Meyts, Ewa

2013-01-01

Observations in patients with an activating mutation of fibroblast growth factor receptor 3 (FGFR3) suggest a role for FGFR3 signalling in promoting proliferation or survival of germ cells. In this study, we aimed to identify the FGFR3 subtype and the ontogeny of expression during human testis development and to ascertain whether FGFR3 signalling is linked to germ cell proliferation and the pathogenesis of testicular germ cell tumours (TGCTs) of young adult men. Using RT-PCR, immunohistochemistry and Western blotting, we examined 58 specimens of human testes throughout development for FGFR3 expression, and then compared expression of FGFR3 with proliferation markers (PCNA or Ki67). We also analysed for FGFR3 expression 30 TGCTs and 28 testes containing the tumour precursor cell, carcinoma in situ (CIS). Fetal and adult testes expressed exclusively the FGFR3IIIc isoform. FGFR3 protein expression was restricted to the cytoplasm/plasma membrane of spermatogonia and was most prevalent at mid-gestation, infancy and from puberty onwards. Phosphorylated (p)FGFR was detected in pre-spermatogonia at mid-gestation and in spermatogonia during puberty and in the adult testis. Throughout normal human testis development, expression of FGFR3 did not directly correlate with proliferation markers. In preinvasive CIS cells and in TGCTs, including classical seminoma and embryonal carcinoma, FGFR3IIIc was detected only in a small number of cells, with a heterogeneous expression pattern. FGFR3 is an excellent marker for human pre-/spermatogonia throughout development. Signalling through this receptor is likely associated with spermatogonial survival rather than proliferation. FGFR3 is not expressed in gonocytes and may not be essential to the aetiology of TGCTs stemming from CIS.

Norovirus-specific memory T cell responses in adult human donors

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Maria Malm

2016-10-01

Full Text Available Norovirus (NoV is a leading cause of acute gastroenteritis in people of all ages worldwide. NoV specific serum antibodies which block the binding of NoV virus-like particles (VLPs to the cell receptors have been thoroughly investigated. In contrast, only a few publications are available on the NoV capsid VP1 protein-specific T cell responses in humans naturally infected with the virus. Freshly isolated peripheral blood mononuclear cells of eight healthy adult human donors previously exposed to NoV were stimulated with purified VLPs derived from NoV GII.4-1999, GII.4-2012 (Sydney, and GI.3, and IFN-g production was measured by an ELISPOT assay. In addition, 76 overlapping synthetic peptides spanning the entire 539 amino acid sequence of GII.4 VP1 were pooled into two-dimensional matrices and used to identify putative T cell epitopes. Seven of the eight subjects produced IFN-g in response to the peptides and five subjects produced IFN-g in response to the VLPs of the same origin. In general, stronger T cell responses were induced with the peptides in each donor compared to the VLPs. A CD8+ T cell epitope in the shell domain of the VP1 (134SPSQVTMFPHIIVDVRQL151 was identified in two subjects, both having human leukocyte antigen (HLA-A*02:01 allele. To our knowledge, this is the first report using synthetic peptides to study NoV-specific T cell responses in human subjects and identify T cell epitopes.

Evaluating human papillomavirus vaccination programs in Canada: should provincial healthcare pay for voluntary adult vaccination?

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Smith? Robert J

2008-04-01

Full Text Available Abstract Background Recently, provincial health programs in Canada and elsewhere have begun rolling out vaccination against human papillomavirus for girls aged 9–13. While vaccination is voluntary, the cost of vaccination is waived, to encourage parents to have their daughters vaccinated. Adult women who are eligible for the vaccine may still receive it, but at a cost of approximately CAN$400. Given the high efficacy and immunogenicity of the vaccine, the possibility of eradicating targeted types of the virus may be feasible, assuming the vaccination programs are undertaken strategically. Methods We develop a mathematical model to describe the epidemiology of vaccination against human papillomavirus, accounting for a widespread childhood vaccination program that may be supplemented by voluntary adult vaccination. A stability analysis is performed to determine the stability of the disease-free equilibrium. The critical vaccine efficacy and immunogenicity thresholds are derived, and the minimum level of adult vaccination required for eradication of targeted types is determined. Results We demonstrate that eradication of targeted types is indeed feasible, although the burden of coverage for a childhood-only vaccination program may be high. However, if a small, but non-negligible, proportion of eligible adults can be vaccinated, then the possibility of eradication of targeted types becomes much more favourable. We provide a threshold for eradication in general communities and illustrate the results with numerical simulations. We also investigate the effects of suboptimal efficacy and immunogenicity and show that there is a critical efficacy below which eradication of targeted types is not possible. If eradication is possible, then there is a critical immunogenicity such that even 100% childhood vaccination will not eradicate the targeted types of the virus and must be supplemented with voluntary adult vaccination. However, the level of adult

Single cell electroporation for longitudinal imaging of synaptic structure and function in the adult mouse neocortex in vivo

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Stephane ePages

2015-04-01

Full Text Available Longitudinal imaging studies of neuronal structures in vivo have revealed rich dynamics in dendritic spines and axonal boutons. Spines and boutons are considered to be proxies for synapses. This implies that synapses display similar dynamics. However, spines and boutons do not always bear synapses, some may contain more than one, and dendritic shaft synapses have no clear structural proxies. In addition, synaptic strength is not always accurately revealed by just the size of these structures. Structural and functional dynamics of synapses could be studied more reliably using fluorescent synaptic proteins as markers for size and function. These proteins are often large and possibly interfere with circuit development, which renders them less suitable for conventional transfection or transgenesis methods such as viral vectors, in utero electroporation and germline transgenesis. Single cell electroporation has been shown to be a potential alternative for transfection of recombinant fluorescent proteins in adult cortical neurons. Here we provide proof of principle for the use of single cell electroporation to express and subsequently image fluorescently tagged synaptic proteins over days to weeks in vivo.

A method for high purity intestinal epithelial cell culture from adult human and murine tissues for the investigation of innate immune function.

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Graves, Christina L; Harden, Scott W; LaPato, Melissa; Nelson, Michael; Amador, Byron; Sorenson, Heather; Frazier, Charles J; Wallet, Shannon M

2014-12-01

Intestinal epithelial cells (IECs) serve as an important physiologic barrier between environmental antigens and the host intestinal immune system. Thus, IECs serve as a first line of defense and may act as sentinel cells during inflammatory insults. Despite recent renewed interest in IEC contributions to host immune function, the study of primary IEC has been hindered by lack of a robust culture technique, particularly for small intestinal and adult tissues. Here, a novel adaptation for culture of primary IEC is described for human duodenal organ donor tissue as well as duodenum and colon of adult mice. These epithelial cell cultures display characteristic phenotypes and are of high purity. In addition, the innate immune function of human primary IEC, specifically with regard to Toll-like receptor (TLR) expression and microbial ligand responsiveness, is contrasted with a commonly used intestinal epithelial cell line (HT-29). Specifically, TLR expression at the mRNA level and production of cytokine (IFNγ and TNFα) in response to TLR agonist stimulation is assessed. Differential expression of TLRs as well as innate immune responses to ligand stimulation is observed in human-derived cultures compared to that of HT-29. Thus, use of this adapted method to culture primary epithelial cells from adult human donors and from adult mice will allow for more appropriate studies of IECs as innate immune effectors. Published by Elsevier B.V.

FASH and MASH: female and male adult human phantoms based on polygon mesh surfaces: I. Development of the anatomy

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Cassola, V. F.; de Melo Lima, V. J.; Kramer, R.; Khoury, H. J.

2010-01-01

Among computational models, voxel phantoms based on computer tomographic (CT), nuclear magnetic resonance (NMR) or colour photographic images of patients, volunteers or cadavers have become popular in recent years. Although being true to nature representations of scanned individuals, voxel phantoms have limitations, especially when walled organs have to be segmented or when volumes of organs or body tissues, like adipose, have to be changed. Additionally, the scanning of patients or volunteers is usually made in supine position, which causes a shift of internal organs towards the ribcage, a compression of the lungs and a reduction of the sagittal diameter especially in the abdominal region compared to the regular anatomy of a person in the upright position, which in turn can influence organ and tissue absorbed or equivalent dose estimates. This study applies tools developed recently in the areas of computer graphics and animated films to the creation and modelling of 3D human organs, tissues, skeletons and bodies based on polygon mesh surfaces. Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been designed using software, such as MakeHuman, Blender, Binvox and ImageJ, based on anatomical atlases, observing at the same time organ masses recommended by the International Commission on Radiological Protection for the male and female reference adult in report no 89. 113 organs, bones and tissues have been modelled in the FASH and the MASH phantoms representing locations for adults in standing posture. Most organ and tissue masses of the voxelized versions agree with corresponding data from ICRP89 within a margin of 2.6%. Comparison with the mesh-based male RPI_AM and female RPI_AF phantoms shows differences with respect to the material used, to the software and concepts applied, and to the anatomies created.

FASH and MASH: female and male adult human phantoms based on polygon mesh surfaces: I. Development of the anatomy

International Nuclear Information System (INIS)

Cassola, V F; Kramer, R; Khoury, H J; De Melo Lima, V J

2010-01-01

Among computational models, voxel phantoms based on computer tomographic (CT), nuclear magnetic resonance (NMR) or colour photographic images of patients, volunteers or cadavers have become popular in recent years. Although being true to nature representations of scanned individuals, voxel phantoms have limitations, especially when walled organs have to be segmented or when volumes of organs or body tissues, like adipose, have to be changed. Additionally, the scanning of patients or volunteers is usually made in supine position, which causes a shift of internal organs towards the ribcage, a compression of the lungs and a reduction of the sagittal diameter especially in the abdominal region compared to the regular anatomy of a person in the upright position, which in turn can influence organ and tissue absorbed or equivalent dose estimates. This study applies tools developed recently in the areas of computer graphics and animated films to the creation and modelling of 3D human organs, tissues, skeletons and bodies based on polygon mesh surfaces. Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been designed using software, such as MakeHuman, Blender, Binvox and ImageJ, based on anatomical atlases, observing at the same time organ masses recommended by the International Commission on Radiological Protection for the male and female reference adult in report no 89. 113 organs, bones and tissues have been modelled in the FASH and the MASH phantoms representing locations for adults in standing posture. Most organ and tissue masses of the voxelized versions agree with corresponding data from ICRP89 within a margin of 2.6%. Comparison with the mesh-based male RPI A M and female RPI A F phantoms shows differences with respect to the material used, to the software and concepts applied, and to the anatomies created.

The organization and neural substrates of human memory.

Science.gov (United States)

Squire, L R

The neurology of memory has been illuminated by parallel studies of patients with circumscribed memory impairment and animal models of human amnesia. Human amnesia can occur as an isolated cognitive deficit that impairs the ability to learn new facts and episodes. In addition, memory can be affected for material learned many years prior to the onset of amnesia. The finding that some memory abilities are intact in amnesia (e.g., skill learning, word priming, and adaptation-level effects) has suggested that memory can be divided into two or more separate processes. Declarative memory affords the ability to store information explicitly and to retrieve it later as a conscious recollection. This form of memory depends on the integrity of the structures damaged in amnesia. Other, non-declarative kinds of memory afford the ability to change as the result of experience, but the information is available only through performance. Recent studies of a favorable human case provided strong evidence that the hippocampus is a critical component of the declarative memory system. Extensive convergent and divergent projections link the hippocampus to many areas of neocortex where processing and storage of new information is likely to occur. It is perhaps by way of these connections that the hippocampus operates upon and participates in declarative representations.

Isolation and characterization of multipotent progenitor cells from the Bowman's capsule of adult human kidneys.

Science.gov (United States)

Sagrinati, Costanza; Netti, Giuseppe Stefano; Mazzinghi, Benedetta; Lazzeri, Elena; Liotta, Francesco; Frosali, Francesca; Ronconi, Elisa; Meini, Claudia; Gacci, Mauro; Squecco, Roberta; Carini, Marco; Gesualdo, Loreto; Francini, Fabio; Maggi, Enrico; Annunziato, Francesco; Lasagni, Laura; Serio, Mario; Romagnani, Sergio; Romagnani, Paola

2006-09-01

Regenerative medicine represents a critical clinical goal for patients with ESRD, but the identification of renal adult multipotent progenitor cells has remained elusive. It is demonstrated that in human adult kidneys, a subset of parietal epithelial cells (PEC) in the Bowman's capsule exhibit coexpression of the stem cell markers CD24 and CD133 and of the stem cell-specific transcription factors Oct-4 and BmI-1, in the absence of lineage-specific markers. This CD24+CD133+ PEC population, which could be purified from cultured capsulated glomeruli, revealed self-renewal potential and a high cloning efficiency. Under appropriate culture conditions, individual clones of CD24+CD133+ PEC could be induced to generate mature, functional, tubular cells with phenotypic features of proximal and/or distal tubules, osteogenic cells, adipocytes, and cells that exhibited phenotypic and functional features of neuronal cells. The injection of CD24+CD133+ PEC but not of CD24-CD133- renal cells into SCID mice that had acute renal failure resulted in the regeneration of tubular structures of different portions of the nephron. More important, treatment of acute renal failure with CD24+CD133+ PEC significantly ameliorated the morphologic and functional kidney damage. This study demonstrates the existence and provides the characterization of a population of resident multipotent progenitor cells in adult human glomeruli, potentially opening new avenues for the development of regenerative medicine in patients who have renal diseases.

In vivo sensitivity of the embryonic and adult neural stem cell compartments to low-dose radiation

International Nuclear Information System (INIS)

Barazzuol, Lara; Jeggo, Penny A.

2016-01-01

The embryonic brain is radiation-sensitive, with cognitive deficits being observed after exposure to low radiation doses. Exposure of neonates to radiation can cause intracranial carcinogenesis. To gain insight into the basis underlying these outcomes, we examined the response of the embryonic, neonatal and adult brain to low-dose radiation, focusing on the neural stem cell compartments. This review summarizes our recent findings. At E13.5–14.5 the embryonic neocortex encompasses rapidly proliferating stem and progenitor cells. Exploiting mice with a hypomorphic mutation in DNA ligase IV (Lig4 Y288C ), we found a high level of DNA double-strand breaks (DSBs) at E14.5, which we attribute to the rapid proliferation. We observed endogenous apoptosis in Lig4 Y288C embryos and in WT embryos following exposure to low radiation doses. An examination of DSB levels and apoptosis in adult neural stem cell compartments, the subventricular zone (SVZ) and the subgranular zone (SGZ) revealed low DSB levels in Lig4 Y288C mice, comparable with the levels in differentiated neuronal tissues. We conclude that the adult SVZ does not incur high levels of DNA breakage, but sensitively activates apoptosis; apoptosis was less sensitively activated in the SGZ, and differentiated neuronal tissues did not activate apoptosis. P5/P15 mice showed intermediate DSB levels, suggesting that DSBs generated in the embryo can be transmitted to neonates and undergo slow repair. Interestingly, this analysis revealed a stage of high endogenous apoptosis in the neonatal SVZ. Collectively, these studies reveal that the adult neural stem cell compartment, like the embryonic counterpart, can sensitively activate apoptosis

Relative influence of human harvest, carnivores, and weather on adult female elk survival across western North America

Science.gov (United States)

Brodie, Jedediah; Johnson, Heather; Mitchell, Michael; Zager, Peter; Proffitt, Kelly; Hebblewhite, Mark; Kauffman, Matthew; Johnson, Bruce; Bissonette, John; Bishop, Chad; Gude, Justin; Herbert, Jeff; Hersey, Kent R.; Hurley, Mark; Lukacs, Paul M.; McCorquodale, Scott; McIntire, Eliot; Nowak, Josh; Sawyer, Hall; Smith, Douglas; White, P.J.

2013-01-01

Well-informed management of harvested species requires understanding how changing ecological conditions affect demography and population dynamics, information that is lacking for many species. We have limited understanding of the relative influence of carnivores, harvest, weather and forage availability on elk Cervus elaphus demography, despite the ecological and economic importance of this species. We assessed adult female survival, a key vital rate for population dynamics, from 2746 radio-collared elk in 45 populations across western North America that experience wide variation in carnivore assemblage, harvest, weather and habitat conditions. Proportional hazard analysis revealed that 'baseline' (i.e. not related to human factors) mortality was higher with very high winter precipitation, particularly in populations sympatric with wolves Canis lupus. Mortality may increase via nutritional stress and heightened vulnerability to predation in snowy winters. Baseline mortality was unrelated to puma Puma concolor presence, forest cover or summer forage productivity. Cause-specific mortality analyses showed that wolves and all carnivore species combined had additive effects on baseline elk mortality, but only reduced survival by <2%. When human factors were included, ‘total’ adult mortality was solely related to harvest; the influence of native carnivores was compensatory. Annual total mortality rates were lowest in populations sympatric with both pumas and wolves because managers reduced female harvest in areas with abundant or diverse carnivores. Mortality from native carnivores peaked in late winter and early spring, while harvest-induced mortality peaked in autumn. The strong peak in harvest-induced mortality during the autumn hunting season decreased as the number of native carnivore species increased. Synthesis and applications. Elevated baseline adult female elk mortality from wolves in years with high winter precipitation could affect elk abundance as

Peripheral nerve injury in developing rats reorganizes representation pattern in motor cortex.

OpenAIRE

Donoghue, J P; Sanes, J N

1987-01-01

We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stim...

Bridging the Gap between Human Resource Development and Adult Education: Part One, Assumptions, Definitions, and Critiques

Science.gov (United States)

Hatcher, Tim; Bowles, Tuere

2013-01-01

Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995).…

Comparative study of the chondrogenic potential of human bone marrow stromal cells, neonatal chondrocytes and adult chondrocytes

International Nuclear Information System (INIS)

Saha, Sushmita; Kirkham, Jennifer; Wood, David; Curran, Stephen; Yang, Xuebin

2010-01-01

Research highlights: → This study has characterised three different cell types under conditions similar to those used for autologous chondrocyte implantation (ACI) for applications in cartilage repair/regeneration. → Compared for the first time the chondrogenic potential of neonatal chondrocytes with human bone marrow stromal cells (HBMSCs) and adult chondrocytes. → Demonstrated that adult chondrocytes hold greatest potential for use in ACI based on their higher proliferation rates, lower alkaline phosphatise activity and enhanced expression of chondrogenic genes. → Demonstrated the need for chondroinduction as a necessary pre-requisite to efficient chondrogenesis in vitro and, by extrapolation, for cell based therapy (e.g. ACI or cartilage tissue engineering). -- Abstract: Cartilage tissue engineering is still a major clinical challenge with optimisation of a suitable source of cells for cartilage repair/regeneration not yet fully addressed. The aims of this study were to compare and contrast the differences in chondrogenic behaviour between human bone marrow stromal cells (HBMSCs), human neonatal and adult chondrocytes to further our understanding of chondroinduction relative to cell maturity and to identify factors that promote chondrogenesis and maintain functional homoeostasis. Cells were cultured in monolayer in either chondrogenic or basal medium, recapitulating procedures used in existing clinical procedures for cell-based therapies. Cell doubling time, morphology and alkaline phosphatase specific activity (ALPSA) were determined at different time points. Expression of chondrogenic markers (SOX9, ACAN and COL2A1) was compared via real time polymerase chain reaction. Amongst the three cell types studied, HBMSCs had the highest ALPSA in basal culture and lowest ALPSA in chondrogenic media. Neonatal chondrocytes were the most proliferative and adult chondrocytes had the lowest ALPSA in basal media. Gene expression analysis revealed a difference in the

Comparative study of the chondrogenic potential of human bone marrow stromal cells, neonatal chondrocytes and adult chondrocytes

Energy Technology Data Exchange (ETDEWEB)

Saha, Sushmita [Biomaterials and Tissue Engineering Group, Leeds Dental Institute, University of Leeds, LS29LU (United Kingdom); Kirkham, Jennifer [Biomineralisation Group, Leeds Dental Institute, University of Leeds, LS29LU (United Kingdom); NIHR Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Chapel Allerton Hospital, Leeds LS74SA (United Kingdom); Wood, David [Biomaterials and Tissue Engineering Group, Leeds Dental Institute, University of Leeds, LS29LU (United Kingdom); Curran, Stephen [Smith and Nephew Research Centre, YO105DF (United Kingdom); Yang, Xuebin, E-mail: X.B.Yang@leeds.ac.uk [Biomaterials and Tissue Engineering Group, Leeds Dental Institute, University of Leeds, LS29LU (United Kingdom); NIHR Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Chapel Allerton Hospital, Leeds LS74SA (United Kingdom)

2010-10-22

Research highlights: {yields} This study has characterised three different cell types under conditions similar to those used for autologous chondrocyte implantation (ACI) for applications in cartilage repair/regeneration. {yields} Compared for the first time the chondrogenic potential of neonatal chondrocytes with human bone marrow stromal cells (HBMSCs) and adult chondrocytes. {yields} Demonstrated that adult chondrocytes hold greatest potential for use in ACI based on their higher proliferation rates, lower alkaline phosphatise activity and enhanced expression of chondrogenic genes. {yields} Demonstrated the need for chondroinduction as a necessary pre-requisite to efficient chondrogenesis in vitro and, by extrapolation, for cell based therapy (e.g. ACI or cartilage tissue engineering). -- Abstract: Cartilage tissue engineering is still a major clinical challenge with optimisation of a suitable source of cells for cartilage repair/regeneration not yet fully addressed. The aims of this study were to compare and contrast the differences in chondrogenic behaviour between human bone marrow stromal cells (HBMSCs), human neonatal and adult chondrocytes to further our understanding of chondroinduction relative to cell maturity and to identify factors that promote chondrogenesis and maintain functional homoeostasis. Cells were cultured in monolayer in either chondrogenic or basal medium, recapitulating procedures used in existing clinical procedures for cell-based therapies. Cell doubling time, morphology and alkaline phosphatase specific activity (ALPSA) were determined at different time points. Expression of chondrogenic markers (SOX9, ACAN and COL2A1) was compared via real time polymerase chain reaction. Amongst the three cell types studied, HBMSCs had the highest ALPSA in basal culture and lowest ALPSA in chondrogenic media. Neonatal chondrocytes were the most proliferative and adult chondrocytes had the lowest ALPSA in basal media. Gene expression analysis revealed

Histomorphometry and cortical robusticity of the adult human femur.

Science.gov (United States)

Miszkiewicz, Justyna Jolanta; Mahoney, Patrick

2018-01-13

Recent quantitative analyses of human bone microanatomy, as well as theoretical models that propose bone microstructure and gross anatomical associations, have started to reveal insights into biological links that may facilitate remodeling processes. However, relationships between bone size and the underlying cortical bone histology remain largely unexplored. The goal of this study is to determine the extent to which static indicators of bone remodeling and vascularity, measured using histomorphometric techniques, relate to femoral midshaft cortical width and robusticity. Using previously published and new quantitative data from 450 adult human male (n = 233) and female (n = 217) femora, we determine if these aspects of femoral size relate to bone microanatomy. Scaling relationships are explored and interpreted within the context of tissue form and function. Analyses revealed that the area and diameter of Haversian canals and secondary osteons, and densities of secondary osteons and osteocyte lacunae from the sub-periosteal region of the posterior midshaft femur cortex were significantly, but not consistently, associated with femoral size. Cortical width and bone robusticity were correlated with osteocyte lacunae density and scaled with positive allometry. Diameter and area of osteons and Haversian canals decreased as the width of cortex and bone robusticity increased, revealing a negative allometric relationship. These results indicate that microscopic products of cortical bone remodeling and vascularity are linked to femur size. Allometric relationships between more robust human femora with thicker cortical bone and histological products of bone remodeling correspond with principles of bone functional adaptation. Future studies may benefit from exploring scaling relationships between bone histomorphometric data and measurements of bone macrostructure.

Relative influence of human harvest, carnivores, and weather on adult female elk survival across western North America

Science.gov (United States)

Brodie, Jedediah; Johnson, Heather; Mitchell, Michael; Zager, Peter; Proffitt, Kelly; Hebblewhite, Mark; Kauffman, Matthew; Johnson, Bruce; Bissonette, John; Bishop, Chad; Gude, Justin; Herbert, Jeff; Hersey, Kent R.; Hurley, Mark; Lukacs, Paul M.; McCorquodale, Scott; McIntire, Eliot; Nowak, Josh; Sawyer, Hall; Smith, Douglas; White, P.J.

2013-01-01

Well-informed management of harvested species requires understanding how changing ecological conditions affect demography and population dynamics, information that is lacking for many species. We have limited understanding of the relative influence of carnivores, harvest, weather and forage availability on elk Cervus elaphus demography, despite the ecological and economic importance of this species. We assessed adult female survival, a key vital rate for population dynamics, from 2746 radio-collared elk in 45 populations across western North America that experience wide variation in carnivore assemblage, harvest, weather and habitat conditions. Proportional hazard analysis revealed that 'baseline' (i.e. not related to human factors) mortality was higher with very high winter precipitation, particularly in populations sympatric with wolves Canis lupus. Mortality may increase via nutritional stress and heightened vulnerability to predation in snowy winters. Baseline mortality was unrelated to puma Puma concolor presence, forest cover or summer forage productivity. Cause-specific mortality analyses showed that wolves and all carnivore species combined had additive effects on baseline elk mortality, but only reduced survival by baseline adult female elk mortality from wolves in years with high winter precipitation could affect elk abundance as winters across the western US become drier and wolves recolonize portions of the region. In the absence of human harvest, wolves had additive, although limited, effects on mortality. However, human harvest, and its apparent use by managers to offset predation, primarily controls overall variation in adult female mortality. Altering harvest quotas is thus a strong tool for offsetting impacts of carnivore recolonization and shifting weather patterns on elk across western North America.

Effects of low-dose X-irradiation on the developing brain, 19. Developmental disturbance of cerebral neocortex in rats. gamma. -irradiated on day 15 of gestation

Energy Technology Data Exchange (ETDEWEB)

Hoshino, K.; Fukui, Y.; Hayasaka, I.; Hayasaka, S.; Ito, Y.; Kameyama, Y.

1987-03-01

F344/DuCrj rats were irradiated with gamma-rays in a single dose of either 0.27 or 0.48 Gy at day 15 of gestation. Their neonates were autopsied at week 6 or 12 after birth for morphological observation of the cerebrum. The weight of brain had significantly decreased in a dose-dependent manner at weeks 6 and 12 in both irradiated groups. The thickness of the neocortex had also significantly decreased in both groups at week 6; however, the significant decrease at week 12 was confined to the group with 0.48 Gy. There was no difference in the cell density between the groups. Observations for dendrites in the base of pyramidal cells of the 5th layer of cerebral cortex showed that irradiation influenced the decrease in the number of dendrites directly arising in the reticulum, but did not influence the branching index. Electron microscopy showed that irradiation with 0.48 Gy influenced neither synapse density nor synaptic length.

Role for astroglial α1-adrenoreceptors in gliotransmission and control of synaptic plasticity in the neocortex

Directory of Open Access Journals (Sweden)

Yuriy ePankratov

2015-06-01

Full Text Available Communication between neuronal and glial cells is thought to be very important for many brain functions. Acting via release of gliotransmitters, astrocytes can modulate synaptic strength. The mechanisms underlying gliotransmission remain uncertain with exocytosis being the most intriguing and debated pathway.We demonstrate that astroglial α1-adrenoreceptors are very sensitive to noradrenaline and make a significant contribution to intracellular Ca2+-signalling in layer 2/3 neocortical astrocytes. We also show that astroglial α1-adrenoreceptors are prone to desensitization upon prolonged exposure to noradrenaline.We show that within neocortical slices, α-1adrenoreceptors can activate vesicular release of ATP and D-serine from cortical astrocytes which initiate a burst of ATP receptor-mediated currents in adjacent pyramidal neurons. These purinergic currents can be inhibited by intracellular perfusion of astrocytes with Tetanus Toxin light chain, verifying their origin via astroglial exocytosis.We show that α1 adrenoreceptor-activated release of gliotransmitters is important for the induction of synaptic plasticity in the neocortex:long-term potentiation (LTP of neocortical excitatory synaptic potentials can be abolished by the selective α1-adrenoreceptor antagonist terazosin. We show that weak sub-threshold theta-burst stimulation can induce LTP when astrocytes are additionally activated by 1 μM noradrenaline. This facilitation is dependent on the activation of neuronal ATP receptors and is abolished in neocortical slices from dn-SNARE mice which have impaired glial exocytosis. Importantly, facilitation of LTP by noradrenaline can be significantly reduced by perfusion of individual astrocytes with Tetanus Toxin. Our results strongly support the physiological importance of astroglial adrenergic signalling and exocytosis of gliotransmitters for modulation of synaptic transmission and plasticity .

Characterization of human coronavirus etiology in Chinese adults with acute upper respiratory tract infection by real-time RT-PCR assays.

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Roujian Lu

Full Text Available BACKGROUND: In addition to SARS associated coronaviruses, 4 non-SARS related human coronaviruses (HCoVs are recognized as common respiratory pathogens. The etiology and clinical impact of HCoVs in Chinese adults with acute upper respiratory tract infection (URTI needs to be characterized systematically by molecular detection with excellent sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we detected 4 non-SARS related HCoV species by real-time RT-PCR in 981 nasopharyngeal swabs collected from March 2009 to February 2011. All specimens were also tested for the presence of other common respiratory viruses and newly identified viruses, human metapneumovirus (hMPV and human bocavirus (HBoV. 157 of the 981 (16.0% nasopharyngeal swabs were positive for HCoVs. The species detected were 229E (96 cases, 9.8%, OC43 (42 cases, 4.3%, HKU1 (16 cases, 1.6% and NL63 (11 cases, 1.1%. HCoV-229E was circulated in 21 of the 24 months of surveillance. The detection rates for both OC43 and NL63 were showed significantly year-to-year variation between 2009/10 and 2010/11, respectively (P<0.001 and P = 0.003, and there was a higher detection frequency of HKU1 in patients aged over 60 years (P = 0.03. 48 of 157(30.57% HCoV positive patients were co-infected. Undifferentiated human rhinoviruses and influenza (Flu A were the most common viruses detected (more than 35% in HCoV co-infections. Respiratory syncytial virus (RSV, human parainfluenza virus (PIV and HBoV were detected in very low rate (less than 1% among adult patients with URTI. CONCLUSIONS/SIGNIFICANCE: All 4 non-SARS-associated HCoVs were more frequently detected by real-time RT-PCR assay in adults with URTI in Beijing and HCoV-229E led to the most prevalent infection. Our study also suggested that all non-SARS-associated HCoVs contribute significantly to URTI in adult patients in China.

Prevalence of antibody to adult T-cell leukemia virus-associated antigens (ATLA) in Japanese monkeys and other non-human primates.

Science.gov (United States)

Hayami, M; Komuro, A; Nozawa, K; Shotake, T; Ishikawa, K; Yamamoto, K; Ishida, T; Honjo, S; Hinuma, Y

1984-02-15

The prevalence of adult T-cell-leukemia virus (ATLV) infection was examined in Japanese monkeys living naturally in various parts of Japan and in other species of non-human primates imported into and kept in Japan. Sera of 2,650 Japanese monkeys from 41 troops throughout Japan were tested. High incidences of anti-ATLV-associated antigen (ATLA)-positive monkeys were found in most troops, not only in the endemic area of human ATL(Southwestern Japan), but also in non-endemic areas. The incidence of sero-positive individuals increased gradually with age, reaching a maximum when the animals became adult, indicating age dependency, like that found by epidemiological studies on humans. Anti-ATLA antibodies were also detected in 90 of 815 sera of imported non-human primates of 33 species other than Japanese monkeys. All the anti-ATLA sero-positive monkeys were Catarrhines (Old World monkeys), mainly macaques of Asian origin. Some sero-positive monkeys were also found among animals of African origin, but no antibody was detected in Prosimians and Platyrrhines (New World monkeys). The clear-cut difference between the geographical distribution of sero-positive simians and that of humans indicates the improbability of direct transmission of ATLV from simians to humans.

Isolation of mineralizing Nestin+ Nkx6.1+ vascular muscular cells from the adult human spinal cord

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Guillon Hélène

2011-10-01

Full Text Available Abstract Background The adult central nervous system (CNS contains different populations of immature cells that could possibly be used to repair brain and spinal cord lesions. The diversity and the properties of these cells in the human adult CNS remain to be fully explored. We previously isolated Nestin+ Sox2+ neural multipotential cells from the adult human spinal cord using the neurosphere method (i.e. non adherent conditions and defined medium. Results Here we report the isolation and long term propagation of another population of Nestin+ cells from this tissue using adherent culture conditions and serum. QPCR and immunofluorescence indicated that these cells had mesenchymal features as evidenced by the expression of Snai2 and Twist1 and lack of expression of neural markers such as Sox2, Olig2 or GFAP. Indeed, these cells expressed markers typical of smooth muscle vascular cells such as Calponin, Caldesmone and Acta2 (Smooth muscle actin. These cells could not differentiate into chondrocytes, adipocytes, neuronal and glial cells, however they readily mineralized when placed in osteogenic conditions. Further characterization allowed us to identify the Nkx6.1 transcription factor as a marker for these cells. Nkx6.1 was expressed in vivo by CNS vascular muscular cells located in the parenchyma and the meninges. Conclusion Smooth muscle cells expressing Nestin and Nkx6.1 is the main cell population derived from culturing human spinal cord cells in adherent conditions with serum. Mineralization of these cells in vitro could represent a valuable model for studying calcifications of CNS vessels which are observed in pathological situations or as part of the normal aging. In addition, long term propagation of these cells will allow the study of their interaction with other CNS cells and their implication in scar formation during spinal cord injury.

Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

International Nuclear Information System (INIS)

Manceur, Aziza P.; Tseng, Michael; Holowacz, Tamara; Witterick, Ian; Weksberg, Rosanna; McCurdy, Richard D.; Warsh, Jerry J.; Audet, Julie

2011-01-01

The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

Impact of antibiotic use in adult dairy cows on antimicrobial resistance of veterinary and human pathogens: a comprehensive review.

Science.gov (United States)

Oliver, Stephen P; Murinda, Shelton E; Jayarao, Bhushan M

2011-03-01

Antibiotics have saved millions of human lives, and their use has contributed significantly to improving human and animal health and well-being. Use of antibiotics in food-producing animals has resulted in healthier, more productive animals; lower disease incidence and reduced morbidity and mortality in humans and animals; and production of abundant quantities of nutritious, high-quality, and low-cost food for human consumption. In spite of these benefits, there is considerable concern from public health, food safety, and regulatory perspectives about the use of antimicrobials in food-producing animals. Over the last two decades, development of antimicrobial resistance resulting from agricultural use of antibiotics that could impact treatment of diseases affecting the human population that require antibiotic intervention has become a significant global public health concern. In the present review, we focus on antibiotic use in lactating and nonlactating cows in U.S. dairy herds, and address four key questions: (1) Are science-based data available to demonstrate antimicrobial resistance in veterinary pathogens that cause disease in dairy cows associated with use of antibiotics in adult dairy cows? (2) Are science-based data available to demonstrate that antimicrobial resistance in veterinary pathogens that cause disease in adult dairy cows impacts pathogens that cause disease in humans? (3) Does antimicrobial resistance impact the outcome of therapy? (4) Are antibiotics used prudently in the dairy industry? On the basis of this review, we conclude that scientific evidence does not support widespread, emerging resistance among pathogens isolated from dairy cows to antibacterial drugs even though many of these antibiotics have been used in the dairy industry for treatment and prevention of disease for several decades. However, it is clear that use of antibiotics in adult dairy cows and other food-producing animals does contribute to increased antimicrobial resistance

Distinct muscarinic acetylcholine receptor subtypes mediate pre- and postsynaptic effects in rat neocortex

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Gigout Sylvain

2012-04-01

Full Text Available Abstract Background Cholinergic transmission has been implicated in learning, memory and cognition. However, the cellular effects induced by muscarinic acetylcholine receptors (mAChRs activation are poorly understood in the neocortex. We investigated the effects of the cholinergic agonist carbachol (CCh and various agonists and antagonists on neuronal activity in rat neocortical slices using intracellular (sharp microelectrode and field potential recordings. Results CCh increased neuronal firing but reduced synaptic transmission. The increase of neuronal firing was antagonized by pirenzepine (M1/M4 mAChRs antagonist but not by AF-DX 116 (M2/M4 mAChRs antagonist. Pirenzepine reversed the depressant effect of CCh on excitatory postsynaptic potential (EPSP but had marginal effects when applied before CCh. AF-DX 116 antagonized the depression of EPSP when applied before or during CCh. CCh also decreased the paired-pulse inhibition of field potentials and the inhibitory conductances mediated by GABAA and GABAB receptors. The depression of paired-pulse inhibition was antagonized or prevented by AF-DX 116 or atropine but only marginally by pirenzepine. The inhibitory conductances were unaltered by xanomeline (M1/M4 mAChRs agonist, yet the CCh-induced depression was antagonized by AF-DX 116. Linopirdine, a selective M-current blocker, mimicked the effect of CCh on neuronal firing. However, linopirdine had no effect on the amplitude of EPSP or on the paired-pulse inhibition, indicating that M-current is involved in the increase of neuronal excitability but neither in the depression of EPSP nor paired-pulse inhibition. Conclusions These data indicate that the three effects are mediated by different mAChRs, the increase in firing being mediated by M1 mAChR, decrease of inhibition by M2 mAChR and depression of excitatory transmission by M4 mAChR. The depression of EPSP and increase of neuronal firing might enhance the signal-to-noise ratio, whereas the

TP53 mutation and human papilloma virus status of oral squamous cell carcinomas in young adult patients

NARCIS (Netherlands)

Braakhuis, B.J.M.; Rietbergen, M.M.; Buijze, M.; Snijders, P.J.F.; Bloemena, E.; Brakenhoff, R.H.; Leemans, C.R.

2014-01-01

Objective Little is known about the molecular carcinogenesis of oral squamous cell carcinoma (OSCC) in young adult patients. The aim of this study was to investigate the detailed TP53 mutation and human papilloma virus (HPV) status of OSCC in patients, younger than 45 years. Methods TP53 mutations

Modeling cortical circuits.

Energy Technology Data Exchange (ETDEWEB)

Rohrer, Brandon Robinson; Rothganger, Fredrick H.; Verzi, Stephen J.; Xavier, Patrick Gordon

2010-09-01

The neocortex is perhaps the highest region of the human brain, where audio and visual perception takes place along with many important cognitive functions. An important research goal is to describe the mechanisms implemented by the neocortex. There is an apparent regularity in the structure of the neocortex [Brodmann 1909, Mountcastle 1957] which may help simplify this task. The work reported here addresses the problem of how to describe the putative repeated units ('cortical circuits') in a manner that is easily understood and manipulated, with the long-term goal of developing a mathematical and algorithmic description of their function. The approach is to reduce each algorithm to an enhanced perceptron-like structure and describe its computation using difference equations. We organize this algorithmic processing into larger structures based on physiological observations, and implement key modeling concepts in software which runs on parallel computing hardware.

Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis.

Science.gov (United States)

Desdoits-Lethimonier, C; Lesné, L; Gaudriault, P; Zalko, D; Antignac, J P; Deceuninck, Y; Platel, C; Dejucq-Rainsford, N; Mazaud-Guittot, S; Jégou, B

2017-07-01

Are bisphenol A (BPA) and BPA analogs (BPA-A) safe for male human reproductive function? The endocrine function of human testes explants [assessed by measuring testosterone and insulin-like factor 3 (INSL3)] was impacted by exposure of the human adult testis explants to BPA/BPA-A. The few epidemiologic studies performed suggest that bisphenols have potential endocrine disruptive properties, but they did not identify clear and direct patterns of endocrine disruption. Adult human testis explants in culture were exposed to BPA and the analogs bisphenol F (BPF), bisphenol S (BPS), bisphenol E (BPE), bisphenol B (BPB) and bisphenol A diglycidyl ether (BADGE) at 10-9-10-5 M for 24 or 48 h. Human adult testes were obtained from prostate cancer patients who had no hormone therapy, or from multiorgan donors. After ex vivo exposure to the investigated bisphenols, the measured outcomes were related to histopathology (gross morphology and germ cell viability determined by anti-caspase three immunohistochemistry), and the levels of testosterone, INSL3 and inhibin B were measured using immunoassays. The levels of mRNA encoding key enzymes of bisphenol biotransformation were investigated by quantitative PCR: UGT2B15 UDP (glucuronosyltransferase two family, polypeptide B15), GUSB (glucuronidase beta), SULT1A1 and 3 (sulfotransferase family 1 A member 1 and 3) and STS (steroid sulfatase). A significant dose-dependent inhibition was found between testosterone levels measured in the culture medium and concentrations of BPA (P = 0.00778 at 24 h and P = 0.0291 at 48 h), BPE (P = 0.039) and BPF (P = 0.00663). The observed BPA and BPA-A-induced inhibition of testosterone production varied according to duration of exposure and BPA/BPA-A concentrations. BPA (10-9 M; P bisphenols. N/A. Environmental compounds cannot be deliberately administered to men, justifying the use of an ex vivo approach. A relatively low number of testes samples were available for analysis (n = 3, except for

The mammalian neocortical pyramidal cell: a new theory on prenatal development

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Miguel eMarín-Padilla

2014-01-01

Full Text Available Mammals’ new cerebral cortex (neocortex and the new type of pyramidal neuron are mammalian innovations that have evolved for operating their increasing motor capabilities using essentially analogous anatomical and neural makeups. The human neocortex starts to develop in the 6-week-old embryo with the establishment of a primordial cortical organization that resembles the primitive cortices of amphibian and reptiles that operated his early motor activities. From the 8th to the 15th week of age, the new pyramidal neurons, of ependymal origin, are progressively incorporated within this primordial cortex forming a cellular plate that divide its components into those above it (neocortex first lamina and those below it (neocortex subplate elements. From the 16th week of age to birth and postnatally, the new pyramidal neurons continue to elongate functionally their apical dendrite by adding synaptic membrane to incorporate the needed sensory information for operating the animal muscular activities. The new pyramidal neuron’ distinguishing feature is the capacity of elongating anatomically and functionally its apical dendrite (its main receptive surface without losing its original attachment to first lamina or the location of its soma retaining its essential nature. The number of pyramidal cell functional strata established in the motor cortex increases and reflects each mammalian species motor capabilities: the hedgehog needs 2 pyramidal cell functional strata to carry out all its motor activities, the mouse three, cat four, primates 5 and humans 6. The presence of six pyramidal cell functional strata distinguish the human motor cortex from that of others primates. Homo sapiens represent a new evolutionary stage that have transformed his primate brain for operating his unique motor capabilities, such as speaking, writing, painting, sculpturing including thinking as a premotor activity.

Specific metabolomics adaptations define a differential regional vulnerability in the adult human cerebral cortex

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Rosanna Cabré

2016-12-01

Full Text Available Brain neurons offer diverse responses to stresses and detrimental factors during development and aging, and as a result of both neurodegenerative and neuropsychiatric disorders. This multiplicity of responses can be ascribed to the great diversity among neuronal populations. Here we have determined the metabolomic profile of three healthy adult human brain regions—entorhinal cortex, hippocampus, and frontal cortex—using mass spectrometry-based technologies. Our results show the existence of a lessened energy demand, mitochondrial stress, and lower one-carbon metabolism (particularly restricted to the methionine cycle specifically in frontal cortex. These findings, along with the better antioxidant capacity and lower mTOR signaling also seen in frontal cortex, suggest that this brain region is especially resistant to stress compared to the entorhinal cortex and hippocampus, which are more vulnerable regions. Globally, our results show the presence of specific metabolomics adaptations in three mature, healthy human brain regions, confirming the existence of cross-regional differences in cell vulnerability in the human cerebral cortex.

Dog Walking, the Human-Animal Bond and Older Adults' Physical Health.

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Curl, Angela L; Bibbo, Jessica; Johnson, Rebecca A

2017-10-01

This study explored the associations between dog ownership and pet bonding with walking behavior and health outcomes in older adults. We used data from the 12th wave (2012) of the Health and Retirement Study which included an experimental human-animal interaction module. Ordinary least squares regression and binary logistic regression models controlling for demographic variables were used to answer the research questions. Dog walking was associated with lower body mass index, fewer activities of daily living limitations, fewer doctor visits, and more frequent moderate and vigorous exercise. People with higher degrees of pet bonding were more likely to walk their dog and to spend more time walking their dog each time, but they reported walking a shorter distance with their dog than those with weaker pet bonds. Dog ownership was not associated with better physical health or health behaviors. This study provides evidence for the association between dog walking and physical health using a large, nationally representative sample. The relationship with one's dog may be a positive influence on physical activity for older adults. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Radiation dose estimates for adults and newborns from tungsten-178: based on distribution data in adult and infant animals

International Nuclear Information System (INIS)

Wiles, H.; Lacy, J.; LeBlanc, A.; Bricker, J.; Watson, E.; Stabin, M.

1987-01-01

Biodistribution and retention of tungsten-178 ( 178 W) were studied in adult and infant animals in order to extrapolate radiation dose estimates to human newborns and adults. Whole body retention and organ distribution of 178 W were determined at 0.5, 2, 8, 24 and 48 hours after blood-pool injection in infant and adult rats. Percent whole body retention and percent organ uptake per gram of tissue were higher in infant than adult rats at each time interval. When extrapolated to humans on the basis of percent injected activity kilogram per gram, most organs, except bone and kidney, showed higher uptake in newborns than adults. Total body radiation dose estimates for humans from 178 w based on these data were: 0.93 mGy/MBq (3.4 rad/mCi) for newborns and 0.024 mGy/MBq (0.089 rad/mCi) for adults. 13 refs.; 5 tabs

The role of REM theta activity in emotional memory

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Isabel Camilla Hutchison

2015-10-01

Full Text Available While NREM sleep has been strongly implicated in the reactivation and consolidation of memory traces, the role of REM sleep remains unclear. A growing body of research on humans and animals provide behavioral evidence for a role of REM sleep in the strengthening and modulation of emotional memories. Theta activity – which describes low frequency oscillations in the local field potential within the hippocampus, amygdala and neocortex – is a prominent feature of both wake and REM sleep in humans and rodents. Theta coherence between the hippocampus and amygdala drives large-scale PGO waves, the density of which predicts increases in plasticity-related gene expression. This could potentially facilitate the processing of emotional memory traces within the hippocampus during REM sleep. Further, the timing of hippocampal activity in relation to theta phase is vital in determining subsequent potentiation of neuronal activity. This could allow the emotionally modulated strengthening of novel and the gradual weakening of consolidated hippocampal memory traces observed in both wake and REM sleep. Hippocampal theta activity is also correlated with REM sleep acetylcholine levels – which are thought to reduce hippocampal afferent inputs in the neocortex. The additional low levels of noradrenaline during REM sleep, which facilitate recurrent activation within the neocortex, could allow the integration of novel memory traces previously consolidated during NREM sleep. We therefore propose that REM sleep mediates the prioritized processing of emotional memories within the hippocampus, the integration of previously consolidated memory traces within the neocortex, as well as the disengagement of consolidated neocortical memory traces from the hippocampus.

Gastrointestinal absorption of plutonium and uranium in fed and fasted adult baboons and mice: application to humans

International Nuclear Information System (INIS)

Bhattacharyya, M.H.; Larsen, R.P.; Oldham, R.D.; Cohen, N.; Ralston, L.G.; Moretti, E.S.; Ayres, L.

1989-01-01

Gastrointestinal (GI) absorption values of plutonium and uranium were determined in fed and fasted adult baboons and mice. For both baboons and mice, the GI absorptions of plutonium and uranium were 10 to 20 times higher in 24 h fasted animals than in fed ones. For plutonium, GI absorption values in baboons were almost identical to those in mice for both fed and fasted conditions, and values for fed animals agreed with estimates for humans. For uranium, GI absorption values in fed and fasted baboons were 6 to 7 times higher than those in mice, and agreed well with those fed and fasted humans. For one baboon that was not given its morning meal, plutonium absorption 2 h after the start of the active phase was the same as that in the 24 h fasted animals. In contrast, for baboons that received a morning meal, plutonium absorption did not rise to the value of 24 h fasted baboons even 8 h after the meal. We conclude that GI absorption values for plutonium and uranium in adult baboons are good estimates of the values in humans and that the values for the fasted condition should be used to set standards for oral exposure of persons in the workplace. (author)

CCL2 binding is CCR2 independent in primary adult human astrocytes.

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Fouillet, A; Mawson, J; Suliman, O; Sharrack, B; Romero, I A; Woodroofe, M N

2012-02-09

Chemokines are low relative molecular mass proteins, which have chemoattractant actions on many cell types. The chemokine, CCL2, has been shown to play a major role in the recruitment of monocytes in central nervous system (CNS) lesions in multiple sclerosis (MS). Since resident astrocytes constitute a major source of chemokine synthesis including CCL2, we were interested to assess the regulation of CCL2 by astrocytes. We showed that CCL2 bound to the cell surface of astrocytes and binding was not modulated by inflammatory conditions. However, CCR2 protein was not detected nor was activation of the classical CCR2 downstream signaling pathways. Recent studies have shown that non-signaling decoy chemokine receptors bind and modulate the expression of chemokines at site of inflammation. Here, we show that the D6 chemokine decoy receptor is constitutively expressed by primary human adult astrocytes at both mRNA and protein level. In addition, CCL3, which binds to D6, but not CCL19, which does not bind to D6, displaced CCL2 binding to astrocytes; indicating that CCL2 may bind to this cell type via the D6 receptor. Our results suggest that CCL2 binding to primary adult human astrocytes is CCR2-independent and is likely to be mediated via the D6 decoy chemokine receptor. Therefore we propose that astrocytes are implicated in both the establishment of chemokine gradients for the migration of leukocytes into and within the CNS and in the regulation of CCL2 levels at inflammatory sites in the CNS. Copyright © 2011 Elsevier B.V. All rights reserved.

In vivo sensitivity of the embryonic and adult neural stem cell compartments to low-dose radiation.

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Barazzuol, Lara; Jeggo, Penny A

2016-08-01

The embryonic brain is radiation-sensitive, with cognitive deficits being observed after exposure to low radiation doses. Exposure of neonates to radiation can cause intracranial carcinogenesis. To gain insight into the basis underlying these outcomes, we examined the response of the embryonic, neonatal and adult brain to low-dose radiation, focusing on the neural stem cell compartments. This review summarizes our recent findings. At E13.5-14.5 the embryonic neocortex encompasses rapidly proliferating stem and progenitor cells. Exploiting mice with a hypomorphic mutation in DNA ligase IV (Lig4(Y288C) ), we found a high level of DNA double-strand breaks (DSBs) at E14.5, which we attribute to the rapid proliferation. We observed endogenous apoptosis in Lig4(Y288C) embryos and in WT embryos following exposure to low radiation doses. An examination of DSB levels and apoptosis in adult neural stem cell compartments, the subventricular zone (SVZ) and the subgranular zone (SGZ) revealed low DSB levels in Lig4(Y288C) mice, comparable with the levels in differentiated neuronal tissues. We conclude that the adult SVZ does not incur high levels of DNA breakage, but sensitively activates apoptosis; apoptosis was less sensitively activated in the SGZ, and differentiated neuronal tissues did not activate apoptosis. P5/P15 mice showed intermediate DSB levels, suggesting that DSBs generated in the embryo can be transmitted to neonates and undergo slow repair. Interestingly, this analysis revealed a stage of high endogenous apoptosis in the neonatal SVZ. Collectively, these studies reveal that the adult neural stem cell compartment, like the embryonic counterpart, can sensitively activate apoptosis. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Optical and Biometric Characteristics of Anisomyopia in Human Adults

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Tian, Yibin; Tarrant, Janice; Wildsoet, Christine F.

2011-01-01

Purpose To investigate the role of higher order optical aberrations and thus retinal image degradation in the development of myopia, through the characterization of anisomyopia in human adults in terms of their optical and biometric characteristics. Methods The following data were collected from both eyes of fifteen young adult anisometropic myopes and sixteen isometropic myopes: subjective and objective refractive errors, corneal power and shape, monochromatic optical aberrations, anterior chamber depth, lens thickness, vitreous chamber depth, and best corrected visual acuity. Monochromatic aberrations were analyzed in terms of their higher order components, and further analyzed in terms of 31 optical quality metrics. Interocular differences for the two groups (anisomyopes vs. isomyopes) were compared and the relationship between measured ocular parameters and refractive errors also analyzed across all eyes. Results As expected, anisomyopes and isomyopes differed significantly in terms of interocular differences in vitreous chamber depth, axial length and refractive error. However, interocular differences in other optical properties showed no significant intergroup differences. Overall, higher myopia was associated with deeper anterior and vitreous chambers, higher astigmatism, more prolate corneas, and more positive spherical aberration. Other measured optical and biometric parameters were not significantly correlated with spherical refractive error, although some optical quality metrics and corneal astigmatism were significantly correlated with refractive astigmatism. Conclusions An optical cause for anisomyopia related to increased higher order aberrations is not supported by our data. Corneal shape changes and increased astigmatism in more myopic eyes may be a by-product of the increased anterior chamber growth in these eyes; likewise, the increased positive spherical aberration in more myopic eyes may be a product of myopic eye growth. PMID:21797915

Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

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Manceur, Aziza P. [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Tseng, Michael [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Holowacz, Tamara [Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Witterick, Ian [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Department of Otolaryngology, Head and Neck Surgery, University of Toronto, ON (Canada); Weksberg, Rosanna [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); McCurdy, Richard D. [The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); Warsh, Jerry J. [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Audet, Julie, E-mail: julie.audet@utoronto.ca [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada)

2011-09-10

The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

Atrial Fibrillation associated chromosome 4q25 variants are not associated with PITX2c expression in human adult left atrial appendages.

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Shamone R Gore-Panter

Full Text Available Atrial Fibrillation (AF, the most common sustained arrhythmia, has a strong genetic component, but the mechanism by which common genetic variants lead to increased AF susceptibility is unknown. Genome-wide association studies (GWAS have identified that the single nucleotide polymorphisms (SNPs most strongly associated with AF are located on chromosome 4q25 in an intergenic region distal to the PITX2 gene. Our objective was to determine whether the AF-associated SNPs on chromosome 4q25 were associated with PITX2c expression in adult human left atrial appendages. Analysis of a lone AF GWAS identified four independent AF risk SNPs at chromosome 4q25. Human adult left atrial appendage tissue was obtained from 239 subjects of European Ancestry and used for SNP analysis of genomic DNA and determination of PITX2c RNA expression levels by quantitative PCR. Subjects were divided into three groups based on their history of AF and pre-operative rhythm. AF rhythm subjects had higher PITX2c expression than those with history of AF but in sinus rhythm. PITX2c expression was not associated with the AF risk SNPs in human adult left atrial appendages in all subjects combined or in each of the three subgroups. However, we identified seven SNPs modestly associated with PITX2c expression located in the introns of the ENPEP gene, ∼54 kb proximal to PITX2. PITX2c expression in human adult left atrial appendages is not associated with the chromosome 4q25 AF risk SNPs; thus, the mechanism by which these SNPs are associated with AF remains enigmatic.

Non-Viral Generation of Neural Precursor-like Cells from Adult Human Fibroblasts

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Maucksch C

2012-01-01

Full Text Available Recent studies have reported direct reprogramming of human fibroblasts to mature neurons by the introduction of defined neural genes. This technology has potential use in the areas of neurological disease modeling and drug development. However, use of induced neurons for large-scale drug screening and cell-based replacement strategies is limited due to their inability to expand once reprogrammed. We propose it would be more desirable to induce expandable neural precursor cells directly from human fibroblasts. To date several pluripotent and neural transcription factors have been shown to be capable of converting mouse fibroblasts to neural stem/precursor-like cells when delivered by viral vectors. Here we extend these findings and demonstrate that transient ectopic insertion of the transcription factors SOX2 and PAX6 to adult human fibroblasts through use of non-viral plasmid transfection or protein transduction allows the generation of induced neural precursor (iNP colonies expressing a range of neural stem and pro-neural genes. Upon differentiation, iNP cells give rise to neurons exhibiting typical neuronal morphologies and expressing multiple neuronal markers including tyrosine hydroxylase and GAD65/67. Importantly, iNP-derived neurons demonstrate electrophysiological properties of functionally mature neurons with the capacity to generate action potentials. In addition, iNP cells are capable of differentiating into glial fibrillary acidic protein (GFAP-expressing astrocytes. This study represents a novel virus-free approach for direct reprogramming of human fibroblasts to a neural precursor fate.

Enhanced astrocytic nitric oxide production and neuronal modifications in the neocortex of a NOS2 mutant mouse.

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Yossi Buskila

Full Text Available BACKGROUND: It has been well accepted that glial cells in the central nervous system (CNS produce nitric oxide (NO through the induction of a nitric oxide synthase isoform (NOS2 only in response to various insults. Recently we described rapid astroglial, NOS2-dependent, NO production in the neocortex of healthy mice on a time scale relevant to neuronal activity. To explore a possible role for astroglial NOS2 in normal brain function we investigated a NOS2 knockout mouse (B6;129P2-Nos2(tm1Lau/J, Jackson Laboratory. Previous studies of this mouse strain revealed mainly altered immune responses, but no compensatory pathways and no CNS abnormalities have been reported. METHODOLOGY/PRINCIPAL FINDINGS: To our surprise, using NO imaging in brain slices in combination with biochemical methods we uncovered robust NO production by neocortical astrocytes of the NOS2 mutant. These findings indicate the existence of an alternative pathway that increases basal NOS activity. In addition, the astroglial mutation instigated modifications of neuronal attributes, shown by changes in the membrane properties of pyramidal neurons, and revealed in distinct behavioral abnormalities characterized by an increase in stress-related parameters. CONCLUSIONS/SIGNIFICANCE: The results strongly indicate the involvement of astrocytic-derived NO in modifying the activity of neuronal networks. In addition, the findings corroborate data linking NO signaling with stress-related behavior, and highlight the potential use of this genetic model for studies of stress-susceptibility. Lastly, our results beg re-examination of previous studies that used this mouse strain to examine the pathophysiology of brain insults, assuming lack of astrocytic nitrosative reaction.

High adult mortality among Hiwi hunter-gatherers: implications for human evolution.

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Hill, Kim; Hurtado, A M; Walker, R S

2007-04-01

Extant apes experience early sexual maturity and short life spans relative to modern humans. Both of these traits and others are linked by life-history theory to mortality rates experienced at different ages by our hominin ancestors. However, currently there is a great deal of debate concerning hominin mortality profiles at different periods of evolutionary history. Observed rates and causes of mortality in modern hunter-gatherers may provide information about Upper Paleolithic mortality that can be compared to indirect evidence from the fossil record, yet little is published about causes and rates of mortality in foraging societies around the world. To our knowledge, interview-based life tables for recent hunter-gatherers are published for only four societies (Ache, Agta, Hadza, and Ju/'hoansi). Here, we present mortality data for a fifth group, the Hiwi hunter-gatherers of Venezuela. The results show comparatively high death rates among the Hiwi and highlight differences in mortality rates among hunter-gatherer societies. The high levels of conspecific violence and adult mortality in the Hiwi may better represent Paleolithic human demographics than do the lower, disease-based death rates reported in the most frequently cited forager studies.

Developmentally inspired programming of adult human mesenchymal stromal cells toward stable chondrogenesis.

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Occhetta, Paola; Pigeot, Sebastien; Rasponi, Marco; Dasen, Boris; Mehrkens, Arne; Ullrich, Thomas; Kramer, Ina; Guth-Gundel, Sabine; Barbero, Andrea; Martin, Ivan

2018-05-01

It is generally accepted that adult human bone marrow-derived mesenchymal stromal cells (hMSCs) are default committed toward osteogenesis. Even when induced to chondrogenesis, hMSCs typically form hypertrophic cartilage that undergoes endochondral ossification. Because embryonic mesenchyme is obviously competent to generate phenotypically stable cartilage, it is questioned whether there is a correspondence between mesenchymal progenitor compartments during development and in adulthood. Here we tested whether forcing specific early events of articular cartilage development can program hMSC fate toward stable chondrogenesis. Inspired by recent findings that spatial restriction of bone morphogenetic protein (BMP) signaling guides embryonic progenitors toward articular cartilage formation, we hypothesized that selective inhibition of BMP drives the phenotypic stability of hMSC-derived chondrocytes. Two BMP type I receptor-biased kinase inhibitors were screened in a microfluidic platform for their time- and dose-dependent effect on hMSC chondrogenesis. The different receptor selectivity profile of tested compounds allowed demonstration that transient blockade of both ALK2 and ALK3 receptors, while permissive to hMSC cartilage formation, is necessary and sufficient to maintain a stable chondrocyte phenotype. Remarkably, even upon compound removal, hMSCs were no longer competent to undergo hypertrophy in vitro and endochondral ossification in vivo, indicating the onset of a constitutive change. Our findings demonstrate that adult hMSCs effectively share properties of embryonic mesenchyme in the formation of transient but also of stable cartilage. This opens potential pharmacological strategies to articular cartilage regeneration and more broadly indicates the relevance of developmentally inspired protocols to control the fate of adult progenitor cell systems.

Over-expression of hNGF in adult human olfactory bulb neural stem cells promotes cell growth and oligodendrocytic differentiation

NARCIS (Netherlands)

H.E.S. Marei (Hany); A. Althani (Asmaa); N. Afifi (Nahla); A. Abd-Elmaksoud (Ahmed); C. Bernardini (Camilla); F. Michetti (Fabrizio); M. Barba (Marta); M. Pescatori (Mario); G. Maira (Giulio); E. Paldino (Emanuela); L. Manni (Luigi); P. Casalbore (Patrizia); C. Cenciarelli (Carlo)

2013-01-01

textabstractThe adult human olfactory bulb neural stem/progenitor cells (OBNC/PC) are promising candidate for cell-based therapy for traumatic and neurodegenerative insults. Exogenous application of NGF was suggested as a promising therapeutic strategy for traumatic and neurodegenerative diseases,

Physical Exercise Habits Correlate with Gray Matter Volume of the Hippocampus in Healthy Adult Humans

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Killgore, William D. S.; Olson, Elizabeth A.; Weber, Mareen

2013-12-01

Physical activity facilitates neurogenesis of dentate cells in the rodent hippocampus, a brain region critical for memory formation and spatial representation. Recent findings in humans also suggest that aerobic exercise can lead to increased hippocampal volume and enhanced cognitive functioning in children and elderly adults. However, the association between physical activity and hippocampal volume during the period from early adulthood through middle age has not been effectively explored. Here, we correlated the number of minutes of self-reported exercise per week with gray matter volume of the hippocampus using voxel-based morphometry (VBM) in 61 healthy adults ranging from 18 to 45 years of age. After controlling for age, gender, and total brain volume, total minutes of weekly exercise correlated significantly with volume of the right hippocampus. Findings highlight the relationship between regular physical exercise and brain structure during early to middle adulthood.

Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature

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Qing-quan Li

2015-01-01

Full Text Available The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial fibrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identified using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromodeoxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial fibrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our findings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells.

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Ramachandran, Sarada Devi; Schirmer, Katharina; Münst, Bernhard; Heinz, Stefan; Ghafoory, Shahrouz; Wölfl, Stefan; Simon-Keller, Katja; Marx, Alexander; Øie, Cristina Ionica; Ebert, Matthias P; Walles, Heike; Braspenning, Joris; Breitkopf-Heinlein, Katja

2015-01-01

In this study we used differentiated adult human upcyte® cells for the in vitro generation of liver organoids. Upcyte® cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte® process). Proliferating upcyte® cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte® cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel™, they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions.

Estimated Human and Economic Burden of Four Major Adult Vaccine-Preventable Diseases in the United States, 2013.

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McLaughlin, John M; McGinnis, Justin J; Tan, Litjen; Mercatante, Annette; Fortuna, Joseph

2015-08-01

Low uptake of routinely recommended adult immunizations is a public health concern. Using data from the peer-reviewed literature, government disease-surveillance programs, and the US Census, we developed a customizable model to estimate human and economic burden caused by four major adult vaccine-preventable diseases (VPD) in 2013 in the United States, and for each US state individually. To estimate the number of cases for each adult VPD for a given population, we multiplied age-specific incidence rates obtained from the literature by age-specific 2013 Census population data. We then multiplied the estimated number of cases for a given population by age-specific, estimated medical and indirect (non-medical) costs per case. Adult VPDs examined were: (1) influenza, (2) pneumococcal disease (both invasive disease and pneumonia), (3) herpes zoster (shingles), and (4) pertussis (whooping cough). Sensitivity analyses simulated the impact of various epidemiological scenarios on the total estimated economic burden. Estimated US annual cost for the four adult VPDs was $26.5 billion (B) among adults aged 50 years and older, $15.3B (58 %) of which was attributable to those 65 and older. Among adults 50 and older, influenza, pneumococcal disease, herpes zoster, and pertussis made up $16.0B (60 %), $5.1B (19 %), $5.0B (19 %), and $0.4B (2 %) of the cost, respectively. Among those 65 and older, they made up $8.3B (54 %), $3.8B (25 %), $3.0B (20 %), and 0.2B (1 %) of the cost, respectively. Most (80-85 %) pneumococcal costs stemmed from nonbacteremic pneumococcal pneumonia (NPP). Cost attributable to adult VPD in the United States is substantial. Broadening adult immunization efforts beyond influenza only may help reduce the economic burden of adult VPD, and a pneumococcal vaccination effort, primarily focused on reducing NPP, may constitute a logical starting place. Sensitivity analyses revealed that a pandemic influenza season or change in size of the US elderly population

ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs.

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Lee, Michelle H; Goralczyk, Anna G; Kriszt, Rókus; Ang, Xiu Min; Badowski, Cedric; Li, Ying; Summers, Scott A; Toh, Sue-Anne; Yassin, M Shabeer; Shabbir, Asim; Sheppard, Allan; Raghunath, Michael

2016-02-17

Key to realizing the diagnostic and therapeutic potential of human brown/brite adipocytes is the identification of a renewable, easily accessible and safe tissue source of progenitor cells, and an efficacious in vitro differentiation protocol. We show that macromolecular crowding (MMC) facilitates brown adipocyte differentiation in adult human bone marrow mesenchymal stem cells (bmMSCs), as evidenced by substantially upregulating uncoupling protein 1 (UCP1) and uncoupled respiration. Moreover, MMC also induced 'browning' in bmMSC-derived white adipocytes. Mechanistically, MMC creates a 3D extracellular matrix architecture enshrouding maturing adipocytes in a collagen IV cocoon that is engaged by paxillin-positive focal adhesions also at the apical side of cells, without contact to the stiff support structure. This leads to an enhanced matrix-cell signaling, reflected by increased phosphorylation of ATF2, a key transcription factor in UCP1 regulation. Thus, tuning the dimensionality of the microenvironment in vitro can unlock a strong brown potential dormant in bone marrow.

Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults

Science.gov (United States)

Chambers, Edward S; Viardot, Alexander; Psichas, Arianna; Morrison, Douglas J; Murphy, Kevin G; Zac-Varghese, Sagen E K; MacDougall, Kenneth; Preston, Tom; Tedford, Catriona; Finlayson, Graham S; Blundell, John E; Bell, Jimmy D; Thomas, E Louise; Mt-Isa, Shahrul; Ashby, Deborah; Gibson, Glen R; Kolida, Sofia; Dhillo, Waljit S; Bloom, Stephen R; Morley, Wayne; Clegg, Stuart; Frost, Gary

2015-01-01

Objective The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults. Design To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults. Results Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group. Conclusions These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans. Trial registration number NCT00750438. PMID:25500202

Characterization of neuronal intrinsic properties and synaptic transmission in layer I of anterior cingulate cortex from adult mice

Directory of Open Access Journals (Sweden)

Li Xiang-Yao

2012-07-01

Full Text Available Abstract The neurons in neocortex layer I (LI provide inhibition to the cortical networks. Despite increasing use of mice for the study of brain functions, few studies were reported about mouse LI neurons. In the present study, we characterized intrinsic properties of LI neurons of the anterior cingulate cortex (ACC, a key cortical area for sensory and cognitive functions, by using whole-cell patch clamp recording approach. Seventy one neurons in LI and 12 pyramidal neurons in LII/III were recorded. Although all of the LI neurons expressed continuous adapting firing characteristics, the unsupervised clustering results revealed five groups in the ACC, including: Spontaneous firing neurons; Delay-sAHP neurons, Delay-fAHP neurons, and two groups of neurons with ADP, named ADP1 and ADP2, respectively. Using pharmacological approaches, we found that LI neurons received both excitatory (mediated by AMPA, kainate and NMDA receptors, and inhibitory inputs (which were mediated by GABAA receptors. Our studies provide the first report characterizing the electrophysiological properties of neurons in LI of the ACC from adult mice.

Adult Human Pancreatic Islet Beta-Cells Display Limited Turnover and Long Lifespan as Determined by In-Vivo Thymidine Analog Incorporation and Radiocarbon Dating

Energy Technology Data Exchange (ETDEWEB)

Perl, S; Kushner, J A; Buchholz, B A; Meeker, A K; Stein, G M; Hsieh, M; Kirby, M; Pechhold, S; Liu, E H; Harlan, D M; Tisdale, J F

2010-03-15

Diabetes mellitus results from an absolute or relative deficiency of insulin producing pancreatic beta-cells. The adult human beta-cell's turnover rate remains unknown. We employed novel techniques to examine adult human islet beta-cell turnover and longevity in vivo. Subjects enrolled in NIH clinical trials received thymidine analogues [iododeoxyuridine (IdU) or bromodeoxyuridine (BrdU)] 8-days to 4-years prior to death. Archival autopsy samples from ten patients (aged 17-74 years) were employed to assess beta-cell turnover by scoring nuclear analog labeling within insulin staining cells. Human adult beta-cell longevity was determined by estimating the cells genomic DNA integration of atmospheric carbon-14 ({sup 14}C). DNA was purified from pancreatic islets isolated from cadaveric donors; whole islet prep DNA was obtained from a 15 year old donor, and purified beta-cell DNA was obtained from two donors (age 48 and 80 years). {sup 14}C levels were then determined using accelerator mass spectrometry (AMS). Cellular 'birth date' was determined by comparing the subject's DNA {sup 14}C content relative to a well-established {sup 14}C atmospheric prevalence curve. In the two subjects less than age 20 years, 1-2% of the beta-cell nuclei co-stained for BrdU/IdU. No beta-cell nuclei co-stained in the eight patients more than 30 years old. Consistent with the BrdU/IdU turnover data, beta-cell DNA {sup 14}C content indicated the cells 'birth date' occurred within the subject's first 30 years of life. Under typical circumstances, adult human beta-cells and their cellular precursors are established by young adulthood.

Rapid consolidation of new knowledge in adulthood via fast mapping.

Science.gov (United States)

Coutanche, Marc N; Thompson-Schill, Sharon L

2015-09-01

Rapid word learning, where words are 'fast mapped' onto new concepts, may help build vocabulary during childhood. Recent evidence has suggested that fast mapping might help to rapidly integrate information into memory networks of the adult neocortex. The neural basis for this learning by fast mapping determines key properties of the learned information. Copyright © 2015 Elsevier Ltd. All rights reserved.

The saucor, a new stereological tool for analysing the spatial distributions of cells, exemplified by human neocortical neurons and glial cells

DEFF Research Database (Denmark)

Stark, Anette K.; Gundersen, Hans Jørgen Gottlieb; Gardi, Jonathan Eyal

The three dimensional spatial arrangement of particles or cells, for example glial cells, with respect to other particles or cells, for example neurons, can be characterized by the radial number density function, which expresses the number density of so called “secondary” particles as a function....... Estimation formulae based on the Horvitz-Thompson theorem are derived for both IUR and VUR designs. The method is illustrated with an example where the radial number density of neurons and glial cells around neurons in the human neocortex is estimated using thick vertical sections for light microscopy....... The results indicate that the glial cells are clustered around the neurons and the neurons have a tendency towards repulsion from each other....

Healthy young adults implement distinctive avoidance strategies while walking and circumventing virtual human vs. non-human obstacles in a virtual environment.

Science.gov (United States)

Souza Silva, Wagner; Aravind, Gayatri; Sangani, Samir; Lamontagne, Anouk

2018-03-01

This study examines how three types of obstacles (cylinder, virtual human and virtual human with footstep sounds) affect circumvention strategies of healthy young adults. Sixteen participants aged 25.2 ± 2.5 years (mean ± 1SD) were tested while walking overground and viewing a virtual room through a helmet mounted display. As participants walked towards a stationary target in the far space, they avoided an obstacle (cylinder or virtual human) approaching either from the right (+40°), left (-40°) or head-on (0°). Obstacle avoidance strategies were characterized using the position and orientation of the head. Repeated mixed model analysis showed smaller minimal distances (p = 0.007) while avoiding virtual humans as compared to cylinders. Footstep sounds added to virtual humans did not modify (p = 0.2) minimal distances compared to when no sound was provided. Onset times of avoidance strategies were similar across conditions (p = 0.06). Results indicate that the nature of the obstacle (human-like vs. non-human object) matters and can modify avoidance strategies. Smaller obstacle clearances in response to virtual humans may reflect the use of a less conservative avoidance strategy, due to a resemblance of obstacles to pedestrians and a recall of strategies used in daily locomotion. The lack of influence of footstep sounds supports the fact that obstacle avoidance primarily relies on visual cues and the principle of 'inverse effectiveness' whereby multisensory neurons' response to multimodal stimuli becomes weaker when the unimodal sensory stimulus (vision) is strong. Present findings should be taken into consideration to optimize the ecological validity of VR-based obstacle avoidance paradigms used in research and rehabilitation. Copyright © 2018 Elsevier B.V. All rights reserved.

Physiological Parameters Database for Older Adults

Data.gov (United States)

U.S. Environmental Protection Agency — The Physiological Parameters Database for Older Adults is available for download and contains physiological parameters values for healthy older human adults (age 60...

Current Cigarette Smoking Among Adults Infographic

Data.gov (United States)

U.S. Department of Health & Human Services — Explore the Current Cigarette Smoking Among Adults Infographic which outlines key facts related to current smoking among adults. For accessibility issues contact...

From mice to men: the evolution of the large, complex human brain

Indian Academy of Sciences (India)

2004-12-15

Dec 15, 2004 ... https://www.ias.ac.in/article/fulltext/jbsc/030/02/0155-0165. Keywords. Galagos; neocortex; primates; somatosensory; vision. Author Affiliations. Jon H Kaas1. Department of Psychology, Vanderbilt University, 301 Wilson Hall, 111, 21st Ave. S, Nashville, TN 37240, USA. Dates. Early published: 15 December ...

From mice to men: the evolution of the large, complex human brain

Indian Academy of Sciences (India)

2004-12-15

Dec 15, 2004 ... http://www.ias.ac.in/article/fulltext/jbsc/030/02/0155-0165. Keywords. Galagos; neocortex; primates; somatosensory; vision. Author Affiliations. Jon H Kaas1. Department of Psychology, Vanderbilt University, 301 Wilson Hall, 111, 21st Ave. S, Nashville, TN 37240, USA. Dates. Early published: 15 December ...

Conversion of adult human peripheral blood mononuclear cells into induced neural stem cell by using episomal vectors

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Xihe Tang

2016-03-01

Full Text Available Human neural stem cells (NSCs hold great promise for research and therapy in neural diseases. Many studies have shown direct induction of NSCs from human fibroblasts, which require an invasive skin biopsy and a prolonged period of expansion in cell culture prior to use. Peripheral blood (PB is routinely used in medical diagnoses, and represents a noninvasive and easily accessible source of cells. Here we show direct derivation of NSCs from adult human PB mononuclear cells (PB-MNCs by employing episomal vectors for transgene delivery. These induced NSCs (iNSCs can expand more than 60 passages, can exhibit NSC morphology, gene expression, differentiation potential, and self-renewing capability and can give rise to multiple functional neural subtypes and glial cells in vitro. Furthermore, the iNSCs carry a specific regional identity and have electrophysiological activity upon differentiation. Our findings provide an easily accessible approach for generating human iNSCs which will facilitate disease modeling, drug screening, and possibly regenerative medicine.

Directly Converted Human Fibroblasts Mature to Neurons and Show Long-Term Survival in Adult Rodent Hippocampus

Directory of Open Access Journals (Sweden)

Natalia Avaliani

2017-01-01

Full Text Available Direct conversion of human somatic cells to induced neurons (iNs, using lineage-specific transcription factors has opened new opportunities for cell therapy in a number of neurological diseases, including epilepsy. In most severe cases of epilepsy, seizures often originate in the hippocampus, where populations of inhibitory interneurons degenerate. Thus, iNs could be of potential use to replace these lost interneurons. It is not known, however, if iNs survive and maintain functional neuronal properties for prolonged time periods in in vivo. We transplanted human fibroblast-derived iNs into the adult rat hippocampus and observed a progressive morphological differentiation, with more developed dendritic arborisation at six months as compared to one month. This was accompanied by mature electrophysiological properties and fast high amplitude action potentials at six months after transplantation. This proof-of-principle study suggests that human iNs can be developed as a candidate source for cell replacement therapy in temporal lobe epilepsy.

Human parvovirus B19-induced aplastic crisis in an adult patient with hereditary spherocytosis: a case report and review of the literature.

Science.gov (United States)

Kobayashi, Yujin; Hatta, Yoshihiro; Ishiwatari, Yusaku; Kanno, Hitoshi; Takei, Masami

2014-03-11

Although there are several case reports of human parvovirus B19 infection in patients with hereditary spherocytosis, no systematic reviews of adult patients with hereditary spherocytosis with human parvovirus B19 infection have been published as clinical case reports. In this study, we report a case of aplastic crisis due to human parvovirus B19 infection in an adult patient with hereditary spherocytosis. A 33-year-old woman with hereditary spherocytosis and gallstones was admitted because of rapid progress in marked anemia and fever. Although empiric antibiotic therapy was prescribed, her clinical symptoms and liver function test worsened. Because the anti-human parvovirus B19 antibody and deoxyribonucleic acid levels assessed by polymerase chain reaction were positive, the patient was diagnosed with aplastic crisis due to the human parvovirus B19 infection. We collected and reviewed several case reports of patients with hereditary spherocytosis aged > 18 years with human parvovirus B19 infection between 1984 and 2010. A total of 19 reports with 22 cases [median age, 28 years (range, 18-43 range); male: female ratio, 6:16], including the present case were identified. The male-to-female ratio of 6:16 implied that younger females were predominantly affected. Although fever and abdominal symptoms were common initial symptoms, liver dysfunction or skin eruptions were less commonly documented. Anti-human parvovirus B19 antibody or deoxyribonucleic acid levels assessed by polymerase chain reaction was commonly used to diagnose human parvovirus B19 infection and may be useful to distinguish human parvovirus B19 infection from other abdominal infection in patients with hereditary spherocytosis.

Skeletal 212Pb retention following 224Ra injection: extrapolation of animal data to adult humans

International Nuclear Information System (INIS)

Schlenker, R.A.

1988-01-01

Two methods of interspecies extrapolation, one based on a correlation of skeletal 212 Pb/ 224 Ra with body weight, the other based on the mechanistic relationship between skeletal 212 Pb/ 224 Ra and reciprocal bone surface-to-volume ratio, lead to the conclusion that the retention of 212 Pb in the adult human skeleton is approximately complete a few days after injection. The correlation-based method gives most probable values for 212 Pb/ 224 Ra of 1.0 and 1.1 at 2 d and 7 d after injection, compared with values of 1.05 and 1.27 expected at these same times if the retention of 212 Pb were complete from the time of injection and if no 212 Pb were in the injection solution. The range of values corresponding to one geometric standard error on either side of the most probable value is 0.87 to 1.21 at 2 d post-injection. With the method based on the reciprocal bone surface-to-volume ratio, the best estimate of 212 Pb/ 224 Ra at 2 d after injection is 0.88, equal to the value observed in young adult beagles. An alternative interpretation of the results of this latter method leads to the conclusion that retention is complete, with 212 Pb/ 224 Ra equal to 1.0 for a 212 Pb-free injection solution and 1.1 for a solution containing 212 Pb in secular equilibrium with 224 Ra. This work, which uses 224 Ra daughter product retention data from mice, rats and dogs following 224Ra injection, provides a scientific foundation for retention assumptions made in the calculation of mean skeletal dose for adult humans. There now appear to be few uncertainties in these latter dose values, stemming from inaccurate retention assumptions; but substantial uncertainties remain in the mean skeletal dose values for juveniles and in the endosteal tissue doses regardless of age

Expression profile of Lgi1 gene in mouse brain during development.

Science.gov (United States)

Ribeiro, Patrícia A O; Sbragia, Lourenço; Gilioli, Rovilson; Langone, Francesco; Conte, Fábio F; Lopes-Cendes, Iscia

2008-07-01

Mutations in LGI1 were described in patients with autosomal dominant partial epilepsy with auditory features (ADPEAF), and recent clinical findings have implicated LGI1 in human brain development. However, the precise role of LGI1 in epileptogenesis remains largely unknown. The objective of this study was to determine the expression pattern of Lgi1 in mice brain during development and in adult animals. Real-time polymerase chain reaction (PCR) quantification and Western blot experiments showed a relative low expression during intrauterine stages, increasing until adulthood. In addition, we did not find significant differences between left and right hemispheres. The hippocampus presented higher levels of Lgi1 expression when compared to the neocortex and the cerebellum of adult animals; however, these results did not reach statistical significance. This study was the first to determine a specific profile of Lgi1 gene expression during central nervous system development, which suggests a possible inhibitory function in latter stages of development. In addition, we did not find differences in hemispheric expression that could explain the predominance of left-sided abnormalities in patients with ADPEAF.

Isolation and characterization of adult human liver progenitors from ischemic liver tissue derived from therapeutic hepatectomies.

Science.gov (United States)

Stachelscheid, Harald; Urbaniak, Thomas; Ring, Alexander; Spengler, Berlind; Gerlach, Jörg C; Zeilinger, Katrin

2009-07-01

Recent evidence suggests that progenitor cells in adult tissues and embryonic stem cells share a high resistance to hypoxia and ischemic stress. To study the ischemic resistance of adult liver progenitors, we characterized remaining viable cells in human liver tissue after cold ischemic treatment for 24-168 h, applied to the tissue before cell isolation. In vitro cultures of isolated cells showed a rapid decline of the number of different cell types with increasing ischemia length. After all ischemic periods, liver progenitor-like cells could be observed. The comparably small cells exhibited a low cytoplasm-to-nucleus ratio, formed densely packed colonies, and showed a hepatobiliary marker profile. The cells expressed epithelial cell adhesion molecule, epithelial-specific (CK8/18) and biliary-specific (CK7/19) cytokeratins, albumin, alpha-1-antitrypsin, cytochrome-P450 enzymes, as well as weak levels of hepatocyte nuclear factor-4 and gamma-glutamyl transferase, but not alpha-fetoprotein or Thy-1. In vitro survival and expansion was facilitated by coculture with mouse embryonic fibroblasts. Hepatic progenitor-like cells exhibit a high resistance to ischemic stress and can be isolated from human liver tissue after up to 7 days of ischemia. Ischemic liver tissue from various sources, thought to be unsuitable for cell isolation, may be considered as a prospective source of hepatic progenitor cells.

The saucor, a new stereological tool for analysing the spatial distributions of cells, exemplified by human neocortical neurons and glial cells

DEFF Research Database (Denmark)

Stark, Anette K; Gundersen, Hans Jørgen Gottlieb; Gardi, Jonathan Eyal

2011-01-01

The 3D spatial arrangement of particles or cells, for example glial cells, with respect to other particles or cells, for example neurons, can be characterized by the radial number density function, which expresses the number density of so-called ‘secondary’ particles as a function of their distance...... formulae based on the Horvitz–Thompson theorem are derived for both isotropic uniform random and vertical uniform random designs. The method is illustrated with an example where the radial number density of neurons and glial cells around neurons in the human neocortex is estimated using thick vertical...... sections for light microscopy. The results indicate that the glial cells are clustered around the neurons and the neurons have a tendency towards repulsion from each other....

Growth Hormone Safety Workshop Position Paper: a critical appraisal of recombinant human growth hormone therapy in children and adults

DEFF Research Database (Denmark)

Allen, David B; Backeljauw, Philippe; Bidlingmaier, Martin

2015-01-01

Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statem...... (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.......Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however......, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard...

The human homeobox genes MSX-1, MSX-2, and MOX-1 are differentially expressed in the dermis and epidermis in fetal and adult skin.

Science.gov (United States)

Stelnicki, E J; Kömüves, L G; Holmes, D; Clavin, W; Harrison, M R; Adzick, N S; Largman, C

1997-10-01

In order to identify homeobox genes which may regulate skin development and possibly mediate scarless fetal wound healing we have screened amplified human fetal skin cDNAs by polymerase chain reaction (PCR) using degenerate oligonucleotide primers designed against highly conserved regions within the homeobox. We identified three non-HOX homeobox genes, MSX-1, MSX-2, and MOX-1, which were differentially expressed in fetal and adult human skin. MSX-1 and MSX-2 were detected in the epidermis, hair follicles, and fibroblasts of the developing fetal skin by in situ hybridization. In contrast, MSX-1 and MSX-2 expression in adult skin was confined to epithelially derived structures. Immunohistochemical analysis of these two genes suggested that their respective homeoproteins may be differentially regulated. While Msx-1 was detected in the cell nucleus of both fetal and adult skin; Msx-2 was detected as a diffuse cytoplasmic signal in fetal epidermis and portions of the hair follicle and dermis, but was localized to the nucleus in adult epidermis. MOX-1 was expressed in a pattern similar to MSX early in gestation but then was restricted exclusively to follicular cells in the innermost layer of the outer root sheath by 21 weeks of development. Furthermore, MOX-1 expression was completely absent in adult cutaneous tissue. These data imply that each of these homeobox genes plays a specific role in skin development.

Multiple embryonic origins of nitric oxide synthase-expressing GABAergic neurons of the neocortex

Directory of Open Access Journals (Sweden)

Lorenza eMagno

2012-09-01

Full Text Available Cortical GABAergic interneurons in rodents originate in three subcortical regions: the medial ganglionic eminence (MGE, the lateral/caudal ganglionic eminence (LGE/CGE and the preoptic area (POA. Each of these neuroepithelial precursor domains contributes different interneuron subtypes to the cortex. nNOS-expressing neurons represent a heterogenous population of cortical interneurons. We examined the development of these cells in the mouse embryonic cortex and their abundance and distribution in adult animals. Using genetic lineage tracing in transgenic mice we find that nNOS type I cells originate only in the MGE whereas type II cells have a triple origin in the MGE, LGE/CGE and POA. The two populations are born at different times during development, occupy different layers in the adult cortex and have distinct neurochemical profiles. nNOS neurons are more numerous in the adult cortex than previously reported and constitute a significant proportion of the cortical interneuron population. Our data suggest that the heterogeneity of nNOS neurons in the cortex can be attributed to their multiple embryonic origins which likely impose distinct genetic specification programs.

Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms

DEFF Research Database (Denmark)

Svingen, T; Jørgensen, Anne; Rajpert-De Meyts, E

2014-01-01

to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers......, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis...... and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further...

Altered neuronal architecture and plasticity in the visual cortex of adult MMP-3 deficient mice

OpenAIRE

Aerts, Jeroen; Nys, Julie; Moons, Lieve; Hu, Tjing-Tjing; Arckens, Lut

2015-01-01

Matrix metalloproteinases (MMPs) are Zn2+ dependent endopeptidases considered to be essential for normal brain development and neuroplasticity by modulating extracellular matrix proteins, receptors, adhesion molecules, growth factors and cytoskeletal proteins. Specifically MMP-3 has recently been implicated in synaptic plasticity, hippocampus-dependent learning and neuronal development and migration in the cerebellum. However, the function(s) of this enzyme in the neocortex is understudied. T...

Intermittent Hypoxia Causes Inflammation and Injury to Human Adult Cardiac Myocytes.

Science.gov (United States)

Wu, Jing; Stefaniak, Joanna; Hafner, Christina; Schramel, Johannes Peter; Kaun, Christoph; Wojta, Johann; Ullrich, Roman; Tretter, Verena Eva; Markstaller, Klaus; Klein, Klaus Ulrich

2016-02-01

Intermittent hypoxia may occur in a number of clinical scenarios, including interruption of myocardial blood flow or breathing disorders such as obstructive sleep apnea. Although intermittent hypoxia has been linked to cardiovascular and cerebrovascular disease, the effect of intermittent hypoxia on the human heart is not fully understood. Therefore, in the present study, we compared the cellular responses of cultured human adult cardiac myocytes (HACMs) exposed to intermittent hypoxia and different conditions of continuous hypoxia and normoxia. HACMs were exposed to intermittent hypoxia (0%-21% O2), constant mild hypoxia (10% O2), constant severe hypoxia (0% O2), or constant normoxia (21% O2), using a novel cell culture bioreactor with gas-permeable membranes. Cell proliferation, lactate dehydrogenase release, vascular endothelial growth factor release, and cytokine (interleukin [IL] and macrophage migration inhibitory factor) release were assessed at baseline and after 8, 24, and 72 hours of exposure. A signal transduction pathway finder array was performed to determine the changes in gene expression. In comparison with constant normoxia and constant mild hypoxia, intermittent hypoxia induced earlier and greater inflammatory response and extent of cell injury as evidenced by lower cell numbers and higher lactate dehydrogenase, vascular endothelial growth factor, and proinflammatory cytokine (IL-1β, IL-6, IL-8, and macrophage migration inhibitory factor) release. Constant severe hypoxia showed more detrimental effects on HACMs at later time points. Pathway analysis demonstrated that intermittent hypoxia primarily altered gene expression in oxidative stress, Wnt, Notch, and hypoxia pathways. Intermittent and constant severe hypoxia, but not constant mild hypoxia or normoxia, induced inflammation and cell injury in HACMs. Cell injury occurred earliest and was greatest after intermittent hypoxia exposure. Our in vitro findings suggest that intermittent hypoxia

InGaP - CREATE portal | LSDB Archive [Life Science Database Archive metadata

Lifescience Database Archive (English)

Full Text Available : Fixed mouse brain sections were fluorescent-labeled and observed by confocal laser scanning microscope usi...ted GFP-fusion KIAA/mKIAA in HEK293 cells were observed by fluorescent microscope...ope (neocortex 1) Observation by Confocal laser scanning microscope (neocortex 1) C...onfocal laser scanning microscope (neocortex 2) Observation by Confocal laser scanning microscope (neocortex... 2) Confocal laser scanning microscope (hippocampus) Observation by Confocal laser scanning microscope

Strengths and Satisfaction across the Adult Lifespan

Science.gov (United States)

Isaacowitz, Derek M.; Vaillant, George E.; Seligman, Martin E. P.

2003-01-01

Positive psychology has recently developed a classification of human strengths (Peterson & Seligman, in press). We aimed to evaluate these strengths by investigating the strengths and life satisfaction in three adult samples recruited from the community (young adult, middle-aged, and older adult), as well as in the surviving men of the Grant study…

NOHSS Adult Indicators

Data.gov (United States)

U.S. Department of Health & Human Services — 2012-2014 (even years). Data from BRFSS for indicators of adult oral health for even years from 2012 through 2014. National estimates are represented by the median...

A structurally detailed finite element human head model for simulation of transcranial magnetic stimulation.

Science.gov (United States)

Chen, Ming; Mogul, David Jeffery

2009-04-30

Computational studies of the head utilizing finite element models (FEMs) have been used to investigate a wide variety of brain-electromagnetic (EM) field interaction phenomena including magnetic stimulation of the head using transcranial magnetic stimulation (TMS), direct electric stimulation of the brain for electroconvulsive therapy, and electroencephalography source localization. However, no human head model of sufficient complexity for studying the biophysics under these circumstances has been developed which utilizes structures at both the regional and cellular levels and provides well-defined smooth boundaries between tissues of different conductivities and orientations. The main barrier for building such accurate head models is the complex modeling procedures that include 3D object reconstruction and optimized meshing. In this study, a structurally detailed finite element model of the human head was generated that includes details to the level of cerebral gyri and sulci by combining computed tomography and magnetic resonance images. Furthermore, cortical columns that contain conductive processes of pyramidal neurons traversing the neocortical layers were included in the head model thus providing structure at or near the cellular level. These refinements provide a much more realistic model to investigate the effects of TMS on brain electrophysiology in the neocortex.

A balanced view of the cerebrospinal fluid composition and functions: Focus on adult humans.

Science.gov (United States)

Spector, Reynold; Robert Snodgrass, S; Johanson, Conrad E

2015-11-01

In this review, a companion piece to our recent examination of choroid plexus (CP), the organ that secretes the cerebrospinal fluid (CSF), we focus on recent information in the context of reliable older data concerning the composition and functions of adult human CSF. To accomplish this, we define CSF, examine the methodology employed in studying the CSF focusing on ideal or near ideal experiments and discuss the pros and cons of several widely used analogical descriptions of the CSF including: the CSF as the "third circulation," the CSF as a "nourishing liquor," the similarities of the CSF/choroid plexus to the glomerular filtrate/kidney and finally the CSF circulation as part of the "glymphatic system." We also consider the close interrelationship between the CSF and extracellular space of brain through gap junctions and the paucity of data suggesting that the cerebral capillaries secrete a CSF-like fluid. Recently human CSF has been shown to be in dynamic flux with heart-beat, posture and especially respiration. Functionally, the CSF provides buoyancy, nourishment (e.g., vitamins) and endogenous waste product removal for the brain by bulk flow into the venous (arachnoid villi and nerve roots) and lymphatic (nasal) systems, and by carrier-mediated reabsorptive transport systems in CP. The CSF also presents many exogenous compounds to CP for metabolism or removal, indirectly cleansing the extracellular space of brain (e.g., of xenobiotics like penicillin). The CSF also carries hormones (e.g., leptin) from blood via CP or synthesized in CP (e.g., IGF-2) to the brain. In summary the CP/CSF, the third circulation, performs many functions comparable to the kidney including nourishing the brain and contributing to a stable internal milieu for the brain. These tasks are essential to normal adult brain functioning. Copyright © 2015. Published by Elsevier Inc.

Patient-specific FDG dosimetry for adult males, adult females, and very low birth weight infants

Science.gov (United States)

Niven, Erin

Fluorodeoxyglucose is the most commonly used radiopharmaceutical in Positron Emission Tomography, with applications in neurology, cardiology, and oncology. Despite its routine use worldwide, the radiation absorbed dose estimates from FDG have been based primarily on data obtained from two dogs studied in 1977 and 11 adults (most likely males) studied in 1982. In addition, the dose estimates calculated for FDG have been centered on the adult male, with little or no mention of variations in the dose estimates due to sex, age, height, weight, nationality, diet, or pathological condition. Through an extensive investigation into the Medical Internal Radiation Dose schema for calculating absorbed doses, I have developed a simple patient-specific equation; this equation incorporates the parameters necessary for alterations to the mathematical values of the human model to produce an estimate more representative of the individual under consideration. I have used this method to determine the range of absorbed doses to FDG from the collection of a large quantity of biological data obtained in adult males, adult females, and very low birth weight infants. Therefore, a more accurate quantification of the dose to humans from FDG has been completed. My results show that per unit administered activity, the absorbed dose from FDG is higher for infants compared to adults, and the dose for adult women is higher than for adult men. Given an injected activity of approximately 3.7 MBq kg-1, the doses for adult men, adult women, and full-term newborns would be on the order of 5.5, 7.1, and 2.8 mSv, respectively. These absorbed doses are comparable to the doses received from other nuclear medicine procedures.

Expression of nestin, mesothelin and epithelial membrane antigen (EMA) in developing and adult human meninges and meningiomas.

Science.gov (United States)

Petricevic, Josko; Forempoher, Gea; Ostojic, Ljerka; Mardesic-Brakus, Snjezana; Andjelinovic, Simun; Vukojevic, Katarina; Saraga-Babic, Mirna

2011-11-01

The spatial and temporal pattern of appearance of nestin, epithelial membrane antigen (EMA) and mesothelin proteins was immunohistochemically determined in the cells of normal developing and adult human meninges and meningiomas. Human meninges developed as two mesenchymal condensations in the head region. The simple squamous epithelium on the surface of leptomeninges developed during mesenchymal to epithelial transformation. Nestin appeared for the first time in week 7, EMA in week 8, while mesothelin appeared in week 22 of development. In the late fetal period and after birth, nestin expression decreased, whereas expression of EMA and mesothelin increased. EMA appeared in all surface epithelial cells and nodules, while mesothelin was found only in some of them. In adult meninges, all three proteins were predominantly localized in the surface epithelium and meningeal nodules. In meningothelial meningiomas (WHO grade I), EMA was detected in all tumor cells except in the endothelial cells, mesothelin characterized nests of tumor cells, while nestin was found predominantly in the walls of blood vessels. The distribution pattern of those proteins in normal meningeal and tumor cells indicates that nestin might characterize immature cells, while EMA and mesothelin appeared in maturing epithelial cells. Neoplastic transformation of these specific cell lineages contributes to the cell population in meningiomas. Copyright © 2010 Elsevier GmbH. All rights reserved.

Deficient retinoid-driven angiogenesis may contribute to failure of adult human lung regeneration in emphysema.

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Ng-Blichfeldt, John-Poul; Alçada, Joana; Montero, M Angeles; Dean, Charlotte H; Griesenbach, Uta; Griffiths, Mark J; Hind, Matthew

2017-06-01

Molecular pathways that regulate alveolar development and adult repair represent potential therapeutic targets for emphysema. Signalling via retinoic acid (RA), derived from vitamin A, is required for mammalian alveologenesis, and exogenous RA can induce alveolar regeneration in rodents. Little is known about RA signalling in the human lung and its potential role in lung disease. To examine regulation of human alveolar epithelial and endothelial repair by RA, and characterise RA signalling in human emphysema. The role of RA signalling in alveolar epithelial repair was investigated with a scratch assay using an alveolar cell line (A549) and primary human alveolar type 2 (AT2) cells from resected lung, and the role in angiogenesis using a tube formation assay with human lung microvascular endothelial cells (HLMVEC). Localisation of RA synthetic (RALDH-1) and degrading (cytochrome P450 subfamily 26 A1 (CYP26A1)) enzymes in human lung was determined by immunofluorescence. Regulation of RA pathway components was investigated in emphysematous and control human lung tissue by quantitative real-time PCR and Western analysis. RA stimulated HLMVEC angiogenesis in vitro; this was partially reproduced with a RAR-α agonist. RA induced mRNA expression of vascular endothelial growth factor A (VEGFA) and VEGFR2. RA did not modulate AT2 repair. CYP26A1 protein was identified in human lung microvasculature, whereas RALDH-1 partially co-localised with vimentin-positive fibroblasts. CYP26A1 mRNA and protein were increased in emphysema. RA regulates lung microvascular angiogenesis; the endothelium produces CYP26A1 which is increased in emphysema, possibly leading to reduced RA availability. These data highlight a role for RA in maintenance of the human pulmonary microvascular endothelium. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Bottom-Up versus Top-Down Induction of Sleep by Zolpidem Acting on Histaminergic and Neocortex Neurons

Science.gov (United States)

Uygun, David S.; Ye, Zhiwen; Zecharia, Anna Y.; Harding, Edward C.; Yu, Xiao; Yustos, Raquel; Vyssotski, Alexei L.; Brickley, Stephen G.

2016-01-01

Zolpidem, a GABAA receptor-positive modulator, is the gold-standard drug for treating insomnia. Zolpidem prolongs IPSCs to decrease sleep latency and increase sleep time, effects that depend on α2 and/or α3 subunit-containing receptors. Compared with natural NREM sleep, zolpidem also decreases the EEG power, an effect that depends on α1 subunit-containing receptors, and which may make zolpidem-induced sleep less optimal. In this paper, we investigate whether zolpidem needs to potentiate only particular GABAergic pathways to induce sleep without reducing EEG power. Mice with a knock-in F77I mutation in the GABAA receptor γ2 subunit gene are zolpidem-insensitive. Using these mice, GABAA receptors in the frontal motor neocortex and hypothalamic (tuberomammillary nucleus) histaminergic-neurons of γ2I77 mice were made selectively sensitive to zolpidem by genetically swapping the γ2I77 subunits with γ2F77 subunits. When histamine neurons were made selectively zolpidem-sensitive, systemic administration of zolpidem shortened sleep latency and increased sleep time. But in contrast to the effect of zolpidem on wild-type mice, the power in the EEG spectra of NREM sleep was not decreased, suggesting that these EEG power-reducing effects of zolpidem do not depend on reduced histamine release. Selective potentiation of GABAA receptors in the frontal cortex by systemic zolpidem administration also reduced sleep latency, but less so than for histamine neurons. These results could help with the design of new sedatives that induce a more natural sleep. SIGNIFICANCE STATEMENT Many people who find it hard to get to sleep take sedatives. Zolpidem (Ambien) is the most widely prescribed “sleeping pill.” It makes the inhibitory neurotransmitter GABA work better at its receptors throughout the brain. The sleep induced by zolpidem does not resemble natural sleep because it produces a lower power in the brain waves that occur while we are sleeping. We show using mouse genetics

Detection of human bocavirus from children and adults with acute respiratory tract illness in Guangzhou, southern China

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Liu Wen-Kuan

2011-12-01

Full Text Available Abstract Background Human bocavirus (HBoV is a newly discovered parvovirus associated with acute respiratory tract illness (ARTI and gastrointestinal illness. Our study is the first to analyze the characteristics of HBoV-positive samples from ARTI patients with a wide age distribution from Guangzhou, southern China. Methods Throat swabs (n=2811 were collected and analyzed from children and adults with ARTI over a 13-month period. The HBoV complete genome from a 60 year-old female patient isolate was also determined. Results HBoV DNA was detected in 65/2811 (2.3% samples, of which 61/1797 were from children (Mycoplasma pneumoniae had the highest frequency of 16.9% (11/65. Upper and lower respiratory tract illness were common symptoms, with 19/65 (29.2% patients diagnosed with pneumonia by chest radiography. All four adult patients had systemic influenza-like symptoms. Phylogenetic analysis of the complete genome revealed a close relationship with other HBoVs, and a more distant relationship with HBoV2 and HBoV3. Conclusions HBoV was detected from children and adults with ARTI from Guangzhou, southern China. Elderly people were also susceptive to HBoV. A single lineage of HBoV was detected among a wide age distribution of patients with ARTI.

[Parasitologic significance of the alteration of the causative Anisakidae worm and of the Pseudoterranova decipiens female immature adult worm, casting off the cuticles, and excreted from human in Kanazawa City].

Science.gov (United States)

Ishikura, H; Kikuchi, K; Akao, N; Doutei, M; Yagi, K; Takahashi, S; Sato, N

1995-09-01

We have been studying Anisakidae larvae, their intermediate hosts and their final hosts in the northern Japan Sea area. These larvae cause anisakidosis. According to the investigation, the recent burst of pseudoterranovosis in this area can be attributed to the increased presence of sea lions, which proliferate in the Arctic region, then migrate to the northern Japan Sea and eat the intermediate host fish. In a stomach of a male sea lion that was captured in February 1995, we found more than 4,500 Pseudoterranova decipiens. Although there is no known circumstance in which a human would consume an adult worm of Anisakis nematode, an astonishing case of this was found in Kanazawa; a female young adult Pseudoterranova decipiens undergoing the final metamorphosis was emitted from a patient. This indicates that the Anisakis larva can mature into the adult worm in humans. It is postulated that the Pseudoterranova decipiens larva is in the process of adapting to use humans as the final host.

The behavioural response of adult Petromyzon marinus to damage-released alarm and predator cues

Science.gov (United States)

Imre, István; Di Rocco, Richard; Belanger, Cowan; Brown, Grant; Johnson, Nicholas S.

2014-01-01

Using semi-natural enclosures, this study investigated (1) whether adult sea lamprey Petromyzon marinus show avoidance of damage-released conspecific cues, damage-released heterospecific cues and predator cues and (2) whether this is a general response to injured heterospecific fishes or a specific response to injured P. marinus. Ten replicate groups of 10 adult P. marinus, separated by sex, were exposed to one of the following nine stimuli: deionized water (control), extracts prepared from adult P. marinus, decayed adult P. marinus (conspecific stimuli), sympatric white sucker Catostomus commersonii, Amazon sailfin catfish Pterygoplichthys pardalis (heterospecific stimuli), 2-phenylethylamine (PEA HCl) solution, northern water snake Nerodia sipedon washing, human saliva (predator cues) and an adult P. marinus extract and human saliva combination (a damage-released conspecific cue and a predator cue). Adult P. marinus showed a significant avoidance response to the adult P. marinus extract as well as to C. commersonii, human saliva, PEA and the adult P. marinus extract and human saliva combination. For mobile P. marinus, the N. sipedon washing induced behaviour consistent with predator inspection. Exposure to the P. pardalis extract did not induce a significant avoidance response during the stimulus release period. Mobile adult female P. marinus showed a stronger avoidance behaviour than mobile adult male P. marinus in response to the adult P. marinus extract and the adult P. marinus extract and human saliva combination. The findings support the continued investigation of natural damage-released alarm cue and predator-based repellents for the behavioural manipulation of P. marinus populations in the Laurentian Great Lakes.

Adult Personality Development: Dynamics and Processes

OpenAIRE

Diehl, Manfred; Hooker, Karen

2013-01-01

The focus of this special issue of Research in Human Development is on adult personality and how personality may contribute to and be involved in adult development. Specifically, the contributions in this issue focus on the links between personality structures (e.g., traits) and personality processes (e.g., goal pursuit, self--regulation) and emphasize the contributions that intensive repeated measurement approaches can make to the understanding of personality and development across the adult...

Adult Learning, Economy and Society

DEFF Research Database (Denmark)

Olesen, Henning Salling

2010-01-01

The article relates the different types of adult education, continuing education and training to an overall societal context of socio-economic modernization by focussing on the multiple functions of adult learning. Each of well known empirical categories is seen in its historical relation to mode...... embracing form which set a new framework for human participation in the new global society....

Comparison of the Immunogenicity and Reactogenicity of Cervarix and Gardasil Human Papillomavirus Vaccines in HIV-Infected Adults

DEFF Research Database (Denmark)

Nielsen, Lars Toft; Storgaard, Merete; Müller, Martin

2013-01-01

Objectives. To compare the immunogenicity and reactogenicity of Cervarix(®) or Gardasil(®) Human Papillomavirus (HPV) vaccines in HIV-infected adults.Methods. A double-blind, controlled trial randomizing HIV-positive adults to receive three doses of Cervarix(®) or Gardasil(®) at 0, 1.5 and 6 months.......Results. Ninety-two participants were included in the study. Anti-HPV-18 antibody titers were higher in the Cervarix(®) group compared with the Gardasil(®) group at 7 and 12 months. No significant differences in anti-HPV-16 antibody titers were found among vaccine groups. Among Cervarix(®) vaccinees, women had...... higher anti-HPV-16/-18 antibody titers compared to men. No gender-specific differences in antibody titers were found in the Gardasil(®) group. Mild injection site reactions were more common in the Cervarix(®) group than in the Gardasil(®) group (91.1% vs. 69.6%; P=.02). No serious adverse events occurred...

Cortical cell and neuron density estimates in one chimpanzee hemisphere.

Science.gov (United States)

Collins, Christine E; Turner, Emily C; Sawyer, Eva Kille; Reed, Jamie L; Young, Nicole A; Flaherty, David K; Kaas, Jon H

2016-01-19

The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm(2) of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates.

Neocortical development as an evolutionary platform for intragenomic conflict

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Eric eLewitus

2013-04-01

Full Text Available Embryonic development in mammals has evolved a platform for genomic conflict between mothers and embryos and, by extension, between maternal and paternal genomes. The evolutionary interests of the mother and embryo may be maximized through the promotion of sex-chromosome genes and imprinted alleles, resulting in the rapid evolution of postzygotic phenotypes preferential to either the maternal or paternal genome. In eutherian mammals, extraordinary in utero maternal investment in the brain, and neocortex especially, suggests that convergent evolution of an expanded mammalian neocortex along divergent lineages may be explained, in part, by parent-of-origin-linked gene expression arising from parent-offspring conflict. The influence of this conflict on neocortical development and evolution, however, has not been investigated at the genomic level. In this hypothesis and theory article, we provide preliminary evidence for positive selection in humans in the regions of two platforms of intragenomic conflict – chromosomes 15q11-q13 and X – and explore the potential relevance of cis-regulated imprinted domains to neocortical expansion in mammalian evolution. We present the hypothesis that maternal- and paternal-specific pressures on the developing neocortex compete intragenomically to influence neocortical expansion in mammalian evolution.

Motivation and Adult Education.

Science.gov (United States)

Taylor, J. Rodney

1982-01-01

The author reviews theories of human motivation: Lewin's force field analysis, Skinner's operant reinforcement theory, and Maslow's hierarchy of needs. He then extracts the implications of these theories for adult learning. SK)

Prevalence and correlates of beta human papillomavirus detection in fingernail samples from mid-adult women

Directory of Open Access Journals (Sweden)

Rachel L. Winer

2018-06-01

Full Text Available Cutaneous human papillomaviruses (HPVs have not been evaluated in fingernails from healthy individuals. To determine prevalence and correlates of β-HPVs in fingernails from healthy mid-adult women, we tested archived samples collected from 2011 to 2012 using a multiplex PCR combined with Luminex technology for 46 β-HPV genotypes. One hundred thirteen (61.1% of 185 fingernail samples were positive for β-HPV, and the median number of types detected in positive samples was 2 (interquartile range: 1–4. The most common genotypes detected were HPV-23 (β−2 (13.5%, HPV-38 (β−2 (13.0%, HPV-5 (β−1 (9.2%, HPV-107 (β−2 (8.7%, and HPV-120 (β−2 (8.7%. In multivariate analysis, β-HPV detection was associated with age (prevalence ratio [PR] for women 40–51 years versus 30–39 years = 1.30, 95% CI: 1.05–1.62 and race (PR for non-white versus white race = 0.65, 95% CI: 0.45–0.94. The prevalence of β-HPV in fingernail samples from healthy mid-adult women was similar to the prevalence of β-HPV reported at other cutaneous sites in prior studies. We did not identify any significant health or sexual behavior predictors of β-HPV detection in fingernails. Our results support the hypothesis that fingers may serve as a source of transmission or autoinoculation of cutaneous HPVs to other anatomic sites. Keywords: Fingernails, Women, Beta-HPV, Prevalence, Mid-adult, Risk factor

Empowering Adult Learners. NIF Literacy Program Helps ABE Accomplish Human Development Mission.

Science.gov (United States)

Hurley, Mary E.

1991-01-01

The National Issues Forum's Literacy Program uses study circles and group discussion to promote empowerment and enhance adult literacy through civic education. The program has helped the Westonka (Minnesota) Adult Basic Education project accomplish its mission and has expanded the staff's view of adult learning. (SK)

Three-dimensional stereotactic atlas of the adult human skull correlated with the brain, cranial nerves, and intracranial vasculature.

Science.gov (United States)

Nowinski, Wieslaw L; Thaung, Thant Shoon Let; Chua, Beng Choon; Yi, Su Hnin Wut; Ngai, Vincent; Yang, Yili; Chrzan, Robert; Urbanik, Andrzej

2015-05-15

Although the adult human skull is a complex and multifunctional structure, its 3D, complete, realistic, and stereotactic atlas has not yet been created. This work addresses the construction of a 3D interactive atlas of the adult human skull spatially correlated with the brain, cranial nerves, and intracranial vasculature. The process of atlas construction included computed tomography (CT) high-resolution scan acquisition, skull extraction, skull parcellation, 3D disarticulated bone surface modeling, 3D model simplification, brain-skull registration, 3D surface editing, 3D surface naming and color-coding, integration of the CT-derived 3D bony models with the existing brain atlas, and validation. The virtual skull model created is complete with all 29 bones, including the auditory ossicles (being among the smallest bones). It contains all typical bony features and landmarks. The created skull model is superior to the existing skull models in terms of completeness, realism, and integration with the brain along with blood vessels and cranial nerves. This skull atlas is valuable for medical students and residents to easily get familiarized with the skull and surrounding anatomy with a few clicks. The atlas is also useful for educators to prepare teaching materials. It may potentially serve as a reference aid in the reading and operating rooms. Copyright © 2015 Elsevier B.V. All rights reserved.

Defining the role of common variation in the genomic and biological architecture of adult human height

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Chu, Audrey Y; Estrada, Karol; Luan, Jian’an; Kutalik, Zoltán; Amin, Najaf; Buchkovich, Martin L; Croteau-Chonka, Damien C; Day, Felix R; Duan, Yanan; Fall, Tove; Fehrmann, Rudolf; Ferreira, Teresa; Jackson, Anne U; Karjalainen, Juha; Lo, Ken Sin; Locke, Adam E; Mägi, Reedik; Mihailov, Evelin; Porcu, Eleonora; Randall, Joshua C; Scherag, André; Vinkhuyzen, Anna AE; Westra, Harm-Jan; Winkler, Thomas W; Workalemahu, Tsegaselassie; Zhao, Jing Hua; Absher, Devin; Albrecht, Eva; Anderson, Denise; Baron, Jeffrey; Beekman, Marian; Demirkan, Ayse; Ehret, Georg B; Feenstra, Bjarke; Feitosa, Mary F; Fischer, Krista; Fraser, Ross M; Goel, Anuj; Gong, Jian; Justice, Anne E; Kanoni, Stavroula; Kleber, Marcus E; Kristiansson, Kati; Lim, Unhee; Lotay, Vaneet; Lui, Julian C; Mangino, Massimo; Leach, Irene Mateo; Medina-Gomez, Carolina; Nalls, Michael A; Nyholt, Dale R; Palmer, Cameron D; Pasko, Dorota; Pechlivanis, Sonali; Prokopenko, Inga; Ried, Janina S; Ripke, Stephan; Shungin, Dmitry; Stancáková, Alena; Strawbridge, Rona J; Sung, Yun Ju; Tanaka, Toshiko; Teumer, Alexander; Trompet, Stella; van der Laan, Sander W; van Setten, Jessica; Van Vliet-Ostaptchouk, Jana V; Wang, Zhaoming; Yengo, Loïc; Zhang, Weihua; Afzal, Uzma; Ärnlöv, Johan; Arscott, Gillian M; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J; Berne, Christian; Blüher, Matthias; Bolton, Jennifer L; Böttcher, Yvonne; Boyd, Heather A; Bruinenberg, Marcel; Buckley, Brendan M; Buyske, Steven; Caspersen, Ida H; Chines, Peter S; Clarke, Robert; Claudi-Boehm, Simone; Cooper, Matthew; Daw, E Warwick; De Jong, Pim A; Deelen, Joris; Delgado, Graciela; Denny, Josh C; Dhonukshe-Rutten, Rosalie; Dimitriou, Maria; Doney, Alex SF; Dörr, Marcus; Eklund, Niina; Eury, Elodie; Folkersen, Lasse; Garcia, Melissa E; Geller, Frank; Giedraitis, Vilmantas; Go, Alan S; Grallert, Harald; Grammer, Tanja B; Gräßler, Jürgen; Grönberg, Henrik; de Groot, Lisette C.P.G.M.; Groves, Christopher J; Haessler, Jeffrey; Hall, Per; Haller, Toomas; Hallmans, Goran; Hannemann, Anke; Hartman, Catharina A; Hassinen, Maija; Hayward, Caroline; Heard-Costa, Nancy L; Helmer, Quinta; Hemani, Gibran; Henders, Anjali K; Hillege, Hans L; Hlatky, Mark A; Hoffmann, Wolfgang; Hoffmann, Per; Holmen, Oddgeir; Houwing-Duistermaat, Jeanine J; Illig, Thomas; Isaacs, Aaron; James, Alan L; Jeff, Janina; Johansen, Berit; Johansson, Åsa; Jolley, Jennifer; Juliusdottir, Thorhildur; Junttila, Juhani; Kho, Abel N; Kinnunen, Leena; Klopp, Norman; Kocher, Thomas; Kratzer, Wolfgang; Lichtner, Peter; Lind, Lars; Lindström, Jaana; Lobbens, Stéphane; Lorentzon, Mattias; Lu, Yingchang; Lyssenko, Valeriya; Magnusson, Patrik KE; Mahajan, Anubha; Maillard, Marc; McArdle, Wendy L; McKenzie, Colin A; McLachlan, Stela; McLaren, Paul J; Menni, Cristina; Merger, Sigrun; Milani, Lili; Moayyeri, Alireza; Monda, Keri L; Morken, Mario A; Müller, Gabriele; Müller-Nurasyid, Martina; Musk, Arthur W; Narisu, Narisu; Nauck, Matthias; Nolte, Ilja M; Nöthen, Markus M; Oozageer, Laticia; Pilz, Stefan; Rayner, Nigel W; Renstrom, Frida; Robertson, Neil R; Rose, Lynda M; Roussel, Ronan; Sanna, Serena; Scharnagl, Hubert; Scholtens, Salome; Schumacher, Fredrick R; Schunkert, Heribert; Scott, Robert A; Sehmi, Joban; Seufferlein, Thomas; Shi, Jianxin; Silventoinen, Karri; Smit, Johannes H; Smith, Albert Vernon; Smolonska, Joanna; Stanton, Alice V; Stirrups, Kathleen; Stott, David J; Stringham, Heather M; Sundström, Johan; Swertz, Morris A; Syvänen, Ann-Christine; Tayo, Bamidele O; Thorleifsson, Gudmar; Tyrer, Jonathan P; van Dijk, Suzanne; van Schoor, Natasja M; van der Velde, Nathalie; van Heemst, Diana; van Oort, Floor VA; Vermeulen, Sita H; Verweij, Niek; Vonk, Judith M; Waite, Lindsay L; Waldenberger, Melanie; Wennauer, Roman; Wilkens, Lynne R; Willenborg, Christina; Wilsgaard, Tom; Wojczynski, Mary K; Wong, Andrew; Wright, Alan F; Zhang, Qunyuan; Arveiler, Dominique; Bakker, Stephan JL; Beilby, John; Bergman, Richard N; Bergmann, Sven; Biffar, Reiner; Blangero, John; Boomsma, Dorret I; Bornstein, Stefan R; Bovet, Pascal; Brambilla, Paolo; Brown, Morris J; Campbell, Harry; Caulfield, Mark J; Chakravarti, Aravinda; Collins, Rory; Collins, Francis S; Crawford, Dana C; Cupples, L Adrienne; Danesh, John; de Faire, Ulf; den Ruijter, Hester M; Erbel, Raimund; Erdmann, Jeanette; Eriksson, Johan G; Farrall, Martin; Ferrannini, Ele; Ferrières, Jean; Ford, Ian; Forouhi, Nita G; Forrester, Terrence; Gansevoort, Ron T; Gejman, Pablo V; Gieger, Christian; Golay, Alain; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Haas, David W; Hall, Alistair S; Harris, Tamara B; Hattersley, Andrew T; Heath, Andrew C; Hengstenberg, Christian; Hicks, Andrew A; Hindorff, Lucia A; Hingorani, Aroon D; Hofman, Albert; Hovingh, G Kees; Humphries, Steve E; Hunt, Steven C; Hypponen, Elina; Jacobs, Kevin B; Jarvelin, Marjo-Riitta; Jousilahti, Pekka; Jula, Antti M; Kaprio, Jaakko; Kastelein, John JP; Kayser, Manfred; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M; Kiemeney, Lambertus A; Kooner, Jaspal S; Kooperberg, Charles; Koskinen, Seppo; Kovacs, Peter; Kraja, Aldi T; Kumari, Meena; Kuusisto, Johanna; Lakka, Timo A; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lupoli, Sara; Madden, Pamela AF; Männistö, Satu; Manunta, Paolo; Marette, André; Matise, Tara C; McKnight, Barbara; Meitinger, Thomas; Moll, Frans L; Montgomery, Grant W; Morris, Andrew D; Morris, Andrew P; Murray, Jeffrey C; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J; Ong, Ken K; Ouwehand, Willem H; Pasterkamp, Gerard; Peters, Annette; Pramstaller, Peter P; Price, Jackie F; Qi, Lu; Raitakari, Olli T; Rankinen, Tuomo; Rao, DC; Rice, Treva K; Ritchie, Marylyn; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J; Saramies, Jouko; Sarzynski, Mark A; Schwarz, Peter EH; Sebert, Sylvain; Sever, Peter; Shuldiner, Alan R; Sinisalo, Juha; Steinthorsdottir, Valgerdur; Stolk, Ronald P; Tardif, Jean-Claude; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Virtamo, Jarmo; Vohl, Marie-Claude; Amouyel, Philippe; Asselbergs, Folkert W; Assimes, Themistocles L; Bochud, Murielle; Boehm, Bernhard O; Boerwinkle, Eric; Bottinger, Erwin P; Bouchard, Claude; Cauchi, Stéphane; Chambers, John C; Chanock, Stephen J; Cooper, Richard S; de Bakker, Paul IW; Dedoussis, George; Ferrucci, Luigi; Franks, Paul W; Froguel, Philippe; Groop, Leif C; Haiman, Christopher A; Hamsten, Anders; Hayes, M Geoffrey; Hui, Jennie; Hunter, David J.; Hveem, Kristian; Jukema, J Wouter; Kaplan, Robert C; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; Martin, Nicholas G; März, Winfried; Melbye, Mads; Moebus, Susanne; Munroe, Patricia B; Njølstad, Inger; Oostra, Ben A; Palmer, Colin NA; Pedersen, Nancy L; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Powell, Joseph E; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Reinmaa, Eva; Ridker, Paul M; Rivadeneira, Fernando; Rotter, Jerome I; Saaristo, Timo E; Saleheen, Danish; Schlessinger, David; Slagboom, P Eline; Snieder, Harold; Spector, Tim D; Strauch, Konstantin; Stumvoll, Michael; Tuomilehto, Jaakko; Uusitupa, Matti; van der Harst, Pim; Völzke, Henry; Walker, Mark; Wareham, Nicholas J; Watkins, Hugh; Wichmann, H-Erich; Wilson, James F; Zanen, Pieter; Deloukas, Panos; Heid, Iris M; Lindgren, Cecilia M; Mohlke, Karen L; Speliotes, Elizabeth K; Thorsteinsdottir, Unnur; Barroso, Inês; Fox, Caroline S; North, Kari E; Strachan, David P; Beckmann, Jacques S.; Berndt, Sonja I; Boehnke, Michael; Borecki, Ingrid B; McCarthy, Mark I; Metspalu, Andres; Stefansson, Kari; Uitterlinden, André G; van Duijn, Cornelia M; Franke, Lude; Willer, Cristen J; Price, Alkes L.; Lettre, Guillaume; Loos, Ruth JF; Weedon, Michael N; Ingelsson, Erik; O’Connell, Jeffrey R; Abecasis, Goncalo R; Chasman, Daniel I; Goddard, Michael E

2014-01-01

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explain one-fifth of heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ~2,000, ~3,700 and ~9,500 SNPs explained ~21%, ~24% and ~29% of phenotypic variance. Furthermore, all common variants together captured the majority (60%) of heritability. The 697 variants clustered in 423 loci enriched for genes, pathways, and tissue-types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin, and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants. PMID:25282103

Defining the role of common variation in the genomic and biological architecture of adult human height.

Science.gov (United States)

Wood, Andrew R; Esko, Tonu; Yang, Jian; Vedantam, Sailaja; Pers, Tune H; Gustafsson, Stefan; Chu, Audrey Y; Estrada, Karol; Luan, Jian'an; Kutalik, Zoltán; Amin, Najaf; Buchkovich, Martin L; Croteau-Chonka, Damien C; Day, Felix R; Duan, Yanan; Fall, Tove; Fehrmann, Rudolf; Ferreira, Teresa; Jackson, Anne U; Karjalainen, Juha; Lo, Ken Sin; Locke, Adam E; Mägi, Reedik; Mihailov, Evelin; Porcu, Eleonora; Randall, Joshua C; Scherag, André; Vinkhuyzen, Anna A E; Westra, Harm-Jan; Winkler, Thomas W; Workalemahu, Tsegaselassie; Zhao, Jing Hua; Absher, Devin; Albrecht, Eva; Anderson, Denise; Baron, Jeffrey; Beekman, Marian; Demirkan, Ayse; Ehret, Georg B; Feenstra, Bjarke; Feitosa, Mary F; Fischer, Krista; Fraser, Ross M; Goel, Anuj; Gong, Jian; Justice, Anne E; Kanoni, Stavroula; Kleber, Marcus E; Kristiansson, Kati; Lim, Unhee; Lotay, Vaneet; Lui, Julian C; Mangino, Massimo; Mateo Leach, Irene; Medina-Gomez, Carolina; Nalls, Michael A; Nyholt, Dale R; Palmer, Cameron D; Pasko, Dorota; Pechlivanis, Sonali; Prokopenko, Inga; Ried, Janina S; Ripke, Stephan; Shungin, Dmitry; Stancáková, Alena; Strawbridge, Rona J; Sung, Yun Ju; Tanaka, Toshiko; Teumer, Alexander; Trompet, Stella; van der Laan, Sander W; van Setten, Jessica; Van Vliet-Ostaptchouk, Jana V; Wang, Zhaoming; Yengo, Loïc; Zhang, Weihua; Afzal, Uzma; Arnlöv, Johan; Arscott, Gillian M; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J; Berne, Christian; Blüher, Matthias; Bolton, Jennifer L; Böttcher, Yvonne; Boyd, Heather A; Bruinenberg, Marcel; Buckley, Brendan M; Buyske, Steven; Caspersen, Ida H; Chines, Peter S; Clarke, Robert; Claudi-Boehm, Simone; Cooper, Matthew; Daw, E Warwick; De Jong, Pim A; Deelen, Joris; Delgado, Graciela; Denny, Josh C; Dhonukshe-Rutten, Rosalie; Dimitriou, Maria; Doney, Alex S F; Dörr, Marcus; Eklund, Niina; Eury, Elodie; Folkersen, Lasse; Garcia, Melissa E; Geller, Frank; Giedraitis, Vilmantas; Go, Alan S; Grallert, Harald; Grammer, Tanja B; Gräßler, Jürgen; Grönberg, Henrik; de Groot, Lisette C P G M; Groves, Christopher J; Haessler, Jeffrey; Hall, Per; Haller, Toomas; Hallmans, Goran; Hannemann, Anke; Hartman, Catharina A; Hassinen, Maija; Hayward, Caroline; Heard-Costa, Nancy L; Helmer, Quinta; Hemani, Gibran; Henders, Anjali K; Hillege, Hans L; Hlatky, Mark A; Hoffmann, Wolfgang; Hoffmann, Per; Holmen, Oddgeir; Houwing-Duistermaat, Jeanine J; Illig, Thomas; Isaacs, Aaron; James, Alan L; Jeff, Janina; Johansen, Berit; Johansson, Åsa; Jolley, Jennifer; Juliusdottir, Thorhildur; Junttila, Juhani; Kho, Abel N; Kinnunen, Leena; Klopp, Norman; Kocher, Thomas; Kratzer, Wolfgang; Lichtner, Peter; Lind, Lars; Lindström, Jaana; Lobbens, Stéphane; Lorentzon, Mattias; Lu, Yingchang; Lyssenko, Valeriya; Magnusson, Patrik K E; Mahajan, Anubha; Maillard, Marc; McArdle, Wendy L; McKenzie, Colin A; McLachlan, Stela; McLaren, Paul J; Menni, Cristina; Merger, Sigrun; Milani, Lili; Moayyeri, Alireza; Monda, Keri L; Morken, Mario A; Müller, Gabriele; Müller-Nurasyid, Martina; Musk, Arthur W; Narisu, Narisu; Nauck, Matthias; Nolte, Ilja M; Nöthen, Markus M; Oozageer, Laticia; Pilz, Stefan; Rayner, Nigel W; Renstrom, Frida; Robertson, Neil R; Rose, Lynda M; Roussel, Ronan; Sanna, Serena; Scharnagl, Hubert; Scholtens, Salome; Schumacher, Fredrick R; Schunkert, Heribert; Scott, Robert A; Sehmi, Joban; Seufferlein, Thomas; Shi, Jianxin; Silventoinen, Karri; Smit, Johannes H; Smith, Albert Vernon; Smolonska, Joanna; Stanton, Alice V; Stirrups, Kathleen; Stott, David J; Stringham, Heather M; Sundström, Johan; Swertz, Morris A; Syvänen, Ann-Christine; Tayo, Bamidele O; Thorleifsson, Gudmar; Tyrer, Jonathan P; van Dijk, Suzanne; van Schoor, Natasja M; van der Velde, Nathalie; van Heemst, Diana; van Oort, Floor V A; Vermeulen, Sita H; Verweij, Niek; Vonk, Judith M; Waite, Lindsay L; Waldenberger, Melanie; Wennauer, Roman; Wilkens, Lynne R; Willenborg, Christina; Wilsgaard, Tom; Wojczynski, Mary K; Wong, Andrew; Wright, Alan F; Zhang, Qunyuan; Arveiler, Dominique; Bakker, Stephan J L; Beilby, John; Bergman, Richard N; Bergmann, Sven; Biffar, Reiner; Blangero, John; Boomsma, Dorret I; Bornstein, Stefan R; Bovet, Pascal; Brambilla, Paolo; Brown, Morris J; Campbell, Harry; Caulfield, Mark J; Chakravarti, Aravinda; Collins, Rory; Collins, Francis S; Crawford, Dana C; Cupples, L Adrienne; Danesh, John; de Faire, Ulf; den Ruijter, Hester M; Erbel, Raimund; Erdmann, Jeanette; Eriksson, Johan G; Farrall, Martin; Ferrannini, Ele; Ferrières, Jean; Ford, Ian; Forouhi, Nita G; Forrester, Terrence; Gansevoort, Ron T; Gejman, Pablo V; Gieger, Christian; Golay, Alain; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Haas, David W; Hall, Alistair S; Harris, Tamara B; Hattersley, Andrew T; Heath, Andrew C; Hengstenberg, Christian; Hicks, Andrew A; Hindorff, Lucia A; Hingorani, Aroon D; Hofman, Albert; Hovingh, G Kees; Humphries, Steve E; Hunt, Steven C; Hypponen, Elina; Jacobs, Kevin B; Jarvelin, Marjo-Riitta; Jousilahti, Pekka; Jula, Antti M; Kaprio, Jaakko; Kastelein, John J P; Kayser, Manfred; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M; Kiemeney, Lambertus A; Kooner, Jaspal S; Kooperberg, Charles; Koskinen, Seppo; Kovacs, Peter; Kraja, Aldi T; Kumari, Meena; Kuusisto, Johanna; Lakka, Timo A; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lupoli, Sara; Madden, Pamela A F; Männistö, Satu; Manunta, Paolo; Marette, André; Matise, Tara C; McKnight, Barbara; Meitinger, Thomas; Moll, Frans L; Montgomery, Grant W; Morris, Andrew D; Morris, Andrew P; Murray, Jeffrey C; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J; Ong, Ken K; Ouwehand, Willem H; Pasterkamp, Gerard; Peters, Annette; Pramstaller, Peter P; Price, Jackie F; Qi, Lu; Raitakari, Olli T; Rankinen, Tuomo; Rao, D C; Rice, Treva K; Ritchie, Marylyn; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J; Saramies, Jouko; Sarzynski, Mark A; Schwarz, Peter E H; Sebert, Sylvain; Sever, Peter; Shuldiner, Alan R; Sinisalo, Juha; Steinthorsdottir, Valgerdur; Stolk, Ronald P; Tardif, Jean-Claude; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Virtamo, Jarmo; Vohl, Marie-Claude; Amouyel, Philippe; Asselbergs, Folkert W; Assimes, Themistocles L; Bochud, Murielle; Boehm, Bernhard O; Boerwinkle, Eric; Bottinger, Erwin P; Bouchard, Claude; Cauchi, Stéphane; Chambers, John C; Chanock, Stephen J; Cooper, Richard S; de Bakker, Paul I W; Dedoussis, George; Ferrucci, Luigi; Franks, Paul W; Froguel, Philippe; Groop, Leif C; Haiman, Christopher A; Hamsten, Anders; Hayes, M Geoffrey; Hui, Jennie; Hunter, David J; Hveem, Kristian; Jukema, J Wouter; Kaplan, Robert C; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; Martin, Nicholas G; März, Winfried; Melbye, Mads; Moebus, Susanne; Munroe, Patricia B; Njølstad, Inger; Oostra, Ben A; Palmer, Colin N A; Pedersen, Nancy L; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Powell, Joseph E; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Reinmaa, Eva; Ridker, Paul M; Rivadeneira, Fernando; Rotter, Jerome I; Saaristo, Timo E; Saleheen, Danish; Schlessinger, David; Slagboom, P Eline; Snieder, Harold; Spector, Tim D; Strauch, Konstantin; Stumvoll, Michael; Tuomilehto, Jaakko; Uusitupa, Matti; van der Harst, Pim; Völzke, Henry; Walker, Mark; Wareham, Nicholas J; Watkins, Hugh; Wichmann, H-Erich; Wilson, James F; Zanen, Pieter; Deloukas, Panos; Heid, Iris M; Lindgren, Cecilia M; Mohlke, Karen L; Speliotes, Elizabeth K; Thorsteinsdottir, Unnur; Barroso, Inês; Fox, Caroline S; North, Kari E; Strachan, David P; Beckmann, Jacques S; Berndt, Sonja I; Boehnke, Michael; Borecki, Ingrid B; McCarthy, Mark I; Metspalu, Andres; Stefansson, Kari; Uitterlinden, André G; van Duijn, Cornelia M; Franke, Lude; Willer, Cristen J; Price, Alkes L; Lettre, Guillaume; Loos, Ruth J F; Weedon, Michael N; Ingelsson, Erik; O'Connell, Jeffrey R; Abecasis, Goncalo R; Chasman, Daniel I; Goddard, Michael E; Visscher, Peter M; Hirschhorn, Joel N; Frayling, Timothy M

2014-11-01

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Human Recombinant Peptide Sponge Enables Novel, Less Invasive Cell Therapy for Ischemic Stroke

Directory of Open Access Journals (Sweden)

Michiyuki Miyamoto

2018-01-01

Full Text Available Bone marrow stromal cell (BMSC transplantation has the therapeutic potential for ischemic stroke. However, it is unclear which delivery routes would yield both safety and maximal therapeutic benefits. We assessed whether a novel recombinant peptide (RCP sponge, that resembles human collagen, could act as a less invasive and beneficial scaffold in cell therapy for ischemic stroke. BMSCs from green fluorescent protein-transgenic rats were cultured and Sprague–Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAo. A BMSC-RCP sponge construct was transplanted onto the ipsilateral intact neocortex 7 days after MCAo. A BMSC suspension or vehicle was transplanted into the ipsilateral striatum. Rat motor function was serially evaluated and histological analysis was performed 5 weeks after transplantation. The results showed that BMSCs could proliferate well in the RCP sponge and the BMSC-RCP sponge significantly promoted functional recovery, compared with the vehicle group. Histological analysis revealed that the RCP sponge provoked few inflammatory reactions in the host brain. Moreover, some BMSCs migrated to the peri-infarct area and differentiated into neurons in the BMSC-RCP sponge group. These findings suggest that the RCP sponge may be a promising candidate for animal protein-free scaffolds in cell therapy for ischemic stroke in humans.

Effect of exercise on fluoride metabolism in adult humans: a pilot study.

Science.gov (United States)

V Zohoori, Fatemeh; Innerd, Alison; Azevedo, Liane B; Whitford, Gary M; Maguire, Anne

2015-11-19

An understanding of all aspects of fluoride metabolism is critical to identify its biological effects and avoid fluoride toxicity in humans. Fluoride metabolism and subsequently its body retention may be affected by physiological responses to acute exercise. This pilot study investigated the effect of exercise on plasma fluoride concentration, urinary fluoride excretion and fluoride renal clearance following no exercise and three exercise intensity conditions in nine healthy adults after taking a 1-mg Fluoride tablet. After no, light, moderate and vigorous exercise, respectively, the mean (SD) baseline-adjusted i) plasma fluoride concentration was 9.6(6.3), 11.4(6.3), 15.6(7.7) and 14.9(10.0) ng/ml; ii) rate of urinary fluoride excretion over 0-8 h was 46(15), 44(22), 34(17) and 36(17) μg/h; and iii) rate of fluoride renal clearance was 26.5(9.0), 27.2(30.4), 13.1(20.4) and 18.3(34.9) ml/min. The observed trend of a rise in plasma fluoride concentration and decline in rate of fluoride renal clearance with increasing exercise intensity needs to be investigated in a larger trial. This study, which provides the first data on the effect of exercise with different intensities on fluoride metabolism in humans, informs sample size planning for any subsequent definitive trial, by providing a robust estimate of the variability of the effect.

A Window Toward the World: Older Adults' Experiences of Becoming in Health and Developing as Human Beings Through Interacting With Others Using Real Video Communication.

Science.gov (United States)

Hemberg, Jessica; Santamäki Fischer, Regina

The population in the Nordic countries, as well as globally, is increasingly becoming older. Concurrently, with an increased aging population, there is an increase in poor health and loneliness among older adults. The aim of this study was to uncover, from a caring science perspective, community-living older adults' experiences of interacting with others via real video communication. The study uses a hermeneutical approach. The material consists of interviews with older adults regarding their experiences of using real video communication. The texts were interpreted through hermeneutical reading. Study participation and data storage and handling for research purposes were approved by the participants when they provided their informed consent. Ethical permission to conduct this study was granted by a research board. The findings uncovered that welfare technology offers a metaphor-a window toward the world-that comprises the overarching core theme "Being in a movement toward becoming a unity as a human being," and 3 main themes: "Alleviating suffering through beating involuntary solitude," "Being in the world as an equal and dignified human being," and "Dedicating new perspectives and meaning in life." Welfare technology seems to be an important means to improve the quality of life for older adults living at home. Welfare technology enables older people to be in contact with other people in an easy way. Further research is needed to uncover issues of welfare technology from different perspectives.

Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior

Science.gov (United States)

Vetreno, Ryan P.; Broadwater, Margaret A.; Robinson, Donita L.

2016-01-01

Adolescence is a developmental period when physical and cognitive abilities are optimized, when social skills are consolidated, and when sexuality, adolescent behaviors, and frontal cortical functions mature to adult levels. Adolescents also have unique responses to alcohol compared with adults, being less sensitive to ethanol sedative–motor responses that most likely contribute to binge drinking and blackouts. Population studies find that an early age of drinking onset correlates with increased lifetime risks for the development of alcohol dependence, violence, and injuries. Brain synapses, myelination, and neural circuits mature in adolescence to adult levels in parallel with increased reflection on the consequence of actions and reduced impulsivity and thrill seeking. Alcohol binge drinking could alter human development, but variations in genetics, peer groups, family structure, early life experiences, and the emergence of psychopathology in humans confound studies. As adolescence is common to mammalian species, preclinical models of binge drinking provide insight into the direct impact of alcohol on adolescent development. This review relates human findings to basic science studies, particularly the preclinical studies of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium. These studies focus on persistent adult changes in neurobiology and behavior following adolescent intermittent ethanol (AIE), a model of underage drinking. NADIA studies and others find that AIE results in the following: increases in adult alcohol drinking, disinhibition, and social anxiety; altered adult synapses, cognition, and sleep; reduced adult neurogenesis, cholinergic, and serotonergic neurons; and increased neuroimmune gene expression and epigenetic modifiers of gene expression. Many of these effects are specific to adolescents and not found in parallel adult studies. AIE can cause a persistence of adolescent-like synaptic physiology, behavior, and sensitivity

Nanosized fibers' effect on adult human articular chondrocytes behavior

International Nuclear Information System (INIS)

Stenhamre, Hanna; Thorvaldsson, Anna; Enochson, Lars; Walkenström, Pernilla; Lindahl, Anders; Brittberg, Mats; Gatenholm, Paul

2013-01-01

Tissue engineering with chondrogenic cell based therapies is an expanding field with the intention of treating cartilage defects. It has been suggested that scaffolds used in cartilage tissue engineering influence cellular behavior and thus the long-term clinical outcome. The objective of this study was to assess whether chondrocyte attachment, proliferation and post-expansion re-differentiation could be influenced by the size of the fibers presented to the cells in a scaffold. Polylactic acid (PLA) scaffolds with different fiber morphologies were produced, i.e. microfiber (MS) scaffolds as well as nanofiber-coated microfiber scaffold (NMS). Adult human articular chondrocytes were cultured in the scaffolds in vitro up to 28 days, and the resulting constructs were assessed histologically, immunohistochemically, and biochemically. Attachment of cells and serum proteins to the scaffolds was affected by the architecture. The results point toward nano-patterning onto the microfibers influencing proliferation of the chondrocytes, and the overall 3D environment having a greater influence on the re-differentiation. In the efforts of finding the optimal scaffold for cartilage tissue engineering, studies as the current contribute to the knowledge of how to affect and control chondrocytes behavior. - Highlights: ► Chondrocyte behavior in nanofiber-coated microfiber versus microfiber scaffolds ► High porosity (> 90%) and large pore sizes (a few hundred μm) of nanofibrous scaffolds ► Proliferation enhanced by presence of nanofibers ► Differentiation not significantly affected ► Cell attachment improved in presence of both nanofibers and serum

A century of trends in adult human height

DEFF Research Database (Denmark)

Damsgaard, Camilla Trab; Michaelsen, Kim F.; Molbo, Drude

2016-01-01

in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5-22.7) and 16.5 cm (13.3-19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over...... the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8-144.8). The height differential between the tallest...... and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries....

Procedures for ambient-pressure and tympanometric tests of aural acoustic reflectance and admittance in human infants and adults

Science.gov (United States)

Keefe, Douglas H.; Hunter, Lisa L.; Feeney, M. Patrick; Fitzpatrick, Denis F.

2015-01-01

Procedures are described to measure acoustic reflectance and admittance in human adult and infant ears at frequencies from 0.2 to 8 kHz. Transfer functions were measured at ambient pressure in the ear canal, and as down- or up-swept tympanograms. Acoustically estimated ear-canal area was used to calculate ear reflectance, which was parameterized by absorbance and group delay over all frequencies (and pressures), with substantial data reduction for tympanograms. Admittance measured at the probe tip in adults was transformed into an equivalent admittance at the eardrum using a transmission-line model for an ear canal with specified area and ear-canal length. Ear-canal length was estimated from group delay around the frequency above 2 kHz of minimum absorbance. Illustrative measurements in ears with normal function are described for an adult, and two infants at 1 month of age with normal hearing and a conductive hearing loss. The sensitivity of this equivalent eardrum admittance was calculated for varying estimates of area and length. Infant-ear patterns of absorbance peaks aligned in frequency with dips in group delay were explained by a model of resonant canal-wall mobility. Procedures will be applied in a large study of wideband clinical diagnosis and monitoring of middle-ear and cochlear function. PMID:26723319

Novel use of levodopa in human immunodeficiency virus encephalopathy-mediated parkinsonism in an adult

Directory of Open Access Journals (Sweden)

M F Devine

2018-01-01

Full Text Available We report a case of a 36-year-old man with a medical history of human immunodeficiency virus (HIV infection who presented with hypomimia, hypophonia, bradykinesia, rigidity, and freezing of gait. His clinical presentation and magnetic resonance imaging were consistent with HIV encephalopathy with involvement of the bilateral basal ganglia and diffuse leukoencephalopathy. We initiated a trial of carbidopa-levodopa. The dose was escalated to 1050 mg levodopa daily. Amantadine was also started. The patient was closely monitored for behavioral, neurological, or systemic side effects. He tolerated therapy well without adverse effects. The patient's neurological status significantly improved with levodopa, including hypomimia, hypophonia, bradykinesia, and fluidity of gait. This case demonstrates that carbidopa-levodopa can be safely utilized to manage parkinsonism in an adult patient with HIV encephalopathy.

Diversity in human hair growth, diameter, colour and shape. An in vivo study on young adults from 24 different ethnic groups observed in the five continents.

Science.gov (United States)

Loussouarn, Geneviève; Lozano, Isabelle; Panhard, Ségolène; Collaudin, Catherine; El Rawadi, Charles; Genain, Gilles

2016-04-01

Based on previous findings, from a worldwide study, classified the shapes of human hair into 8 major types, from straight to highly curly. This clearly extended the usual classification of hair into African, Asian or Caucasian types. However, determinations of hair growth parameters and hair density were excluded from such studies. To measure and compare the hair growth profiles of young adults without alopecia living in the five continents. 2249 young adults (18-35 years, females and males) without alopecia, originating from 24 various human ethnic groups were included in the study. Total hair density, telogen percentage and growth rate on three different scalp areas were measured, using non-invasive validated techniques. Natural hair colour level, curliness and hair diameter were additionally recorded, when practically possible. Diversity in hair growth parameters among the entire cohort was a key finding, with differences linked to scalp area, gender and geographic origin. Statistical approaches depicted African hair as having lower density and a slower growth rate. Asian hair showed a thicker diameter, with faster growth. Caucasian hair showed a high total hair density. On the one hand, this inter-continental study of hair growth parameters provides initial valuable base-line data on hair in young adults without alopecia, and on the other hand, further extends our knowledge of this unique human appendage, with some mosaic features, observed worldwide.

Neuroimaging in human MDMA (Ecstasy) users: A cortical model

Science.gov (United States)

Cowan, Ronald L; Roberts, Deanne M; Joers, James M

2009-01-01

MDMA (3,4 methylenedioxymethamphetamine) has been used by millions of people worldwide as a recreational drug. MDMA and Ecstasy are often used synonymously but it is important to note that the purity of Ecstasy sold as MDMA is not certain. MDMA use is of public health concern, not so much because MDMA produces a common or severe dependence syndrome, but rather because rodent and non-human primate studies have indicated that MDMA (when administered at certain dosages and intervals) can cause long-lasting reductions in markers of brain serotonin (5-HT) that appear specific to fine diameter axons arising largely from the dorsal raphe nucleus (DR). Given the popularity of MDMA, the potential for the drug to produce long-lasting or permanent 5-HT axon damage or loss, and the widespread role of 5-HT function in the brain, there is a great need for a better understanding of brain function in human users of this drug. To this end, neuropsychological, neuroendocrine, and neuroimaging studies have all suggested that human MDMA users may have long-lasting changes in brain function consistent with 5-HT toxicity. Data from animal models leads to testable hypotheses regarding MDMA effects on the human brain. Because neuropsychological and neuroimaging findings have focused on the neocortex, a cortical model is developed to provide context for designing and interpreting neuroimaging studies in MDMA users. Aspects of the model are supported by the available neuroimaging data but there are controversial findings in some areas and most findings have not been replicated across different laboratories and using different modalities. This paper reviews existing findings in the context of a cortical model and suggests directions for future research. PMID:18991874

Behaviour of solitary adult Scandinavian brown bears (Ursus arctos when approached by humans on foot.

Directory of Open Access Journals (Sweden)

Gro Kvelprud Moen

Full Text Available Successful management has brought the Scandinavian brown bear (Ursus arctos L. back from the brink of extinction, but as the population grows and expands the probability of bear-human encounters increases. More people express concerns about spending time in the forest, because of the possibility of encountering bears, and acceptance for the bear is decreasing. In this context, reliable information about the bear's normal behaviour during bear-human encounters is important. Here we describe the behaviour of brown bears when encountering humans on foot. During 2006-2009, we approached 30 adult (21 females, 9 males GPS-collared bears 169 times during midday, using 1-minute positioning before, during and after the approach. Observer movements were registered with a handheld GPS. The approaches started 869±348 m from the bears, with the wind towards the bear when passing it at approximately 50 m. The bears were detected in 15% of the approaches, and none of the bears displayed any aggressive behaviour. Most bears (80% left the initial site during the approach, going away from the observers, whereas some remained at the initial site after being approached (20%. Young bears left more often than older bears, possibly due to differences in experience, but the difference between ages decreased during the berry season compared to the pre-berry season. The flight initiation distance was longer for active bears (115±94 m than passive bears (69±47 m, and was further affected by horizontal vegetation cover and the bear's age. Our findings show that bears try to avoid confrontations with humans on foot, and support the conclusions of earlier studies that the Scandinavian brown bear is normally not aggressive during encounters with humans.

Adult Tobacco Consumption In The U.S., 2000-Present

Data.gov (United States)

U.S. Department of Health & Human Services — 2000 to Present. Adult Tobacco Consumption in the U.S. This dataset highlights critical trends in adult total and per capita consumption of both combustible...

Impact of experimental human pneumococcal carriage on nasopharyngeal bacterial densities in healthy adults.

Science.gov (United States)

Shak, Joshua R; Cremers, Amelieke J H; Gritzfeld, Jenna F; de Jonge, Marien I; Hermans, Peter W M; Vidal, Jorge E; Klugman, Keith P; Gordon, Stephen B

2014-01-01

Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis. To better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative PCR to examine bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after controlled inoculation of healthy human adults with S. pneumoniae serotype 6B. Overall, 33 (63%) of subjects carried S. pneumoniae post-inoculation. The baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis were not statistically associated with likelihood of successful pneumococcal colonization at this study's sample size, although a lower rate of pneumococcal colonization in the presence of S. aureus (7/14) was seen compared to that in the presence of H. influenzae (12/16). Among subjects colonized with pneumococci, the number also carrying either H. influenzae or S. aureus fell during the study and at 14 days post-inoculation, the proportion carrying S. aureus was significantly lower among those who were colonized with S. pneumoniae (p = 0.008) compared to non-colonized subjects. These data on bacterial associations are the first to be reported surrounding experimental human pneumococcal colonization and show that co-colonizing effects are likely subtle rather than absolute.

Clinical grade adult stem cell banking.

Science.gov (United States)

Thirumala, Sreedhar; Goebel, W Scott; Woods, Erik J

2009-07-01

There has been a great deal of scientific interest recently generated by the potential therapeutic applications of adult stem cells in human care but there are several challenges regarding quality and safety in clinical applications and a number of these challenges relate to the processing and banking of these cells ex-vivo. As the number of clinical trials and the variety of adult cells used in regenerative therapy increases, safety remains a primary concern. This has inspired many nations to formulate guidelines and standards for the quality of stem cell collection, processing, testing, banking, packaging and distribution. Clinically applicable cryopreservation and banking of adult stem cells offers unique opportunities to advance the potential uses and widespread implementation of these cells in clinical applications. Most current cryopreservation protocols include animal serum proteins and potentially toxic cryoprotectant additives (CPAs) that prevent direct use of these cells in human therapeutic applications. Long term cryopreservation of adult stem cells under good manufacturing conditions using animal product free solutions is critical to the widespread clinical implementation of ex-vivo adult stem cell therapies. Furthermore, to avoid any potential cryoprotectant related complications, reduced CPA concentrations and efficient post-thaw washing to remove CPA are also desirable. The present review focuses on the current strategies and important aspects of adult stem cell banking for clinical applications. These include current good manufacturing practices (cGMPs), animal protein free freezing solutions, cryoprotectants, freezing & thawing protocols, viability assays, packaging and distribution. The importance and benefits of banking clinical grade adult stem cells are also discussed.

Comparative effects of red and white grapes on oxidative markers and lipidemic parameters in adult hypercholesterolemic humans.

Science.gov (United States)

Rahbar, Ali Reza; Mahmoudabadi, Mohammad Mehdi Shakouri; Islam, Md Shahidul

2015-06-01

The present study compared the effects of consuming red versus white whole grapes on oxidative and lipidemic indices in people with hypercholesterolemia. Sixty nine patients were randomized into three groups. The two treatment groups consumed 500 g of either Condori red grapes or Shahroodi white grapes daily for 8 weeks, and the third group served as a control. Plasma glucose, triacylglycerol (TG), cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) were determined by colorimetric methods at baseline and at the end of the study. In addition, the polyphenol and fiber content of the two grape varieties was measured. TBARS was reduced in both study groups compared to the control group, and the reduction was greater in the group that consumed red grapes compared to the white grapes. TAC was increased significantly in both red and white grape consuming groups compared to the control group. Total cholesterol and LDL-C were decreased in the red grape group compared to the control group. No significant changes in fasting blood glucose, TG or HDL-C were observed among the groups. The results of this study suggest that consumption of the whole fruit of red grapes has more potent anti-oxidative and hypolipidemic effects compared to the white grapes in hyperlipidemic adult humans. Hence, the whole fruit of red grapes may be an excellent fruit choice not only to prevent oxidative stress related metabolic disorders but also cholesterol related cardiovascular diseases, particularly in hyperlipidemic adult humans.

Adult Education in Museums and Public Libraries.

Science.gov (United States)

Miller, Harry G.

Both museums and public libraries are available sources of education for adults. Besides their traditional functions of collecting and preserving items from human artistic or scientific history, museums have taken on a more active role in educating the public, particularly adults. Some educational services provided by museums are dioramas, period…

Human rotavirus group a serotypes causing gastroenteritis in children less than 5 years and HIV-infected adults in Viwandani slum, Nairobi.

Science.gov (United States)

Raini, S K; Nyangao, J; Kombich, J; Sang, C; Gikonyo, J; Ongus, J R; Odari, E O

2015-01-01

Rotavirus remains a leading cause of acute gastroenteritis in children worldwide with an estimated 2000 deaths each day in developing countries. Due to HIV/AIDS scourge in Kenya, it is possible that rotavirus-related gastroenteritis has been aggravated in adults. The Global Alliance for Immunizations has ranked rotavirus infection a priority for vaccine, and, to ensure its success, there is a need to document the local strain(s) circulating in different regions. A cross-sectional study was conducted to document human rotavirus group A serotypes in children below 5 years and HIV-infected adults in Viwandani slum in Nairobi, Kenya. A total of 260 (128 from children and 132 from HIV infected adults) fecal specimen samples were analyzed from August 2012 to July 2013. Screening for rotavirus was done by antigen based enzyme immune-sorbent assay (ELISA), Polyacrylamide gel electrophoresis (PAGE) was used to detect rotavirus electropherotypes and finally genotyping was done by RT-PCR using genotype-specific primer sets targeting VP4 and VP7 genes. Rotavirus was detected in 23% and 8% of children and adult, respectively. Prevalence was high in children of 48 years. Long electropherotypes accounted for 80% and 60% while short electropherotypes accounted for 20% and 40% in children and adult, respectively. The common globally distributed strains, G1 and G3, accounted for 60% detections while the unusual G9 strain accounted for 80% infection in adults. G1P[8] was the common genotypic combination in children, accounting for 40% infection, whereas G9 [P8] accounted for 60% of the infections in adults. This study shows the existence of strain diversity between rotavirus circulating in children and adults within this study group. It further shows that as currently constituted, the 2 vaccines recommended for rotavirus would cover the circulating strain in Viwandani slum. Finally, there is a need for continuous rotavirus strain surveillance in children and a further focus on HIV

[Detection and Analysis of Human Parainfluenza Virus Infection in Hospitalized Adults with Acute Respiratory Tract Infections].

Science.gov (United States)

Li, Xing-Qiao; Liu, Xue-Wei; Zhou, Tao; Pei, Xiao-Fang

2017-11-01

To investigate the prevalence and gene characteristics of different groups of human parainfluenza virus (HPIV) infection in hospitalized adults with acute respiratory tract infections (ARI). RT-PCR was used to detect HPIV hemagglutinin (HA) DNA,which was extracted from sputum samples of 1 039 adult patients with ARI from March,2014 to June,2016. The HA gene amplified from randomly selected positive samples were sequenced to analyze the homology and variation. 10.6% (110/1 039) of these samples were positive for HPIV,including 8 cases of HPIV-1,22 cases of HPIV-2,46 cases of HPIV-3 and 34 cases of HPIV-4. Detectable rate varied among different groups of HPIV according to seasons of the year and ages of patients. No significant differences were found between the positive samples and the reference sequences. Compared with different reference strains of different regions,the genetic distance of nucleotide is the smallest between the strains tested in this study and the reference strains of other provinces and cities in China. In Chengdu region,HPIV virus is highly detected in ARI,all subtypes were detected with HPIV-3 being the main subtype.

A Comparative Analysis of Perinatal Development of Barrel Cortex in Rat, Mouse and Guinea Pig Using Acetylcholinesterase Histochemistry

OpenAIRE

ŞENDEMİR, Erdoğan

2014-01-01

The role of acetylcholinesterase (AChE) in the developing neocortex was reexamined by comparing its expression in rats, mice and guinea pigs, following the protocol for acetylcholinesterase histochemistry (described in Sendemir et al., 1996) in order to determine the suitability of the breeding colony at UludaÛ University for use as an animal model. A total of 103 pups as well as two adult animals of each species were used. In the rat pups, acetylcholinesterase-rich patches were d...

Preferences for technology versus human assistance and control over technology in the performance of kitchen and personal care tasks in baby boomers and older adults.

Science.gov (United States)

Beach, Scott R; Schulz, Richard; Matthews, Judith T; Courtney, Karen; Dabbs, Annette DeVito

2014-11-01

Quality of Life technology (QoLT) stresses humans and technology as mutually dependent and aware, working together to improve task performance and quality of life. This study examines preferences for technology versus human assistance and control in the context of QoLT. Data are from a nationally representative, cross-sectional web-based sample of 416 US baby boomers (45-64) and 114 older adults (65+) on preferences for technology versus human assistance and control in the performance of kitchen and personal care tasks. Multinomial logistic regression and ordinary least squares regression were used to determine predictors of these preferences. Respondents were generally accepting of technology assistance but wanted to maintain control over its' operation. Baby boomers were more likely to prefer technology than older adults, and those with fewer QoLT privacy concerns and who thought they were more likely to need future help were more likely to prefer technology over human assistance and more willing to relinquish control to technology. Results suggest the need for design of person- and context-aware QoLT systems that are responsive to user desires for level of control over operation of the technology. The predictors of these preferences suggest potentially receptive markets for the targeting of QoLT systems.

Adult Continuing Education and Human Resource Development: Present Competitors, Potential Partners

Science.gov (United States)

Smith, Douglas H.

2013-01-01

"Author's Note": In May 1989, this article was published in "Livelong Learning," the monthly practitioner journal of the American Association for Adult and Continuing Education (Vol. 12, No. 7, pp. 13-17). Now viewed as a period reference article, it presents the relationship of adult and continuing education (ACE) and…

Chromosome 11-linked determinant controls fetal globin expression and the fetal-to-adult globin switch

International Nuclear Information System (INIS)

Melis, M.; Demopulos, G.; Najfeld, V.; Zhang, J.W.; Brice, M.; Papayannopoulou, T.; Stamatoyannopoulos, G.

1987-01-01

Hybrids formed by fusing mouse erythroleukemia (MEL) cells with human fetal erythroid cells produce human fetal globin, but they switch to adult globin production as culture time advances. To obtain information on the chromosomal assignment of the elements that control γ-to-β switching, the authors analyzed the chromosomal composition of hybrids producing exclusively or predominantly human fetal globin and hybrids producing only adult human globin. No human chromosome was consistently present in hybrids expressing fetal globin and consistently absent in hybrids expressing adult globin. Subcloning experiments demonstrated identical chromosomal compositions in subclones displaying the fetal globin program and those that had switched to expression of the adult globin program. These data indicate that retention of only one human chromosome -- i.e., chromosome 11 -- is sufficient for expression of human fetal globin and the subsequent γ-to-β switch. The results suggest that the γ-to-β switch is controlled either cis to the β-globin locus of by a trans-acting mechanism, the genes of which reside on human chromosome 11

In vitro and in vivo characterisation of nor-β-CIT: a potential radioligand for visualisation of the serotonin transporter in the brain

International Nuclear Information System (INIS)

Bergstroem, K.A.; Halldin, C.; Hall, H.; Lundkvist, C.; Ginovart, N.; Swahn, C.G.; Farde, L.

1997-01-01

Radiolabelled 2β-carbomethoxy-3β-(4-iodophenyl)tropane (β-CIT) has been used in clinical studies for the imaging of dopamine and serotonin transporters with single-photon emission tomography (SPET). 2β-Carbomethoxy-3β-(4-iodophenyl)nortropane (nor-β-CIT) is a des-methyl analogue of β-CIT, which in vitro has tenfold higher affinity (IC 50 =0.36 nM) to the serotonin transporter than β-CIT (IC 50 =4.2 nM). Nor-β-CIT may thus be a useful radioligand for imaging of the serotonin transporter. In the present study iodine-125 and carbon-11 labelled nor-β-CIT were prepared for in vitro autoradiographic studies on post-mortem human brain cryosections and for in vivo positron emission tomography (PET) studies in Cynomolgus monkeys. Whole hemisphere autoradiography with [ 125 I[nor-β-CIT demonstrated high binding in the striatum, the thalamus and cortical regions of the human brain. Addition of a high concentration (1 μM) of citalopram inhibited binding in the thalamus and the neocortex, but not in the striatum. In PET studies with [ 11 C[nor-β-CIT there was rapid uptake of radioactivity in the monkey brain (6% of injected dose at 15 min) and high accumulation of radioactivity in the striatum, thalamus and neocortex. Thalamus to cerebellum and cortex to cerebellum ratios were 2.5 and 1.8 at 60 min, respectively. The ratios obtained with [ 11 C[nor-β-CIT were 20%-40% higher than those previously obtained with [ 11 C[β-CIT. Radioactivity in the thalamus and the neocortex but not in the striatum was displaceable with citalopram (5 mg/kg). In conclusion, nor-β-CIT binds to the serotonin transporter in the primate brain in vitro and in vivo and has potential for PET and SPET imaging of the serotonin transporter in human brain. (orig.). With 4 figs

Early developmental gene enhancers affect subcortical volumes in the adult human brain.

Science.gov (United States)

Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

2016-05-01

Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

From tetrapods to primates: conserved developmental mechanisms in diverging ecological adaptations.

Science.gov (United States)

Aboitiz, Francisco; Montiel, Juan F

2012-01-01

Primates are endowed with a brain about twice the size that of a mammal with the same body size, and humans have the largest brain relative to body size of all animals. This increase in brain size may be related to the acquisition of higher cognitive skills that permitted more complex social interactions, the evolution of culture, and the eventual ability to manipulate the environment. Nevertheless, in its internal structure, the primate brain shares a very conserved design with other mammals, being covered by a six-layered neocortex that, although expands disproportionately to other brain components, it does so following relatively well-defined allometric trends. Thus, the most fundamental events generating the basic design of the primate and human brain took place before the appearance of the first primate-like animal. Presumably, the earliest mammals already displayed a brain morphology radically different from that of their ancestors and that of their sister group, the reptiles, being characterized by the presence of an incipient neocortex that underwent an explosive growth in subsequent mammal evolution. In this chapter, we propose an integrative hypothesis for the origin of the mammalian neocortex, by considering the developmental modifications, functional networks, and ecological adaptations involved in the generation of this structure during the cretaceous period. Subsequently, the expansion of the primate brain is proposed to have relied on the amplification of the same, or very similar, developmental mechanisms as those involved in its primary origins, even in different ecological settings. Copyright © 2012 Elsevier B.V. All rights reserved.

The History of Adult Education in Greece.

Science.gov (United States)

Boucouvalas, Marcie

Adult education in Greece dates back to the time of Homer. Poetry and Panhellenic festivals were the earliest forms of adult education in Greece. By classical times, however, an entire learning society of human and material resources had been developed. Greek society experienced periods of high levels of culture and learning only to be conquered…

Oral Human Papillomavirus Detection in Older Adults Who Have Human Immunodeficiency Virus Infection

Science.gov (United States)

Fatahzadeh, Mahnaz; Schlecht, Nicolas F.; Chen, Zigui; Bottalico, Danielle; McKinney, Sharod; Ostoloza, Janae; Dunne, Anne; Burk, Robert D.

2014-01-01

Objective To evaluate reproducibility of oral rinse self-collection for HPV detection and investigate associations between oral HPV, oral lesions, immune and sociodemographic factors, we performed a cross-sectional study of older adults with HIV infection. Study Design We collected oral rinse samples from 52 subjects at two different times of day followed by an oral examination and interview. We identified HPV using PCR platforms optimized for detection of mucosal and cutaneous types. Results Eighty seven percent of individuals had oral HPV, of which 23% had oncogenic alpha, 40% had non-oncogenic alpha, and 46% had beta or gamma HPV. Paired oral specimens were concordant in all parameters tested. Significant associations observed for oral HPV with increased HIV viral load, hepatitis-C seropositivity, history of sexually transmitted diseases and lifetime number of sexual partners. Conclusions Oral cavity may be a reservoir of subclinical HPV in older adults who have HIV infection. Understanding natural history, transmission and potential implications of oral HPV warrants further investigations. PMID:23375488

Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in healthy adults

OpenAIRE

Gaudinski, Martin R.; Coates, Emily E.; Houser, Katherine V.; Chen, Grace L.; Yamshchikov, Galina; Saunders, Jamie G.; Holman, LaSonji A.; Gordon, Ingelise; Plummer, Sarah; Hendel, Cynthia S.; Conan-Cibotti, Michelle; Lorenzo, Margarita Gomez; Sitar, Sandra; Carlton, Kevin; Laurencot, Carolyn

2018-01-01

Background VRC01 is a human broadly neutralizing monoclonal antibody (bnMAb) against the CD4-binding site of the HIV-1 envelope glycoprotein (Env) that is currently being evaluated in a Phase IIb adult HIV-1 prevention efficacy trial. VRC01LS is a modified version of VRC01, designed for extended serum half-life by increased binding affinity to the neonatal Fc receptor. Methods and findings This Phase I dose-escalation study of VRC01LS in HIV-negative healthy adults was conducted by the Vaccin...

Cellular and synaptic localization of EAAT2a in human cerebral cortex

Directory of Open Access Journals (Sweden)

Marcello eMelone

2011-01-01

Full Text Available We used light and electron microscopic immunocytochemical techniques to analyze the distribution, cellular and synaptic localization of EAAT2, the main glutamate transporter, in normal human neocortex. EAAT2a immunoreactivity was in all layers and consisted of small neuropilar puncta and rare cells. In white matter EAAT2a+ cells were numerous. Electron microscopic studies showed that in gray matter ∼77% of immunoreactive elements were astrocytic processes, ∼14% axon terminals, ∼2.8% dendrites, whereas ∼5% were unidentifiable. In white matter, ∼81% were astrocytic processes, ∼17% were myelinated axons and ∼2.0% were unidentified. EAAT2a immunoreactivity was never in microglial cells and oligodendrocytes. Pre-embedding electron microscopy showed that ∼67% of EAAT2a expressed at (or in the vicinity of asymmetric synapses was in astrocytes, ∼17% in axon terminals, while ∼13% was both in astrocytes and in axons. Post-embeddeding electron microscopy studies showed that in astrocytic processes contacting asymmetric synapses and in axon terminals, gold particle density was ∼25.1 and ∼2.8 particles/µm2, respectively, and was concentrated in a membrane region extending for ∼300 nm from the active zone edge. Besides representing the first detailed description of EAAT2a in human cerebral cortex, these findings may contribute to understanding its role in the pathophysiology of neuropsychiatric diseases.

Cholinergic Modulation of Cortical Microcircuits Is Layer-Specific: Evidence from Rodent, Monkey and Human Brain

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Joshua Obermayer

2017-12-01

Full Text Available Acetylcholine (ACh signaling shapes neuronal circuit development and underlies specific aspects of cognitive functions and behaviors, including attention, learning, memory and motivation. During behavior, activation of muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs by ACh alters the activation state of neurons, and neuronal circuits most likely process information differently with elevated levels of ACh. In several brain regions, ACh has been shown to alter synaptic strength as well. By changing the rules for synaptic plasticity, ACh can have prolonged effects on and rearrange connectivity between neurons that outlasts its presence. From recent discoveries in the mouse, rat, monkey and human brain, a picture emerges in which the basal forebrain (BF cholinergic system targets the neocortex with much more spatial and temporal detail than previously considered. Fast cholinergic synapses acting on a millisecond time scale are abundant in the mammalian cerebral cortex, and provide BF cholinergic neurons with the possibility to rapidly alter information flow in cortical microcircuits. Finally, recent studies have outlined novel mechanisms of how cholinergic projections from the BF affect synaptic strength in several brain areas of the rodent brain, with behavioral consequences. This review highlights these exciting developments and discusses how these findings translate to human brain circuitries.

Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma.

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Lee Ratner

Full Text Available Human T-cell leukemia virus-associated adult T-cell leukemia-lymphoma (ATLL has a very poor prognosis, despite trials of a variety of different treatment regimens. Virus expression has been reported to be limited or absent when ATLL is diagnosed, and this has suggested that secondary genetic or epigenetic changes are important in disease pathogenesis.We prospectively investigated combination chemotherapy followed by antiretroviral therapy for this disorder. Nineteen patients were prospectively enrolled between 2002 and 2006 at five medical centers in a phase II clinical trial of infusional chemotherapy with etoposide, doxorubicin, and vincristine, daily prednisone, and bolus cyclophosphamide (EPOCH given for two to six cycles until maximal clinical response, and followed by antiviral therapy with daily zidovudine, lamivudine, and alpha interferon-2a for up to one year. Seven patients were on study for less than one month due to progressive disease or chemotherapy toxicity. Eleven patients achieved an objective response with median duration of response of thirteen months, and two complete remissions. During chemotherapy induction, viral RNA expression increased (median 190-fold, and virus replication occurred, coincident with development of disease progression.EPOCH chemotherapy followed by antiretroviral therapy is an active therapeutic regimen for adult T-cell leukemia-lymphoma, but viral reactivation during induction chemotherapy may contribute to treatment failure. Alternative therapies are sorely needed in this disease that simultaneously prevent virus expression, and are cytocidal for malignant cells.

Retention and relearning of spatial delayed alternation in rats after ablation of the prefrontal or total non-prefrontal isocortex

DEFF Research Database (Denmark)

Wörtwein, Gitta; Mogensen, Jesper; Divac, Ivan

1994-01-01

Neurobiologi, præfrontal cortex, delayed alternation, funktionel genopretning, neocortex, rotte......Neurobiologi, præfrontal cortex, delayed alternation, funktionel genopretning, neocortex, rotte...

Sex stereotypes influence adults' perception of babies' cries

OpenAIRE

Reby, David; Levréro, Florence; Gustafsson, Erik; Mathevon, Nicolas

2016-01-01

Background Despite widespread evidence that gender stereotypes influence human parental behavior, their potential effects on adults? perception of babies? cries have been overlooked. In particular, whether adult listeners overgeneralize the sex dimorphism that characterizes the voice of adult speakers (men are lower-pitched than women) to their perception of babies? cries has not been investigated. Methods We used playback experiments combining natural and re-synthesised cries of 3?month-old ...

Circadian oscillators in the mouse brain

DEFF Research Database (Denmark)

Rath, Martin F; Rovsing, Louise; Møller, Morten

2014-01-01

with conditional cell-specific clock gene deletions. This prompted us to analyze the molecular clockwork of the mouse neocortex and cerebellum in detail. Here, by use of in situ hybridization and quantitative RT-PCR, we show that clock genes are expressed in all six layers of the neocortex and the Purkinje...... and granular cell layers of the cerebellar cortex of the mouse brain. Among these, Per1, Per2, Cry1, Arntl, and Nr1d1 exhibit circadian rhythms suggesting that local running circadian oscillators reside within neurons of the mouse neocortex and cerebellar cortex. The temporal expression profiles of clock genes...... are similar in the neocortex and cerebellum, but they are delayed by 5 h as compared to the SCN, suggestively reflecting a master-slave relationship between the SCN and extra-hypothalamic oscillators. Furthermore, ARNTL protein products are detectable in neurons of the mouse neocortex and cerebellum...

Production and organization of neocortical interneurons

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Khadeejah T Sultan

2013-11-01

Full Text Available Inhibitory GABA (γ-aminobutyric acid-ergic interneurons are a vital component of the neocortex responsible for shaping its output through a variety of inhibitions. Consisting of many flavors, interneuron subtypes are predominantly defined by their morphological, physiological, and neurochemical properties that help to determine their functional role within the neocortex. During development, these cells are born in the subpallium where they then tangentially migrate over long distances before being radially positioned to their final location in the cortical laminae. As development progresses into adolescence, these cells mature and form chemical and electrical connections with both glutamatergic excitatory neurons and other interneurons ultimately establishing the cortical network. The production, migration, and organization of these cells are determined by vast array of extrinsic and intrinsic factors that work in concert in order to assemble a proper functioning cortical inhibitory network. Failure of these cells to undergo these processes results in abnormal positioning and cortical function. In humans, this can bring about several neurological disorders including schizophrenia, epilepsy and autism spectrum disorders. In this article, we will review previous literature that has revealed the framework for interneuron neurogenesis and migratory behavior as well as discuss recent findings that aim to elucidate the spatial and functional organization of interneurons within the neocortex.

A Rare Case of Human Coronavirus 229E Associated with Acute Respiratory Distress Syndrome in a Healthy Adult

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Foula Vassilara

2018-01-01

Full Text Available Human coronavirus 229E (HCoV-229E is one of the first coronavirus strains being described. It is linked to common cold symptoms in healthy adults. Younger children and the elderly are considered vulnerable to developing lower respiratory tract infections (LRTIs. In particular, immunocompromised patients have been reported with severe and life-threatening LRTIs attributed to HCoV-229E. We report for the first time a case of LRTI and acute respiratory distress syndrome developed in a healthy adult with no comorbidities and HCoV-229E strain identified as the only causative agent. A 45-year-old female with a clear medical history presented with fever, cough, and headache. Respiratory tract infection was diagnosed, and empirical antibiotics were started. Within two days, she developed bilateral pleural effusions, diffuse consolidations, and ground glass opacities involving all lung fields. She needed immediate oxygen supply, while ABGs deteriorated and chest imaging and PaO2/FiO2 indicated ARDS. Early administration of systemic corticosteroids led to gradual clinical improvement. Multiplex PCR from nasal secretions was positive only for HCoV-229E and negative for multiple other pathogens. It remains to be elucidated how an immunocompetent adult developed a life-threatening LRTI caused by a “benign considered” coronavirus strain, the HCoV-229E.

Assessment of human papilloma virus infection in adult laryngeal papilloma using a screening test.

Science.gov (United States)

Makiyama, Kiyoshi; Hirai, Ryoji; Matsuzaki, Hiroumi; Ikeda, Minoru

2013-03-01

Human papilloma virus (HPV) infection is involved in both juvenile and adult laryngeal papilloma. We wished to determine which types of adult laryngeal papilloma were clinically related to HPV infection. We hypothesized that multiple-site and recurrent papillomas would have a strong relationship to HPV and conducted the present study to test this hypothesis. Thirteen male patients with adult laryngeal papilloma who underwent resection of papilloma between August 2006 and September 2009 were studied. We examined the relationships between whether the tumor was solitary or multiple, presence or absence of recurrence after surgery, and HPV infection. High-risk HPV types (HPV-DNA types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) and low-risk HPV types (6, 11, 42, 43, and 44) were tested by a liquid-phase hybridization method. In addition, HPV typing was performed for patients positive for low-risk HPV types. Twenty patients with laryngeal carcinoma or laryngeal leukoplakia were enrolled as the control group. In the laryngeal papilloma group, all patients tested were negative for high-risk HPV and 69.2% were positive for low-risk HPV. Typing performed for seven of the patients who tested positive for low-risk HPV showed that one patient was positive for HPV-11, whereas the remaining six patients were positive for HPV-6. All patients with recurrent laryngeal papillomatosis (RLP) were positive for low-risk HPV. All patients who were positive for low-risk HPV had RLP. Tumor samples from repeat operations were positive for low-risk HPV in all patients tested. HPV was not detected in the control group. The relationship between RLP and low-risk HPV was strong, with all cases that were positive for low-risk HPV showing recurrence. Tumor tissue resected at the time of repeat surgery was positive for low-risk HPV in all cases tested. Copyright © 2013 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

FASH and MASH: female and male adult human phantoms based on polygon mesh surfaces: II. Dosimetric calculations

Energy Technology Data Exchange (ETDEWEB)

Kramer, R; Cassola, V F; Khoury, H J [Department of Nuclear Energy, Federal University of Pernambuco, Avenida Prof. Luiz Freire, 1000, CEP 50740-540, Recife (Brazil); Vieira, J W [Federal Institute of Education, Science and Technology of Pernambuco, Recife (Brazil); De Melo Lima, V J [Department of Anatomy, Federal University of Pernambuco, Recife (Brazil); Robson Brown, K [Imaging Laboratory, Department of Archaeology and Anthropology, University of Bristol, Bristol (United Kingdom)], E-mail: rkramer@uol.com.br

2010-01-07

Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been developed in the first part of this study using 3D animation software and anatomical atlases to replace the image-based FAX06 and the MAX06 voxel phantoms. 3D modelling methods allow for phantom development independent from medical images of patients, volunteers or cadavers. The second part of this study investigates the dosimetric implications for organ and tissue equivalent doses due to the anatomical differences between the new and the old phantoms. These differences are mainly caused by the supine position of human bodies during scanning in order to acquire digital images for voxel phantom development. Compared to an upright standing person, in image-based voxel phantoms organs are often coronally shifted towards the head and sometimes the sagittal diameter of the trunk is reduced by a gravitational change of the fat distribution. In addition, volumes of adipose and muscle tissue shielding internal organs are sometimes too small, because adaptation of organ volumes to ICRP-based organ masses often occurs at the expense of general soft tissues, such as adipose, muscle or unspecified soft tissue. These effects have dosimetric consequences, especially for partial body exposure, such as in x-ray diagnosis, but also for whole body external exposure and for internal exposure. Using the EGSnrc Monte Carlo code, internal and external exposure to photons and electrons has been simulated with both pairs of phantoms. The results show differences between organ and tissue equivalent doses for the upright standing FASH/MASH and the image-based supine FAX06/MAX06 phantoms of up to 80% for external exposure and up to 100% for internal exposure. Similar differences were found for external exposure between FASH/MASH and REGINA/REX, the reference voxel phantoms of the International Commission on Radiological Protection. Comparison of effective doses for external photon

FASH and MASH: female and male adult human phantoms based on polygon mesh surfaces: II. Dosimetric calculations

Science.gov (United States)

Kramer, R.; Cassola, V. F.; Khoury, H. J.; Vieira, J. W.; de Melo Lima, V. J.; Robson Brown, K.

2010-01-01

Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been developed in the first part of this study using 3D animation software and anatomical atlases to replace the image-based FAX06 and the MAX06 voxel phantoms. 3D modelling methods allow for phantom development independent from medical images of patients, volunteers or cadavers. The second part of this study investigates the dosimetric implications for organ and tissue equivalent doses due to the anatomical differences between the new and the old phantoms. These differences are mainly caused by the supine position of human bodies during scanning in order to acquire digital images for voxel phantom development. Compared to an upright standing person, in image-based voxel phantoms organs are often coronally shifted towards the head and sometimes the sagittal diameter of the trunk is reduced by a gravitational change of the fat distribution. In addition, volumes of adipose and muscle tissue shielding internal organs are sometimes too small, because adaptation of organ volumes to ICRP-based organ masses often occurs at the expense of general soft tissues, such as adipose, muscle or unspecified soft tissue. These effects have dosimetric consequences, especially for partial body exposure, such as in x-ray diagnosis, but also for whole body external exposure and for internal exposure. Using the EGSnrc Monte Carlo code, internal and external exposure to photons and electrons has been simulated with both pairs of phantoms. The results show differences between organ and tissue equivalent doses for the upright standing FASH/MASH and the image-based supine FAX06/MAX06 phantoms of up to 80% for external exposure and up to 100% for internal exposure. Similar differences were found for external exposure between FASH/MASH and REGINA/REX, the reference voxel phantoms of the International Commission on Radiological Protection. Comparison of effective doses for external photon

National Adult Tobacco Survey (NATS)

Data.gov (United States)

U.S. Department of Health & Human Services — 2013-2014. The National Adult Tobacco Survey (NATS) was created to assess the prevalence of tobacco use, as well as the factors promoting and impeding tobacco use...

Early development of synchrony in cortical activations in the human.

Science.gov (United States)

Koolen, N; Dereymaeker, A; Räsänen, O; Jansen, K; Vervisch, J; Matic, V; Naulaers, G; De Vos, M; Van Huffel, S; Vanhatalo, S

2016-05-13

Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Impact of experimental human pneumococcal carriage on nasopharyngeal bacterial densities in healthy adults.

Directory of Open Access Journals (Sweden)

Joshua R Shak

Full Text Available Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis. To better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative PCR to examine bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after controlled inoculation of healthy human adults with S. pneumoniae serotype 6B. Overall, 33 (63% of subjects carried S. pneumoniae post-inoculation. The baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis were not statistically associated with likelihood of successful pneumococcal colonization at this study's sample size, although a lower rate of pneumococcal colonization in the presence of S. aureus (7/14 was seen compared to that in the presence of H. influenzae (12/16. Among subjects colonized with pneumococci, the number also carrying either H. influenzae or S. aureus fell during the study and at 14 days post-inoculation, the proportion carrying S. aureus was significantly lower among those who were colonized with S. pneumoniae (p = 0.008 compared to non-colonized subjects. These data on bacterial associations are the first to be reported surrounding experimental human pneumococcal colonization and show that co-colonizing effects are likely subtle rather than absolute.

Proteolytic activity in the adult and larval stages of the human roundworm parasite Angiostrongylus costaricensis

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Karina Mastropasqua Rebello

2012-09-01

Full Text Available Angiostrongylus costaricensis is a nematode that causes abdominal angiostrongyliasis, a widespread human parasitism in Latin America. This study aimed to characterize the protease profiles of different developmental stages of this helminth. First-stage larvae (L1 were obtained from the faeces of infected Sigmodon hispidus rodents and third-stage larvae (L3 were collected from mollusks Biomphalaria glabrata previously infected with L1. Adult worms were recovered from rodent mesenteric arteries. Protein extraction was performed after repeated freeze-thaw cycles followed by maceration of the nematodes in 40 mM Tris base. Proteolysis of gelatin was observed by zymography and found only in the larval stages. In L3, the gelatinolytic activity was effectively inhibited by orthophenanthroline, indicating the involvement of metalloproteases. The mechanistic class of the gelatinases from L1 could not be precisely determined using traditional class-specific inhibitors. Adult worm extracts were able to hydrolyze haemoglobin in solution, although no activity was observed by zymography. This haemoglobinolytic activity was ascribed to aspartic proteases following its effective inhibition by pepstatin, which also inhibited the haemoglobinolytic activity of L1 and L3 extracts. The characterization of protease expression throughout the A. costaricensis life cycle may reveal key factors influencing the process of parasitic infection and thus foster our understanding of the disease pathogenesis.

Developmental trajectory of time perspective: From children to older adults.

Science.gov (United States)

Chen, Tao; Liu, Lu-Lu; Cui, Ji-Fang; Chen, Xing-Jie; Wang, Ya

2016-12-01

Time perspective is a fundamental dimension of the psychological time construct, with a pervasive and powerful influence on human behavior. However, the developmental trajectory of time perspective across a human lifespan remains unclear. The current study aimed to portray the developmental trajectory of all dimensions of time perspectives from children to older adults in a large sample. A total of 1,901 individuals (aged 9-84 years) completed measures of time perspective. They were then divided into five age groups: children, teenagers, young adults, middle-aged adults, and older adults. Results suggested that each time perspective showed a unique developmental pattern across the lifespan. Moreover, perceived economic situation and education were related to some dimensions of time perspective. © 2016 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

Therapeutic potential of adult stem cells

DEFF Research Database (Denmark)

Serakinci, Nedime; Keith, W. Nicol

2006-01-01

is the necessity to be able to identify, select, expand and manipulate cells outside the body. Recent advances in adult stem cell technologies and basic biology have accelerated therapeutic opportunities aimed at eventual clinical applications. Adult stem cells with the ability to differentiate down multiple...... lineages are an attractive alternative to human embryonic stem cells (hES) in regenerative medicine. In many countries, present legislation surrounding hES cells makes their use problematic, and indeed the origin of hES cells may represent a controversial issue for many communities. However, adult stem...... cells are not subject to these issues. This review will therefore focus on adult stem cells. Based on their extensive differentiation potential and, in some cases, the relative ease of their isolation, adult stem cells are appropriate for clinical development. Recently, several observations suggest...

Differential oxidative stress induced by dengue virus in monocytes from human neonates, adult and elderly individuals.

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Nereida Valero

Full Text Available Changes in immune response during lifespan of man are well known. These changes involve decreased neonatal and elderly immune response. In addition, it has been shown a relationship between immune and oxidative mechanisms, suggesting that altered immune response could be associated to altered oxidative response. Increased expression of nitric oxide (NO has been documented in dengue and in monocyte cultures infected with different types of dengue virus. However, there is no information about the age-dependent NO oxidative response in humans infected by dengue virus. In this study, monocyte cultures from neonatal, elderly and adult individuals (n = 10 each group were infected with different dengue virus types (DENV- 1 to 4 and oxidative/antioxidative responses and apoptosis were measured at days 1 and 3 of culture. Increased production of NO, lipid peroxidation and enzymatic and nonenzymatic anti-oxidative responses in dengue infected monocyte cultures were observed. However, neonatal and elderly monocytes had lower values of studied parameters when compared to those in adult-derived cultures. Apoptosis was present in infected monocytes with higher values at day 3 of culture. This reduced oxidant/antioxidant response of neonatal and elderly monocytes could be relevant in the pathogenesis of dengue disease.

Neural mechanisms of transient neocortical beta rhythms: Converging evidence from humans, computational modeling, monkeys, and mice

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Sherman, Maxwell A.; Lee, Shane; Law, Robert; Haegens, Saskia; Thorn, Catherine A.; Hämäläinen, Matti S.; Moore, Christopher I.; Jones, Stephanie R.

2016-01-01

Human neocortical 15–29-Hz beta oscillations are strong predictors of perceptual and motor performance. However, the mechanistic origin of beta in vivo is unknown, hindering understanding of its functional role. Combining human magnetoencephalography (MEG), computational modeling, and laminar recordings in animals, we present a new theory that accounts for the origin of spontaneous neocortical beta. In our MEG data, spontaneous beta activity from somatosensory and frontal cortex emerged as noncontinuous beta events typically lasting drive targeting proximal and distal dendrites of pyramidal neurons, where the defining feature of a beta event was a strong distal drive that lasted one beta period (∼50 ms). This beta mechanism rigorously accounted for the beta event profiles; several other mechanisms did not. The spatial location of synaptic drive in the model to supragranular and infragranular layers was critical to the emergence of beta events and led to the prediction that beta events should be associated with a specific laminar current profile. Laminar recordings in somatosensory neocortex from anesthetized mice and awake monkeys supported these predictions, suggesting this beta mechanism is conserved across species and recording modalities. These findings make several predictions about optimal states for perceptual and motor performance and guide causal interventions to modulate beta for optimal function. PMID:27469163

Development of a physiologically based pharmacokinetic model for assessment of human exposure to bisphenol A

International Nuclear Information System (INIS)

Yang, Xiaoxia; Doerge, Daniel R.; Teeguarden, Justin G.; Fisher, Jeffrey W.

2015-01-01

A previously developed physiologically based pharmacokinetic (PBPK) model for bisphenol A (BPA) in adult rhesus monkeys was modified to characterize the pharmacokinetics of BPA and its phase II conjugates in adult humans following oral ingestion. Coupled with in vitro studies on BPA metabolism in the liver and the small intestine, the PBPK model was parameterized using oral pharmacokinetic data with deuterated-BPA (d 6 -BPA) delivered in cookies to adult humans after overnight fasting. The availability of the serum concentration time course of unconjugated d 6 -BPA offered direct empirical evidence for the calibration of BPA model parameters. The recalibrated PBPK adult human model for BPA was then evaluated against published human pharmacokinetic studies with BPA. A hypothesis of decreased oral uptake was needed to account for the reduced peak levels observed in adult humans, where d 6 -BPA was delivered in soup and food was provided prior to BPA ingestion, suggesting the potential impact of dosing vehicles and/or fasting on BPA disposition. With the incorporation of Monte Carlo analysis, the recalibrated adult human model was used to address the inter-individual variability in the internal dose metrics of BPA for the U.S. general population. Model-predicted peak BPA serum levels were in the range of pM, with 95% of human variability falling within an order of magnitude. This recalibrated PBPK model for BPA in adult humans provides a scientific basis for assessing human exposure to BPA that can serve to minimize uncertainties incurred during extrapolations across doses and species. - Highlights: • A PBPK model predicts the kinetics of bisphenol A (BPA) in adult humans. • Serum concentrations of aglycone BPA are available for model calibration. • Model predicted peak BPA serum levels for adult humans were in the range of pM. • Model predicted 95% of human variability fell within an order of magnitude.

Microglia show altered morphology and reduced arborization in human brain during aging and Alzheimer's disease.

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Davies, Danielle S; Ma, Jolande; Jegathees, Thuvarahan; Goldsbury, Claire

2017-11-01

Changes in microglia function are involved in Alzheimer's disease (AD) for which ageing is the major risk factor. We evaluated microglial cell process morphologies and their gray matter coverage (arborized area) during ageing and in the presence and absence of AD pathology in autopsied human neocortex. Microglial cell processes were reduced in length, showed less branching and reduced arborized area with aging (case range 52-98 years). This occurred during normal ageing and without microglia dystrophy or changes in cell density. There was a larger reduction in process length and arborized area in AD compared to aged-matched control microglia. In AD cases, on average, 49%-64% of microglia had discontinuous and/or punctate Iba1 labeled processes instead of continuous Iba1 distribution. Up to 16% of aged-matched control microglia displayed discontinuous or punctate features. There was no change in the density of microglial cell bodies in gray matter during ageing or AD. This demonstrates that human microglia show progressive cell process retraction without cell loss during ageing. Additional changes in microglia occur with AD including Iba1 protein puncta and discontinuity. We suggest that reduced microglial arborized area may be an aging-related correlate of AD in humans. These variations in microglial cells during ageing and in AD could reflect changes in neural-glial interactions which are emerging as key to mechanisms involved in ageing and neurodegenerative disease. © 2016 International Society of Neuropathology.

Nanosized fibers' effect on adult human articular chondrocytes behavior

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Stenhamre, Hanna [Biopolymer Technology, Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg (Sweden); Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg (Sweden); Thorvaldsson, Anna, E-mail: anna.thorvaldsson@swerea.se [Biopolymer Technology, Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg (Sweden); Swerea IVF, Mölndal (Sweden); Enochson, Lars [Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg (Sweden); Walkenström, Pernilla [Swerea IVF, Mölndal (Sweden); Lindahl, Anders [Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg (Sweden); Brittberg, Mats [Cartilage Research Unit, University of Gothenburg, Department Orthopaedics, Kungsbacka Hospital, Kungsbacka (Sweden); Gatenholm, Paul [Biopolymer Technology, Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg (Sweden)

2013-04-01

Tissue engineering with chondrogenic cell based therapies is an expanding field with the intention of treating cartilage defects. It has been suggested that scaffolds used in cartilage tissue engineering influence cellular behavior and thus the long-term clinical outcome. The objective of this study was to assess whether chondrocyte attachment, proliferation and post-expansion re-differentiation could be influenced by the size of the fibers presented to the cells in a scaffold. Polylactic acid (PLA) scaffolds with different fiber morphologies were produced, i.e. microfiber (MS) scaffolds as well as nanofiber-coated microfiber scaffold (NMS). Adult human articular chondrocytes were cultured in the scaffolds in vitro up to 28 days, and the resulting constructs were assessed histologically, immunohistochemically, and biochemically. Attachment of cells and serum proteins to the scaffolds was affected by the architecture. The results point toward nano-patterning onto the microfibers influencing proliferation of the chondrocytes, and the overall 3D environment having a greater influence on the re-differentiation. In the efforts of finding the optimal scaffold for cartilage tissue engineering, studies as the current contribute to the knowledge of how to affect and control chondrocytes behavior. - Highlights: ► Chondrocyte behavior in nanofiber-coated microfiber versus microfiber scaffolds ► High porosity (> 90%) and large pore sizes (a few hundred μm) of nanofibrous scaffolds ► Proliferation enhanced by presence of nanofibers ► Differentiation not significantly affected ► Cell attachment improved in presence of both nanofibers and serum.

The cook, the thief, his wife and her lover: on the evolution of the human reproductive strategy.

Science.gov (United States)

Schuiling, G A

2003-12-01

Human reproductive strategy differs from that of most other mammals, including Apes such as the closely related chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). For example, humans, although basically polygamic, exhibit a strong tendency to (serial) monogamy and--very rare for a mammal--provide biparental care. Moreover, humans are (almost) permanently willing to mate but, in contrast to other species, do so only in private. Unlike chimpanzees and bonobos, the human female exhibits no external signs of ovulation; rather a number of bodily features, e.g. permanently swollen milk glands and the quality of skin and hair, indicate fitness to breed. Human males also exhibit qualities that are rare among mammals: fertile males can be in the company of fertile females without sex being an imperative--although the awareness of sexuality is generally omnipresent. Moreover, unlike most other Apes, human males can cooperate in large groups, in spite of their polygynic inclination and their tendency to compete with each other for access to females. This capacity probably evolved in response to the necessity to acquire food, in particular meat, which was difficult to obtain by a single man. But life in large, complex, multi-male, multi-female groups places great demands on the members' social skills and, to be able to meet these demands, a large, sophisticated brain (neocortex) is needed. Food (and in its wake, cooking) probably forced man to live in ever-larger groups and to evolve the capacity to cooperate. This, in its turn, drove man's present-days psychosocial (emotional and intellectual) make-up. But for this to evolve, an adaptation of reproductive strategy was a conditio sine qua non.

Effect of homologous synovial membrane on adult human articular cartilage in organ culture, and failure to influence it with D-penicillamine.

OpenAIRE

Jacoby, R K

1980-01-01

Adult human articular cartilage has been maintained in organ culture for 8 days, and the culture medium, which was changed on alternate days, was pooled. Normal and rheumatoid cartilage was obtained from patients and 4 types of culture were prepared: (1) cartilage alone; (2) cartilage + D-penicillamine; (3) cartilage + homologous synovium; (4) cartilage, synovium, and D-penicillamine. The hexosamines and hexuronic acid were measured in the cartilage explants and in the medium. The quantity re...

Hippocampal volume is decreased in adults with hypothyroidism.

Science.gov (United States)

Cooke, Gillian E; Mullally, Sinead; Correia, Neuman; O'Mara, Shane M; Gibney, James

2014-03-01

Thyroid hormones are important for the adult brain, particularly regions of the hippocampus including the dentate gyrus and CA1 and CA3 regions. The hippocampus is a thyroid hormone receptor-rich region of the brain involved in learning and memory. Consequently, alterations in thyroid hormone levels have been reported to impair hippocampal-associated learning and memory, synaptic plasticity, and neurogenesis. While these effects have been shown primarily in developing rats, as well as in adult rats, little is known about the effects in adult humans. There are currently no data regarding structural changes in the hippocampus as a result of adult-onset hypothyroidism. We aimed to establish whether hippocampal volume was reduced in patients with untreated adult-onset hypothyroidism compared to age-matched healthy controls. High-resolution magnetization-prepared rapid acquisition with gradient echo (MPRAGE) scans were performed on 11 untreated hypothyroid adults and 9 age-matched control subjects. Hypothyroidism was diagnosed based on increased levels of thyrotropin (TSH) and reduced levels of free thyroxine (fT4). Volumetric analysis of the right and left hippocampal regions, using functional magnetic resonance imaging of the brain (FMRIB) integrated registration and segmentation tool (FIRST), demonstrated significant volume reduction in the right hippocampus in the hypothyroid patients relative to the control group. These findings provide preliminary evidence that hypothyroidism results in structural deficits in the adult human brain. Decreases in volume in the right hippocampus were evident in patients with adult-onset overt hypothyroidism, supporting some of the findings in animal models.

Pegylated Long-Acting Human Growth Hormone Possesses a Promising Once-Weekly Treatment Profile, and Multiple Dosing Is Well Tolerated in Adult Patients with Growth Hormone Deficiency

DEFF Research Database (Denmark)

Søndergaard, Esben; Klose, Marianne; Hansen, Mette

2011-01-01

Background: Recombinant human GH (rhGH) replacement therapy in children and adults currently requires daily sc injections for several years or lifelong, which may be both inconvenient and distressing for patients. NNC126-0083 is a pegylated rhGH developed for once-weekly administration. Objectives...

Pre-stimulus thalamic theta power predicts human memory formation.

Science.gov (United States)

Sweeney-Reed, Catherine M; Zaehle, Tino; Voges, Jürgen; Schmitt, Friedhelm C; Buentjen, Lars; Kopitzki, Klaus; Richardson-Klavehn, Alan; Hinrichs, Hermann; Heinze, Hans-Jochen; Knight, Robert T; Rugg, Michael D

2016-09-01

Pre-stimulus theta (4-8Hz) power in the hippocampus and neocortex predicts whether a memory for a subsequent event will be formed. Anatomical studies reveal thalamus-hippocampal connectivity, and lesion, neuroimaging, and electrophysiological studies show that memory processing involves the dorsomedial (DMTN) and anterior thalamic nuclei (ATN). The small size and deep location of these nuclei have limited real-time study of their activity, however, and it is unknown whether pre-stimulus theta power predictive of successful memory formation is also found in these subcortical structures. We recorded human electrophysiological data from the DMTN and ATN of 7 patients receiving deep brain stimulation for refractory epilepsy. We found that greater pre-stimulus theta power in the right DMTN was associated with successful memory encoding, predicting both behavioral outcome and post-stimulus correlates of successful memory formation. In particular, significant correlations were observed between right DMTN theta power and both frontal theta and right ATN gamma (32-50Hz) phase alignment, and frontal-ATN theta-gamma cross-frequency coupling. We draw the following primary conclusions. Our results provide direct electrophysiological evidence in humans of a role for the DMTN as well as the ATN in memory formation. Furthermore, prediction of subsequent memory performance by pre-stimulus thalamic oscillations provides evidence that post-stimulus differences in thalamic activity that index successful and unsuccessful encoding reflect brain processes specifically underpinning memory formation. Finally, the findings broaden the understanding of brain states that facilitate memory encoding to include subcortical as well as cortical structures. Copyright © 2016 Elsevier Inc. All rights reserved.

3D Culture for Self-Formation of the Cerebellum from Human Pluripotent Stem Cells Through Induction of the Isthmic Organizer.

Science.gov (United States)

Muguruma, Keiko

2017-01-01

Pluripotent stem cells (PSCs) possess self-organizing abilities in 3D culture. This property has been demonstrated in recent studies, including the generation of various neuroectodermal and endodermal tissues. For example, PSCs are able to differentiate into specific type of neural tissues, such as the neocortex and the optic cup, in response to local positional information brought about by signals during embryogenesis. In contrast, the generation of cerebellar tissue from PSCs requires a secondary induction by a signaling center, called the isthmic organizer, which first appears in the cell aggregate in 3D culture. Such developmental complexity of cerebellum has hampered establishment of effective differentiation culture system from PSCs, thus far.We recently reported that cerebellar neurons are generated from human PSCs (hPSCs). In this chapter, we describe an efficient protocol for differentiation of 3D cerebellar neuroepithelium from hPSCs. We also describe the protocols for further differentiation into specific neurons in the cerebellar cortex, such as Purkinje cells and the granule cells.

Human immunodeficiency virus testing behaviors among US adults: the roles of individual factors, legislative status, and public health resources.

Science.gov (United States)

Du, Ping; Camacho, Fabian; Zurlo, John; Lengerich, Eugene J

2011-09-01

The Centers for Disease Control and Prevention recommended an "opt-out" human immunodeficiency virus (HIV) testing strategy in 2006 for all persons aged 13 to 64 years at healthcare settings. We conducted this study to identify individual, health, and policy factors that may be associated with HIV testing in US adults. The 2008 Behavioral Risk Factors Surveillance System data were utilized. Individuals' residency states were classified into 4 categories based on the legislation status to HIV testing laws in 2007 and HIV/acquired immune deficiency syndrome morbidity. A multivariate logistic regression adjusting for survey designs was performed to examine factors associated with HIV testing. A total of 281,826 adults aged 18 to 64 years answered HIV testing questions in 2008. The proportions of US adults who had ever been tested for HIV increased from 35.9% in 2006 to 39.9% in 2008. HIV testing varied across the individual's characteristics including sociodemographics, access to regular health care, and risk for HIV infection. Compared with residents of "high morbidity-opt out" states, those living in "high morbidity-opt in" states with legislative restrictions for HIV testing had a slightly lower odds of being tested for HIV (adjusted odds ratio = 0.96; 95% confidence interval = 0.92, 1.01). Adults living in "low morbidity" states were significantly less likely to be tested for HIV, regardless of legislative status. To implement routine HIV testing in the general population, the role of public health resources should be emphasized and legislative barriers should be further reduced. Strategies need to be developed to reach people who do not have regular access to health care.

Conical expansion of the outer subventricular zone and the role of neocortical folding in evolution and development

Directory of Open Access Journals (Sweden)

Eric eLewitus

2013-08-01

Full Text Available There is a basic rule to mammalian neocortical expansion: as it expands, so does it fold. The degree to which it folds, however, cannot strictly be attributed to its expansion. Across species, cortical volume does not keep pace with cortical surface area, but rather folds appear more rapidly than expected. As a result, larger brains quickly become disproportionately more convoluted than smaller brains. Both the absence (lissencephaly and presence (gyrencephaly of cortical folds is observed in all mammalian orders and, while there is likely some phylogenetic signature to the evolutionary appearance of gyri and sulci, there are undoubtedly universal trends to the acquisition of folds in an expanding neocortex. Whether these trends are governed by conical expansion of neocortical germinal zones, the distribution of cortical connectivity, or a combination of growth- and connectivity-driven forces remains an open question. But the importance of cortical folding for evolution of the uniquely mammalian neocortex, as well as for the incidence of neuropathologies in humans, is undisputed. In this hypothesis and theory article, we will summarize the development of cortical folds in the neocortex, consider the relative influence of growth- versus connectivity-driven forces for the acquisition of cortical folds between and within species, assess the genetic, cell-biological, and mechanistic implications for neocortical expansion, and discuss the significance of these implications for human evolution, development, and disease. We will argue that evolutionary increases in the density of neuron production, achieved via maintenance of a basal proliferative niche in the neocortical germinal zones, drive the conical migration of neurons towards the cortical surface and ultimately lead to the establishment of cortical folds in large-brained mammal species.

BAY11 enhances OCT4 synthetic mRNA expression in adult human skin cells.

Science.gov (United States)

Awe, Jason P; Crespo, Agustin Vega; Li, You; Kiledjian, Megerditch; Byrne, James A

2013-02-06

The OCT4 transcription factor is involved in many cellular processes, including development, reprogramming, maintaining pluripotency and differentiation. Synthetic OCT4 mRNA was recently used (in conjunction with other reprogramming factors) to generate human induced pluripotent stem cells. Here, we discovered that BAY 11-7082 (BAY11), at least partially through an NF-κB-inhibition based mechanism, could significantly increase the expression of OCT4 following transfection of synthetic mRNA (synRNA) into adult human skin cells. We tested various chemical and molecular small molecules on their ability to suppress the innate immune response seen upon synthetic mRNA transfection. Three molecules - B18R, BX795, and BAY11 - were used in immunocytochemical and proliferation-based assays. We also utilized global transcriptional meta-analysis coupled with quantitative PCR to identify relative gene expression downstream of OCT4. We found that human skin cells cultured in the presence of BAY11 resulted in reproducible increased expression of OCT4 that did not inhibit normal cell proliferation. The increased levels of OCT4 resulted in significantly increased expression of genes downstream of OCT4, including the previously identified SPP1, DUSP4 and GADD45G, suggesting the expressed OCT4 was functional. We also discovered a novel OCT4 putative downstream target gene SLC16A9 which demonstrated significantly increased expression following elevation of OCT4 levels. For the first time we have shown that small molecule-based stabilization of synthetic mRNA expression can be achieved with use of BAY11. This small molecule-based inhibition of innate immune responses and subsequent robust expression of transfected synthetic mRNAs may have multiple applications for future cell-based research and therapeutics.

The Persuasive Program in Adult Education: Theory and Planning.

Science.gov (United States)

Atkinson, Thomas Grant

The purpose of this study was to investigate, develop, and explicate a procedure, theoretical in nature, which adult educators can use for comprehending, analyzing and planning single-event persuasive programs for adults. The study conceptualized persuasion as a behavioral phenomenon consisting of verifiable human action which constitutes, or is…

In vivo transplantation of neurosphere-like bodies derived from the human postnatal and adult enteric nervous system: a pilot study.

Directory of Open Access Journals (Sweden)

Susan Hetz

Full Text Available Recent advances in the in vitro characterization of human adult enteric neural progenitor cells have opened new possibilities for cell-based therapies in gastrointestinal motility disorders. However, whether these cells are able to integrate within an in vivo gut environment is still unclear. In this study, we transplanted neural progenitor-containing neurosphere-like bodies (NLBs in a mouse model of hypoganglionosis and analyzed cellular integration of NLB-derived cell types and functional improvement. NLBs were propagated from postnatal and adult human gut tissues. Cells were characterized by immunohistochemistry, quantitative PCR and subtelomere fluorescence in situ hybridization (FISH. For in vivo evaluation, the plexus of murine colon was damaged by the application of cationic surfactant benzalkonium chloride which was followed by the transplantation of NLBs in a fibrin matrix. After 4 weeks, grafted human cells were visualized by combined in situ hybridization (Alu and immunohistochemistry (PGP9.5, GFAP, SMA. In addition, we determined nitric oxide synthase (NOS-positive neurons and measured hypertrophic effects in the ENS and musculature. Contractility of treated guts was assessed in organ bath after electrical field stimulation. NLBs could be reproducibly generated without any signs of chromosomal alterations using subtelomere FISH. NLB-derived cells integrated within the host tissue and showed expected differentiated phenotypes i.e. enteric neurons, glia and smooth muscle-like cells following in vivo transplantation. Our data suggest biological effects of the transplanted NLB cells on tissue contractility, although robust statistical results could not be obtained due to the small sample size. Further, it is unclear, which of the NLB cell types including neural progenitors have direct restoring effects or, alternatively may act via 'bystander' mechanisms in vivo. Our findings provide further evidence that NLB transplantation can be

Regional aerosol deposition in human upper airways

Energy Technology Data Exchange (ETDEWEB)

Swift, D.L.

1992-11-01

Laboratory experimental studies were carried out to investigate the factors influencing the deposition of aerosols ranging in size from 1 nm to 10 [mu]m in the human nasal, oral, pharyngeal and laryngeal airways. These experimental studies were performed in replicate upper airway physical models and in human volunteer subjects. New replicate models of the oral passage of an infant, the oral passage of an adult at two openings and the combined nasal and oral airways of an adult were constructed during the period, adding to the existing models of adult, child and infant nasal and oral airways models. Deposition studies in the adult oral and adult nasal models were performed under simulated cyclic flow conditions with 1 nm particles to compare with previously measured constant flow studies. Similar studies with inertial particles (1--10 [mu]m diameter) were performed with the adult nasal model; in both instances, results with cyclic flow were similar to constant flow results using a simple average flow rate based on inspiratory volume and time of inspiration. Human subject studies were performed with particle sizes 5--20 nm for nasal inspiration; preliminary analysis shows good agreement with model studies at several representative flow rates. Nasal inspiratory inertial deposition of 1--4 [mu]m diameter particles was measured in several adults as a function of airway dimensions; dimensional changes of the valve area by decongestion did not produce concomitant deposition changes.

The Role of Ontogeny in the Evolution of Human Cooperation.

Science.gov (United States)

Tomasello, Michael; Gonzalez-Cabrera, Ivan

2017-09-01

To explain the evolutionary emergence of uniquely human skills and motivations for cooperation, Tomasello et al. (2012, in Current Anthropology 53(6):673-92) proposed the interdependence hypothesis. The key adaptive context in this account was the obligate collaborative foraging of early human adults. Hawkes (2014, in Human Nature 25(1):28-48), following Hrdy (Mothers and Others, Harvard University Press, 2009), provided an alternative account for the emergence of uniquely human cooperative skills in which the key was early human infants' attempts to solicit care and attention from adults in a cooperative breeding context. Here we attempt to reconcile these two accounts. Our composite account accepts Hrdy's and Hawkes's contention that the extremely early emergence of human infants' cooperative skills suggests an important role for cooperative breeding as adaptive context, perhaps in early Homo. But our account also insists that human cooperation goes well beyond these nascent skills to include such things as the communicative and cultural conventions, norms, and institutions created by later Homo and early modern humans to deal with adult problems of social coordination. As part of this account we hypothesize how each of the main stages of human ontogeny (infancy, childhood, adolescence) was transformed during evolution both by infants' cooperative skills "migrating up" in age and by adults' cooperative skills "migrating down" in age.

Development of a physiologically based pharmacokinetic model for assessment of human exposure to bisphenol A

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Yang, Xiaoxia, E-mail: xiaoxia.yang@fda.hhs.gov [Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Doerge, Daniel R. [Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Teeguarden, Justin G. [Health Effects and Exposure Science, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Fisher, Jeffrey W. [Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States)

2015-12-15

A previously developed physiologically based pharmacokinetic (PBPK) model for bisphenol A (BPA) in adult rhesus monkeys was modified to characterize the pharmacokinetics of BPA and its phase II conjugates in adult humans following oral ingestion. Coupled with in vitro studies on BPA metabolism in the liver and the small intestine, the PBPK model was parameterized using oral pharmacokinetic data with deuterated-BPA (d{sub 6}-BPA) delivered in cookies to adult humans after overnight fasting. The availability of the serum concentration time course of unconjugated d{sub 6}-BPA offered direct empirical evidence for the calibration of BPA model parameters. The recalibrated PBPK adult human model for BPA was then evaluated against published human pharmacokinetic studies with BPA. A hypothesis of decreased oral uptake was needed to account for the reduced peak levels observed in adult humans, where d{sub 6}-BPA was delivered in soup and food was provided prior to BPA ingestion, suggesting the potential impact of dosing vehicles and/or fasting on BPA disposition. With the incorporation of Monte Carlo analysis, the recalibrated adult human model was used to address the inter-individual variability in the internal dose metrics of BPA for the U.S. general population. Model-predicted peak BPA serum levels were in the range of pM, with 95% of human variability falling within an order of magnitude. This recalibrated PBPK model for BPA in adult humans provides a scientific basis for assessing human exposure to BPA that can serve to minimize uncertainties incurred during extrapolations across doses and species. - Highlights: • A PBPK model predicts the kinetics of bisphenol A (BPA) in adult humans. • Serum concentrations of aglycone BPA are available for model calibration. • Model predicted peak BPA serum levels for adult humans were in the range of pM. • Model predicted 95% of human variability fell within an order of magnitude.

Human Salivary Gland Stem Cells Functionally Restore Radiation Damaged Salivary Glands

DEFF Research Database (Denmark)

Pringle, Sarah; Maimets, Martti; van der Zwaag, Marianne

2016-01-01

Adult stem cells are often touted as therapeutic agents in the regenerative medicine field, however data detailing both the engraftment and functional capabilities of solid tissue derived human adult epithelial stem cells is scarce. Here we show the isolation of adult human salivary gland (SG) st...... for the first time that salispheres cultured from human SGs contain stem/progenitor cells capable of self-renewal and differentiation and rescue of saliva production. Our study underpins the therapeutic promise of salisphere cell therapy for the treatment of xerostomia....

Effects of arousal and context on recognition memory for emotional pictures in younger and older adults

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Wang, Yang; Yang, Jiongjiong

2017-01-01

Background/Study context Previous studies found that older adults tend to remember more positive than negative information (i.e., positivity bias), leading to an age-related positivity effect. However, the extent to which factors of arousal and contextual information influence the positivity bias in older adults remains to be determined. Methods In this study, 27 Chinese younger adults (20.00±1.75 years) and 33 Chinese older adults (70.76 ± 5.49) learned pictures with negative, positive and neutral valences. Half of the pictures had a human context, and the other half did not. In addition, emotional dimensions of negative and positive pictures were divided into high-arousal and low-arousal. The experimental task was to provide old/new recognition and confidence rating judgments. Results Both groups of subjects showed the positivity bias for low-arousal pictures, but the positivity bias was restricted to low-arousal pictures without the human context in older adults. In addition, the positivity bias was mainly driven by the recollection process in younger adults, and it was mainly driven by both the recollection and familiarity processes in older adults. The recognition of the nonhuman positive pictures was correlated with cognitive control abilities, but the recognition of pictures with human contexts was correlated with general memory abilities in older adults. Conclusion This study highlights the importance of arousal and contextual information in modulating emotional memory in younger and older adults. It suggests that there are different mechanisms for memorizing pictures with and without human contexts in older adults. PMID:28230422

Surface Hydrophilicity of Poly(l-Lactide Acid Polymer Film Changes the Human Adult Adipose Stem Cell Architecture

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Chiara Argentati

2018-02-01

Full Text Available Current knowledge indicates that the molecular cross-talk between stem cells and biomaterials guides the stem cells’ fate within a tissue engineering system. In this work, we have explored the effects of the interaction between the poly(l-lactide acid (PLLA polymer film and human adult adipose stem cells (hASCs, focusing on the events correlating the materials’ surface characteristics and the cells’ plasma membrane. hASCs were seeded on films of pristine PLLA polymer and on a PLLA surface modified by the radiofrequency plasma method under oxygen flow (PLLA+O2. Comparative experiments were performed using human bone-marrow mesenchymal stem cells (hBM-MSCs and human umbilical matrix stem cells (hUCMSCs. After treatment with oxygen-plasma, the surface of PLLA films became hydrophilic, whereas the bulk properties were not affected. hASCs cultured on pristine PLLA polymer films acquired a spheroid conformation. On the contrary, hASCs seeded on PLLA+O2 film surface maintained the fibroblast-like morphology typically observed on tissue culture polystyrene. This suggests that the surface hydrophilicity is involved in the acquisition of the spheroid conformation. Noteworthy, the oxygen treatment had no effects on hBM-MSC and hUCMSC cultures and both stem cells maintained the same shape observed on PLLA films. This different behavior suggests that the biomaterial-interaction is stem cell specific.

Quantification of 5-HT{sub 1A} receptors in human brain using p-MPPF kinetic modelling and PET

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Sanabria-Bohorquez, S.M.; Veraart, C. [Neural Rehabilitation Engineering Lab., Univ. Catholique de Louvain, Brussels (Belgium); Biver, F.; Damhaut, P.; Wikler, D.; Goldman, S. [PET/Biomedical Cyclotron Unit, Univ. Libre de Bruxelles (Belgium)

2002-01-01

Serotonin-1A (5-HT{sub 1A}) receptors are implicated in neurochemical mechanisms underlying anxiety and depression and their treatment. Animal studies have suggested that 4-(2'-methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)-p-[{sup 18}F]fluorobenzamido] ethyl] piperazine (p-MPPF) may be a suitable positron emission tomography (PET) tracer of 5-HT{sub 1A} receptors. To test p-MPPF in humans, we performed 60-min dynamic PET scans in 13 healthy volunteers after single bolus injection. Metabolite quantification revealed a fast decrease in tracer plasma concentration, such that at 5 min post injection about 25% of the total radioactivity in plasma corresponded to p-MPPF. Radioactivity concentration was highest in hippocampus, intermediate in neocortex and lowest in basal ganglia and cerebellum. The interactions between p-MPPF and 5-HT{sub 1A} receptors were described using linear compartmental models with plasma input and reference tissue approaches. The two quantification methods provided similar results which are in agreement with previous reports on 5-HT{sub 1A} receptor brain distribution. In conclusion, our results show that p-MPPF is a suitable PET radioligand for 5-HT{sub 1A} receptor human studies. (orig.)

Higher prevalence of human papillomavirus infection in adolescent and young adult girls belonging to different Indian tribes with varied socio-sexual lifestyle.

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Kirti Sharma

Full Text Available Despite high prevalence of human papillomavirus (HPV infection and cervical cancer in Indian women, no study has been done in tribal populations whose socio-sexual lifestyle is different. Therefore, HPV screening has been carried out in pre-adolescent, adolescent and young adult tribal girls using self-collected urine samples.20-35 ml self-collected midstream urine samples were obtained from a total of 2278 healthy tribal girls (9-25 years comprising pre-adolescent, adolescent and young adults from three Indian states: Madhya Pradesh, Jharkhand and Chhattisgarh. β-globin positive 2034 samples were employed for HPV detection and genotyping.The overall prevalence of HPV infection in tribal girls was 12.9% (262/2034. More than 65% (172/262 of them were infected with HR-HPV types of which HPV16 was the most predominant type (54%. Young adult girls aged 18-25 years showed a significantly higher prevalence of HPV infection (19.2%; OR = 3.36; 95% CI 2.97-6.34, P<0.001 as compared to that in adolescent (11.4%; OR = 1.82; 95% CI 1.20-2.76, P<0.01 or pre-adolescent girls (6.6%.This is a first study showing significantly a very high prevalence of HPV infection in adolescent and young adult tribal girls possibly due to different socio-sexual behavior, indicating a serious health concern for Indian tribal women.

Delivery of Human EV71 Receptors by Adeno-Associated Virus Increases EV71 Infection-Induced Local Inflammation in Adult Mice

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Hung-Bo Hsiao

2014-01-01

Full Text Available Enterovirus71 (EV71 is now recognized as an emerging neurotropic virus in Asia and one major causative agent of hand-foot-mouth diseases (HFMD. However potential animal models for vaccine development are limited to young mice. In this study, we used an adeno-associated virus (AAV vector to introduce the human EV71 receptors P-selectin glycoprotein ligand-1 (hPSGL1 or a scavenger receptor class-B member-2 (hSCARB2 into adult ICR mice to change their susceptibility to EV71 infection. Mice were administered AAV-hSCARB2 or AAV-hPSGL1 through intravenous and oral routes. After three weeks, expression of human SCARB2 and PSGL1 was detected in various organs. After infection with EV71, we found that the EV71 viral load in AAV-hSCARB2- or AAV-hPSGL1-transduced mice was higher than that of the control mice in both the brain and intestines. The presence of EV71 viral particles in tissues was confirmed using immunohistochemistry analysis. Moreover, inflammatory cytokines were induced in the brain and intestines of AAV-hSCARB2- or AAV-hPSGL1-transduced mice after EV71 infection but not in wild-type mice. However, neurological disease was not observed in these animals. Taken together, we successfully infected adult mice with live EV71 and induced local inflammation using an AAV delivery system.

Delayed intramuscular human neurotrophin-3 improves recovery in adult and elderly rats after stroke.

Science.gov (United States)

Duricki, Denise A; Hutson, Thomas H; Kathe, Claudia; Soleman, Sara; Gonzalez-Carter, Daniel; Petruska, Jeffrey C; Shine, H David; Chen, Qin; Wood, Tobias C; Bernanos, Michel; Cash, Diana; Williams, Steven C R; Gage, Fred H; Moon, Lawrence D F

2016-01-01

There is an urgent need for a therapy that reverses disability after stroke when initiated in a time frame suitable for the majority of new victims. We show here that intramuscular delivery of neurotrophin-3 (NT3, encoded by NTF3) can induce sensorimotor recovery when treatment is initiated 24 h after stroke. Specifically, in two randomized, blinded preclinical trials, we show improved sensory and locomotor function in adult (6 months) and elderly (18 months) rats treated 24 h following cortical ischaemic stroke with human NT3 delivered using a clinically approved serotype of adeno-associated viral vector (AAV1). Importantly, AAV1-hNT3 was given in a clinically-feasible timeframe using a straightforward, targeted route (injections into disabled forelimb muscles). Magnetic resonance imaging and histology showed that recovery was not due to neuroprotection, as expected given the delayed treatment. Rather, treatment caused corticospinal axons from the less affected hemisphere to sprout in the spinal cord. This treatment is the first gene therapy that reverses disability after stroke when administered intramuscularly in an elderly body. Importantly, phase I and II clinical trials by others show that repeated, peripherally administered high doses of recombinant NT3 are safe and well tolerated in humans with other conditions. This paves the way for NT3 as a therapy for stroke. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The predictive nature of transcript expression levels on protein expression in adult human brain.

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Bauernfeind, Amy L; Babbitt, Courtney C

2017-04-24

Next generation sequencing methods are the gold standard for evaluating expression of the transcriptome. When determining the biological implications of such studies, the assumption is often made that transcript expression levels correspond to protein levels in a meaningful way. However, the strength of the overall correlation between transcript and protein expression is inconsistent, particularly in brain samples. Following high-throughput transcriptomic (RNA-Seq) and proteomic (liquid chromatography coupled with tandem mass spectrometry) analyses of adult human brain samples, we compared the correlation in the expression of transcripts and proteins that support various biological processes, molecular functions, and that are located in different areas of the cell. Although most categories of transcripts have extremely weak predictive value for the expression of their associated proteins (R 2 values of < 10%), transcripts coding for protein kinases and membrane-associated proteins, including those that are part of receptors or ion transporters, are among those that are most predictive of downstream protein expression levels. The predictive value of transcript expression for corresponding proteins is variable in human brain samples, reflecting the complex regulation of protein expression. However, we found that transcriptomic analyses are appropriate for assessing the expression levels of certain classes of proteins, including those that modify proteins, such as kinases and phosphatases, regulate metabolic and synaptic activity, or are associated with a cellular membrane. These findings can be used to guide the interpretation of gene expression results from primate brain samples.

Epidemic myalgia and myositis associated with human parechovirus type 3 infections occur not only in adults but also in children: findings in Yamagata, Japan, 2014.

Science.gov (United States)

Mizuta, K; Yamakawa, T; Kurokawa, K; Chikaoka, S; Shimizu, Y; Itagaki, T; Katsushima, F; Katsushima, Y; Ito, S; Aoki, Y; Matoba, Y; Tanaka, S; Yahagi, K

2016-04-01

We previously reported an association between human parechovirus type 3 (HPeV3) and epidemic myalgia with myositis in adults during summers in which an HPeV3 outbreak occurred in children. However, this disease association has not yet been reported elsewhere. We have since continued our surveillance to accumulate data on this disease association and to confirm whether myalgia occurs in children as well as adults. Between June and August 2014, we collected 380 specimens from children with infectious diseases. We also collected clinical specimens from two adult and three paediatric patients suspected of myalgia. We then performed virus isolation and reverse-transcription-PCR using the collected specimens. We detected HPeV3 in 26 children with infectious diseases, which we regarded as indicating an outbreak. We also confirmed HPeV3 infection in all patients suspected of myalgia. In particular the symptoms in two boys, complaining of myalgia and fever, closely matched the criteria for adult myalgia. Based on our findings from 2008, 2011 and 2014, we again urge that clinical consideration be given to the relationship between myalgia and HPeV3 infections during HPeV3 outbreaks in children. Furthermore, our observations from 2014 suggest that epidemic myalgia and myositis occur not only in adults but also in children.

Empathy in Adult Education

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Natalija Vrečer

2015-10-01

Full Text Available Empathy is an important part of emotional intelligence and the latter is crucial for human relations, whether they be interpersonal relations, relations among people at work, or in a wider community. Therefore, empathy is important for adult education, for guidance counsellors, and for other adult educators. Adult educators must be empathic in order to understand the perspectives and needs of the participants in the educational process and empathy is a precondition for understanding. The development of empathy as a competence is a lifelong learning process. Namely, despite some biological predispositions for empathy, the latter can be learnt. It is the contention of the article that empathy is one of the most important intercultural competencies, because if a person is not empathic, other intercultural competencies vary rarely cannot develop to their full extent. Thus empathy is a precondition for successful intercultural dialogue.

Human Capital Development: Reforms for Adult and Community Education

Science.gov (United States)

Choy, Sarojni; Haukka, Sandra

2007-01-01

The adult and community education (ACE) sector is consistently responsive to changing community needs and government priorities. It is this particular function that has drawn ACE into the lifelong learning debate as one model for sustaining communities. The responsiveness of ACE means that the sector and its programs continue to make valuable…

Sphingosine-1-phosphate mediates proliferation maintaining the multipotency of human adult bone marrow and adipose tissue-derived stem cells.

Science.gov (United States)

He, Xiaoli; H'ng, Shiau-Chen; Leong, David T; Hutmacher, Dietmar W; Melendez, Alirio J

2010-08-01

High renewal and maintenance of multipotency of human adult stem cells (hSCs), are a prerequisite for experimental analysis as well as for potential clinical usages. The most widely used strategy for hSC culture and proliferation is using serum. However, serum is poorly defined and has a considerable degree of inter-batch variation, which makes it difficult for large-scale mesenchymal stem cells (MSCs) expansion in homogeneous culture conditions. Moreover, it is often observed that cells grown in serum-containing media spontaneously differentiate into unknown and/or undesired phenotypes. Another way of maintaining hSC development is using cytokines and/or tissue-specific growth factors; this is a very expensive approach and can lead to early unwanted differentiation. In order to circumvent these issues, we investigated the role of sphingosine-1-phosphate (S1P), in the growth and multipotency maintenance of human bone marrow and adipose tissue-derived MSCs. We show that S1P induces growth, and in combination with reduced serum, or with the growth factors FGF and platelet-derived growth factor-AB, S1P has an enhancing effect on growth. We also show that the MSCs cultured in S1P-supplemented media are able to maintain their differentiation potential for at least as long as that for cells grown in the usual serum-containing media. This is shown by the ability of cells grown in S1P-containing media to be able to undergo osteogenic as well as adipogenic differentiation. This is of interest, since S1P is a relatively inexpensive natural product, which can be obtained in homogeneous high-purity batches: this will minimize costs and potentially reduce the unwanted side effects observed with serum. Taken together, S1P is able to induce proliferation while maintaining the multipotency of different human stem cells, suggesting a potential for S1P in developing serum-free or serum-reduced defined medium for adult stem cell cultures.

Pegylated Long-Acting Human Growth Hormone Possesses a Promising Once-Weekly Treatment Profile, and Multiple Dosing Is Well Tolerated in Adult Patients with Growth Hormone Deficiency

DEFF Research Database (Denmark)

Søndergaard, Esben; Klose, Marianne Christina; Hansen, Mette

2011-01-01

Background: Recombinant human GH (rhGH) replacement therapy in children and adults currently requires daily sc injections for several years or lifelong, which may be both inconvenient and distressing for patients. NNC126-0083 is a pegylated rhGH developed for once-weekly administration. Objectives......: Our objective was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of NNC126-0083 in adult patients with GH deficiency (GHD). Subjects and Methods: Thirty-three adult patients with GHD, age 20-65 yr, body mass index 18.5-35.0 kg/m(2), and glycated...... to 240 h after the third dosing. Physical examination, antibodies, and local tolerability were assessed. Results: NNC126-0083 was well tolerated with no difference in local tolerability compared with placebo and with no signs of lipoatrophy. A more than dose-proportional exposure was observed...

The evidence for increased L1 activity in the site of human adult brain neurogenesis.

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Alexey A Kurnosov

Full Text Available Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus-the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory.

Second generation codon optimized minicircle (CoMiC) for nonviral reprogramming of human adult fibroblasts.

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Diecke, Sebastian; Lisowski, Leszek; Kooreman, Nigel G; Wu, Joseph C

2014-01-01

The ability to induce pluripotency in somatic cells is one of the most important scientific achievements in the fields of stem cell research and regenerative medicine. This technique allows researchers to obtain pluripotent stem cells without the controversial use of embryos, providing a novel and powerful tool for disease modeling and drug screening approaches. However, using viruses for the delivery of reprogramming genes and transcription factors may result in integration into the host genome and cause random mutations within the target cell, thus limiting the use of these cells for downstream applications. To overcome this limitation, various non-integrating techniques, including Sendai virus, mRNA, minicircle, and plasmid-based methods, have recently been developed. Utilizing a newly developed codon optimized 4-in-1 minicircle (CoMiC), we were able to reprogram human adult fibroblasts using chemically defined media and without the need for feeder cells.

Human infant faces provoke implicit positive affective responses in parents and non-parents alike.

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Senese, Vincenzo Paolo; De Falco, Simona; Bornstein, Marc H; Caria, Andrea; Buffolino, Simona; Venuti, Paola

2013-01-01

Human infants' complete dependence on adult caregiving suggests that mechanisms associated with adult responsiveness to infant cues might be deeply embedded in the brain. Behavioural and neuroimaging research has produced converging evidence for adults' positive disposition to infant cues, but these studies have not investigated directly the valence of adults' reactions, how they are moderated by biological and social factors, and if they relate to child caregiving. This study examines implicit affective responses of 90 adults toward faces of human and non-human (cats and dogs) infants and adults. Implicit reactions were assessed with Single Category Implicit Association Tests, and reports of childrearing behaviours were assessed by the Parental Style Questionnaire. The results showed that human infant faces represent highly biologically relevant stimuli that capture attention and are implicitly associated with positive emotions. This reaction holds independent of gender and parenthood status and is associated with ideal parenting behaviors.

Cortical cholinergic deficiency enhances amphetamine-induced dopamine release in the accumbens but not striatum.

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Mattsson, Anna; Olson, Lars; Svensson, Torgny H; Schilström, Björn

2007-11-01

Cholinergic dysfunction has been implicated as a putative contributing factor in the pathogenesis of schizophrenia. Recently, we showed that cholinergic denervation of the neocortex in adult rats leads to a marked increase in the behavioral response to amphetamine. The main objective of this study was to investigate if the enhanced locomotor response to amphetamine seen after cortical cholinergic denervation was paralleled by an increased amphetamine-induced release of dopamine in the nucleus accumbens and/or striatum. The corticopetal cholinergic projections were lesioned by intraparenchymal infusion of 192 IgG-saporin into the nucleus basalis magnocellularis of adult rats. Amphetamine-induced dopamine release in the nucleus accumbens or striatum was monitored by in vivo microdialysis 2 to 3 weeks after lesioning. We found that cholinergic denervation of the rat neocortex leads to a significantly increased amphetamine-induced dopamine release in the nucleus accumbens. Interestingly, the cholinergic lesion did not affect amphetamine-induced release of dopamine in the striatum. The enhanced amphetamine-induced dopamine release in the nucleus accumbens in the cholinergically denervated rats could be reversed by administration of the muscarinic agonist oxotremorine, but not nicotine, prior to the amphetamine challenge, suggesting that loss of muscarinic receptor stimulation is likely to have caused the observed effect. The results suggest that abnormal responsiveness of dopamine neurons can be secondary to cortical cholinergic deficiency. This, in turn, might be of relevance for the pathophysiology of schizophrenia and provides a possible link between cholinergic disturbances and alteration of dopamine transmission.

Medicaid CMS-64 New Adult Group Expenditures

Data.gov (United States)

U.S. Department of Health & Human Services — This dataset reports summary level expenditure data associated with the new adult group established under the Affordable Care Act. These state expenditures are...

Enhanced striatal sensitivity to aversive reinforcement in adolescents versus adults.

Science.gov (United States)

Galván, Adriana; McGlennen, Kristine M

2013-02-01

Neurodevelopmental changes in mesolimbic regions are associated with adolescent risk-taking behavior. Numerous studies have shown exaggerated activation in the striatum in adolescents compared with children and adults during reward processing. However, striatal sensitivity to aversion remains elusive. Given the important role of the striatum in tracking both appetitive and aversive events, addressing this question is critical to understanding adolescent decision-making, as both positive and negative factors contribute to this behavior. In this study, human adult and adolescent participants performed a task in which they received squirts of appetitive or aversive liquid while undergoing fMRI, a novel approach in human adolescents. Compared with adults, adolescents showed greater behavioral and striatal sensitivity to both appetitive and aversive stimuli, an effect that was exaggerated in response to delivery of the aversive stimulus. Collectively, these findings contribute to understanding how neural responses to positive and negative outcomes differ between adolescents and adults and how they may influence adolescent behavior.

Polysialylated-neural cell adhesion molecule (PSA-NCAM in the human trigeminal ganglion and brainstem at prenatal and adult ages

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Melis Tiziana

2008-11-01

Full Text Available Abstract Background The polysialylated neuronal cell adhesion molecule (PSA-NCAM is considered a marker of developing and migrating neurons and of synaptogenesis in the immature vertebrate nervous system. However, it persists in the mature normal brain in some regions which retain a capability for morphofunctional reorganization throughout life. With the aim of providing information relevant to the potential for dynamic changes of specific neuronal populations in man, this study analyses the immunohistochemical occurrence of PSA-NCAM in the human trigeminal ganglion (TG and brainstem neuronal populations at prenatal and adult age. Results Western blot analysis in human and rat hippocampus supports the specificity of the anti-PSA-NCAM antibody and the immunodetectability of the molecule in postmortem tissue. Immunohistochemical staining for PSA-NCAM occurs in TG and several brainstem regions during prenatal life and in adulthood. As a general rule, it appears as a surface staining suggestive of membrane labelling on neuronal perikarya and proximal processes, and as filamentous and dot-like elements in the neuropil. In the TG, PSA-NCAM is localized to neuronal perikarya, nerve fibres, pericellular networks, and satellite and Schwann cells; further, cytoplasmic perikaryal staining and positive pericellular fibre networks are detectable with higher frequency in adult than in newborn tissue. In the adult tissue, positive neurons are mostly small- and medium-sized, and amount to about 6% of the total ganglionic population. In the brainstem, PSA-NCAM is mainly distributed at the level of the medulla oblongata and pons and appears scarce in the mesencephalon. Immunoreactivity also occurs in discretely localized glial structures. At all ages examined, PSA-NCAM occurs in the spinal trigeminal nucleus, solitary nuclear complex, vestibular and cochlear nuclei, reticular formation nuclei, and most of the precerebellar nuclei. In specimens of different age

Alternative Sources of Adult Stem Cells: Human Amniotic Membrane

Science.gov (United States)

Wolbank, Susanne; van Griensven, Martijn; Grillari-Voglauer, Regina; Peterbauer-Scherb, Anja

Human amniotic membrane is a highly promising cell source for tissue engineering. The cells thereof, human amniotic epithelial cells (hAEC) and human amniotic mesenchymal stromal cells (hAMSC), may be immunoprivileged, they represent an early developmental status, and their application is ethically uncontroversial. Cell banking strategies may use freshly isolated cells or involve in vitro expansion to increase cell numbers. Therefore, we have thoroughly characterized the effect of in vitro cultivation on both phenotype and differentiation potential of hAEC. Moreover, we present different strategies to improve expansion including replacement of animal-derived supplements by human platelet products or the introduction of the catalytic subunit of human telomerase to extend the in vitro lifespan of amniotic cells. Characterization of the resulting cultures includes phenotype, growth characteristics, and differentiation potential, as well as immunogenic and immunomodulatory properties.

Adult and Non-Formal Education: An Imperative for Human Capacity ...

African Journals Online (AJOL)

DR Nneka

capacity development could be defined as the development of a workforce .... and the community and between theory and practice in Adult Education, ... ANFE provides education for women in order to empower them, enable them gain.

Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans.

Science.gov (United States)

Carroll, Judith E; Cole, Steven W; Seeman, Teresa E; Breen, Elizabeth C; Witarama, Tuff; Arevalo, Jesusa M G; Ma, Jeffrey; Irwin, Michael R

2016-01-01

Age-related disease risk has been linked to short sleep duration and sleep disturbances; however, the specific molecular pathways linking sleep loss with diseases of aging are poorly defined. Key cellular events seen with aging, which are thought to contribute to disease, may be particularly sensitive to sleep loss. We tested whether one night of partial sleep deprivation (PSD) would increase leukocyte gene expression indicative of DNA damage responses (DDR), the senescence-associated secretory phenotype (SASP), and senescence indicator p16(INK4a) in older adult humans, who are at increased risk for cellular senescence. Community-dwelling older adults aged 61-86years (n=29; 48% male) underwent an experimental partial sleep deprivation (PSD) protocol over 4 nights, including adaptation, an uninterrupted night of sleep, partial sleep deprivation (sleep restricted 3-7AM), and a subsequent full night of sleep. Blood samples were obtained each morning to assess peripheral blood mononuclear cell (PBMC) gene expression using Illumina HT-12 arrays. Analyses of microarray results revealed that SASP (psleep deprivation activates PBMC gene expression patterns consistent with biological aging in this older adult sample. PSD enhanced the SASP and increased the accumulation of damage that initiates cell cycle arrest and promotes cellular senescence. These findings causally link sleep deprivation to the molecular processes associated with biological aging. Copyright © 2015 Elsevier Inc. All rights reserved.

Plasma membrane proteomics of human embryonic stem cells and human embryonal carcinoma cells.

NARCIS (Netherlands)

Dormeyer, W.; van Hoof, D.; Braam, S.R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

2008-01-01

Human embryonic stem cells (hESCs) are of immense interest in regenerative medicine as they can self-renew indefinitely and can give rise to any adult cell type. Human embryonal carcinoma cells (hECCs) are the malignant counterparts of hESCs found in testis tumors. hESCs that have acquired

Epidemiology of Human Papillomavirus Detected in the Oral Cavity and Fingernails of Mid-Adult Women.

Science.gov (United States)

Fu, Tsung-chieh Jane; Hughes, James P; Feng, Qinghua; Hulbert, Ayaka; Hawes, Stephen E; Xi, Long Fu; Schwartz, Stephen M; Stern, Joshua E; Koutsky, Laura A; Winer, Rachel L

2015-12-01

Oral and fingernail human papillomavirus (HPV) detection may be associated with HPV-related carcinoma risk at these nongenital sites and foster transmission to the genitals. We describe the epidemiology of oral and fingernail HPV among mid-adult women. Between 2011 and 2012, 409 women aged 30 to 50 years were followed up for 6 months. Women completed health and behavior surveys and provided self-collected oral, fingernail, and vaginal specimens at enrollment and exit for type-specific HPV DNA testing. Concordance of type-specific HPV detection across anatomical sites was described with κ statistics. Using generalized estimating equations or exact logistic regression, we measured the univariate associations of various risk factors with type-specific oral and fingernail HPV detection. Prevalence of detecting HPV in the oral cavity (2.4%) and fingernails (3.8%) was low compared with the vagina (33.1%). Concordance across anatomical sites was poor (κ history (OR, 11.1; 95% CI, 2.8-infinity), lifetime number of male vaginal sex partners at least 10 (OR vs. 0-3 partners, 5.0; 95% CI, 1.2-infinity), and lifetime number of open-mouth kissing partners at least 16 (OR vs. 0-15 partners, infinity; 95% CI, 2.6-infinity, by exact logistic regression) were each associated with oral HPV detection. Although our findings support HPV DNA deposition or autoinoculation between anatomical sites in mid-adult women, the rarity of HPV in the oral cavity and fingernails suggests that oral/fingernail HPV does not account for a significant fraction of HPV in genital sites.

Human-wildlife conflict: proximate predictors of aggression between humans and rhesus macaques in India.

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Beisner, Brianne A; Heagerty, Allison; Seil, Shannon K; Balasubramaniam, Krishna N; Atwill, Edward R; Gupta, Brij K; Tyagi, Praveen C; Chauhan, Netrapal P S; Bonal, B S; Sinha, P R; McCowan, Brenda

2015-02-01

Macaques live in close contact with humans across South and Southeast Asia, and direct interaction is frequent. Aggressive contact is a concern in many locations, particularly among populations of rhesus and longtail macaques that co-inhabit urbanized cities and towns with humans. We investigated the proximate factors influencing the occurrence of macaque aggression toward humans as well as human aggression toward macaques to determine the extent to which human behavior elicits macaque aggression and vice versa. We conducted a 3-month study of four free-ranging populations of rhesus macaques in Dehradun, India from October-December 2012, using event sampling to record all instances of human-macaque interaction (N = 3120). Our results show that while human aggression was predicted by the potential for economic losses or damage, macaque aggression was influenced by aggressive or intimidating behavior by humans as well as recent rates of conspecific aggression. Further, adult female macaques participated in aggression more frequently than expected, whereas adult and subadult males participated as frequently as expected. Our analyses demonstrate that neither human nor macaque aggression is unprovoked. Rather, both humans and macaques are responding to one another's behavior. Mitigation of human-primate conflict, and indeed other types of human-wildlife conflict in such coupled systems, will require a holistic investigation of the ways in which each participant is responding to, and consequently altering, the behavior of the other. © 2015 Wiley Periodicals, Inc.

A Foxp2 mutation implicated in human speech deficits alters sequencing of ultrasonic vocalizations in adult male mice

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Jonathan Chabout

2016-10-01

Full Text Available Development of proficient spoken language skills is disrupted by mutations of the FOXP2 transcription factor. A heterozygous missense mutation in the KE family causes speech apraxia, involving difficulty producing words with complex learned sequences of syllables. Manipulations in songbirds have helped to elucidate the role of this gene in vocal learning, but findings in non-human mammals have been limited or inconclusive. Here we performed a systematic study of ultrasonic vocalizations (USVs of adult male mice carrying the KE family mutation. Using novel statistical tools, we found that Foxp2 heterozygous mice did not have detectable changes in USV syllable acoustic structure, but produced shorter sequences and did not shift to more complex syntax in social contexts where wildtype animals did. Heterozygous mice also displayed a shift in the position of their rudimentary laryngeal motor cortex layer-5 neurons. Our findings indicate that although mouse USVs are mostly innate, the underlying contributions of FoxP2 to sequencing of vocalizations are conserved with humans.

Adult growth hormone deficiency

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Vishal Gupta

2011-01-01

Full Text Available Adult growth hormone deficiency (AGHD is being recognized increasingly and has been thought to be associated with premature mortality. Pituitary tumors are the commonest cause for AGHD. Growth hormone deficiency (GHD has been associated with neuropsychiatric-cognitive, cardiovascular, neuromuscular, metabolic, and skeletal abnormalities. Most of these can be reversed with growth hormone therapy. The insulin tolerance test still remains the gold standard dynamic test to diagnose AGHD. Growth hormone is administered subcutaneously once a day, titrated to clinical symptoms, signs and IGF-1 (insulin like growth factor-1. It is generally well tolerated at the low-doses used in adults. Pegylated human growth hormone therapy is on the horizon, with a convenient once a week dosing.

Ectopic Human Fasciola hepatica Infection by an Adult Worm in the Mesocolon.

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Kim, Ah Jin; Choi, Chang Hwan; Choi, Sun Keun; Shin, Yong Woon; Park, Yun-Kyu; Kim, Lucia; Choi, Suk Jin; Han, Jee Young; Kim, Joon Mee; Chu, Young Chae; Park, In Suh

2015-12-01

We report here an ectopic case of Fasciola hepatica infection confirmed by recovery of an adult worm in the mesocolon. A 56-year-old female was admitted to our hospital with discomfort and pain in the left lower quadrant of the abdomen. Abdominal CT showed 3 abscesses in the left upper quadrant, mesentery, and pelvic cavity. On surgical exploration, abscess pockets were found in the mesocolon of the sigmoid colon and transverse colon. A leaf-like worm found in the abscess pocket of the mesocolon of the left colon was diagnosed as an adult fluke of F. hepatica. Histologically, numerous eggs of F. hepatica were noted with acute and chronic granulomatous inflammations in the subserosa and pericolic adipose tissues. Conclusively, a rare case of ectopic fascioliasis has been confirmed in this study by the adult worm recovery of F. hepatica in the mesocolon.

Gene targeting in adult rhesus macaque fibroblasts

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Wolf Don P

2008-03-01

Full Text Available Abstract Background Gene targeting in nonhuman primates has the potential to produce critical animal models for translational studies related to human diseases. Successful gene targeting in fibroblasts followed by somatic cell nuclear transfer (SCNT has been achieved in several species of large mammals but not yet in primates. Our goal was to establish the protocols necessary to achieve gene targeting in primary culture of adult rhesus macaque fibroblasts as a first step in creating nonhuman primate models of genetic disease using nuclear transfer technology. Results A primary culture of adult male fibroblasts was transfected with hTERT to overcome senescence and allow long term in vitro manipulations. Successful gene targeting of the HPRT locus in rhesus macaques was achieved by electroporating S-phase synchronized cells with a construct containing a SV40 enhancer. Conclusion The cell lines reported here could be used for the production of null mutant rhesus macaque models of human genetic disease using SCNT technology. In addition, given the close evolutionary relationship and biological similarity between rhesus macaques and humans, the protocols described here may prove useful in the genetic engineering of human somatic cells.

Circuits regulating pleasure and happiness: the evolution of the amygdalar-hippocampal-habenular connectivity in vertebrates.

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Anton J.M. Loonen

2016-11-01

Full Text Available Appetitive-searching (reward-seeking and distress-avoiding (misery-fleeing behavior are essential for all free moving animals to stay alive and to have offspring. Therefore, even the oldest ocean-dwelling animal creatures, living about 560 million years ago and human ancestors, must have been capable of generating these behaviors. The current article describes the evolution of the forebrain with special reference to the development of the misery-fleeing system. Although the earliest vertebrate ancestor already possessed a dorsal pallium, which corresponds to the human neocortex, the structure and function of the neocortex was acquired quite recently within the mammalian evolutionary line. Up to, and including, amphibians, the dorsal pallium can be considered to be an extension of the medial pallium, which later develops into the hippocampus. The ventral and lateral pallium largely go up into the corticoid part of the amygdala. The striatopallidum of these early vertebrates becomes extended amygdala, consisting of centromedial amygdala (striatum connected with the bed nucleus of the stria terminalis (pallidum. This amygdaloid system gives output to hypothalamus and brainstem, but also a connection with the cerebral cortex exists, which in part was created after the development of the more recent cerebral neocortex. Apart from bidirectional connectivity with the hippocampal complex, this route can also be considered to be an output channel as the fornix connects the hippocampus with the medial septum, which is the most important input structure of the medial habenula. The medial habenula regulates the activity of midbrain structures adjusting the intensity of the misery-fleeing response. Within the bed nucleus of the stria terminalis the human homologue of the ancient lateral habenula-projecting globus pallidus may exist; this structure is important for the evaluation of efficacy of the reward-seeking response. The described organization offers a

In vitro and in vivo characterisation of nor-{beta}-CIT: a potential radioligand for visualisation of the serotonin transporter in the brain

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Bergstroem, K.A. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden)]|[Kuopio University Hospital, Clinical Physiology, FIN-70210 Kuopio (Finland); Halldin, C. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Hall, H. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Lundkvist, C. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Ginovart, N. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Swahn, C.G. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Farde, L. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden)

1997-06-10

Radiolabelled 2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)tropane ({beta}-CIT) has been used in clinical studies for the imaging of dopamine and serotonin transporters with single-photon emission tomography (SPET). 2{beta}-Carbomethoxy-3{beta}-(4-iodophenyl)nortropane (nor-{beta}-CIT) is a des-methyl analogue of {beta}-CIT, which in vitro has tenfold higher affinity (IC{sub 50}=0.36 nM) to the serotonin transporter than {beta}-CIT (IC{sub 50}=4.2 nM). Nor-{beta}-CIT may thus be a useful radioligand for imaging of the serotonin transporter. In the present study iodine-125 and carbon-11 labelled nor-{beta}-CIT were prepared for in vitro autoradiographic studies on post-mortem human brain cryosections and for in vivo positron emission tomography (PET) studies in Cynomolgus monkeys. Whole hemisphere autoradiography with [{sup 125}I]nor-{beta}-CIT demonstrated high binding in the striatum, the thalamus and cortical regions of the human brain. Addition of a high concentration (1 {mu}M) of citalopram inhibited binding in the thalamus and the neocortex, but not in the striatum. In PET studies with [{sup 11}C]nor-{beta}-CIT there was rapid uptake of radioactivity in the monkey brain (6% of injected dose at 15 min) and high accumulation of radioactivity in the striatum, thalamus and neocortex. Thalamus to cerebellum and cortex to cerebellum ratios were 2.5 and 1.8 at 60 min, respectively. The ratios obtained with [{sup 11}C]nor-{beta}-CIT were 20%-40% higher than those previously obtained with [{sup 11}C]{beta}-CIT. Radioactivity in the thalamus and the neocortex but not in the striatum was displaceable with citalopram (5 mg/kg). In conclusion, nor-{beta}-CIT binds to the serotonin transporter in the primate brain in vitro and in vivo and has potential for PET and SPET imaging of the serotonin transporter in human brain. (orig.). With 4 figs.

Strategies for human-driven robot comprehension of spatial descriptions by older adults in a robot fetch task.

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Carlson, Laura; Skubic, Marjorie; Miller, Jared; Huo, Zhiyu; Alexenko, Tatiana

2014-07-01

This contribution presents a corpus of spatial descriptions and describes the development of a human-driven spatial language robot system for their comprehension. The domain of application is an eldercare setting in which an assistive robot is asked to "fetch" an object for an elderly resident based on a natural language spatial description given by the resident. In Part One, we describe a corpus of naturally occurring descriptions elicited from a group of older adults within a virtual 3D home that simulates the eldercare setting. We contrast descriptions elicited when participants offered descriptions to a human versus robot avatar, and under instructions to tell the addressee how to find the target versus where the target is. We summarize the key features of the spatial descriptions, including their dynamic versus static nature and the perspective adopted by the speaker. In Part Two, we discuss critical cognitive and perceptual processing capabilities necessary for the robot to establish a common ground with the human user and perform the "fetch" task. Based on the collected corpus, we focus here on resolving the perspective ambiguity and recognizing furniture items used as landmarks in the descriptions. Taken together, the work presented here offers the key building blocks of a robust system that takes as input natural spatial language descriptions and produces commands that drive the robot to successfully fetch objects within our eldercare scenario. Copyright © 2014 Cognitive Science Society, Inc.

Higher Prevalence of Human Papillomavirus Infection in Adolescent and Young Adult Girls Belonging to Different Indian Tribes with Varied Socio-Sexual Lifestyle

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Sharma, Kirti; Kathait, Atul; Jain, Asha; Kujur, Karmila; Raghuwanshi, Shirish; Bharti, Alok Chandra; Saklani, Asha Chandola; Das, Bhudev Chandra

2015-01-01

Background Despite high prevalence of human papillomavirus (HPV) infection and cervical cancer in Indian women, no study has been done in tribal populations whose socio-sexual lifestyle is different. Therefore, HPV screening has been carried out in pre-adolescent, adolescent and young adult tribal girls using self-collected urine samples. Methods 20–35 ml self-collected midstream urine samples were obtained from a total of 2278 healthy tribal girls (9–25 years) comprising pre-adolescent, adolescent and young adults from three Indian states: Madhya Pradesh, Jharkhand and Chhattisgarh. β-globin positive 2034 samples were employed for HPV detection and genotyping. Results The overall prevalence of HPV infection in tribal girls was 12.9% (262/2034). More than 65% (172/262) of them were infected with HR-HPV types of which HPV16 was the most predominant type (54%). Young adult girls aged 18–25 years showed a significantly higher prevalence of HPV infection (19.2%; OR = 3.36; 95% CI 2.97–6.34, P<0.001) as compared to that in adolescent (11.4%; OR = 1.82; 95% CI 1.20–2.76, P<0.01) or pre-adolescent girls (6.6%). Conclusion This is a first study showing significantly a very high prevalence of HPV infection in adolescent and young adult tribal girls possibly due to different socio-sexual behavior, indicating a serious health concern for Indian tribal women. PMID:25954813

Peripheral Nerve Injury in Developing Rats Reorganizes Representation Pattern in Motor Cortex

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Donoghue, John P.; Sanes, Jerome N.

1987-02-01

We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stimuli activated shoulder and trunk muscles in experimental animals. In addition, an expanded cortical representation of intact body parts was present and there was an absence of a distinct portion of motor cortex. These data demonstrate that representation patterns in motor cortex can be altered by peripheral nerve injury during development.

ADVANCED ADULT EDUCATION IN ISRAEL.

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Ministry of Education and Culture, Jerusalem (Israel).

ADULT EDUCATION IN ISRAEL IS UNDER THE SUPERVISION OF THE CULTURAL DEPARTMENT, WHICH RECOMMENDS TEACHERS AND LECTURERS AND IS RESPONSIBLE FOR INSPECTION AND FINANCIAL SUPPORT. STUDENT FEES ARE COLLECTED LOCALLY. PREVIOUSLY DEVOTED TO JEWISH TOPICS AND HEBREW LANGUAGE, THE PROGRAM HAS BEEN EXPANDED TO INCLUDE FORMAL SECONDARY EDUCATION, HUMANITIES,…

Functional imaging of numerical processing in adults and 4-y-old children.

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Jessica F Cantlon

2006-05-01

Full Text Available Adult humans, infants, pre-school children, and non-human animals appear to share a system of approximate numerical processing for non-symbolic stimuli such as arrays of dots or sequences of tones. Behavioral studies of adult humans implicate a link between these non-symbolic numerical abilities and symbolic numerical processing (e.g., similar distance effects in accuracy and reaction-time for arrays of dots and Arabic numerals. However, neuroimaging studies have remained inconclusive on the neural basis of this link. The intraparietal sulcus (IPS is known to respond selectively to symbolic numerical stimuli such as Arabic numerals. Recent studies, however, have arrived at conflicting conclusions regarding the role of the IPS in processing non-symbolic, numerosity arrays in adulthood, and very little is known about the brain basis of numerical processing early in development. Addressing the question of whether there is an early-developing neural basis for abstract numerical processing is essential for understanding the cognitive origins of our uniquely human capacity for math and science. Using functional magnetic resonance imaging (fMRI at 4-Tesla and an event-related fMRI adaptation paradigm, we found that adults showed a greater IPS response to visual arrays that deviated from standard stimuli in their number of elements, than to stimuli that deviated in local element shape. These results support previous claims that there is a neurophysiological link between non-symbolic and symbolic numerical processing in adulthood. In parallel, we tested 4-y-old children with the same fMRI adaptation paradigm as adults to determine whether the neural locus of non-symbolic numerical activity in adults shows continuity in function over development. We found that the IPS responded to numerical deviants similarly in 4-y-old children and adults. To our knowledge, this is the first evidence that the neural locus of adult numerical cognition takes form early in

Visual advantage in deaf adults linked to retinal changes.

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Charlotte Codina

Full Text Available The altered sensory experience of profound early onset deafness provokes sometimes large scale neural reorganisations. In particular, auditory-visual cross-modal plasticity occurs, wherein redundant auditory cortex becomes recruited to vision. However, the effect of human deafness on neural structures involved in visual processing prior to the visual cortex has never been investigated, either in humans or animals. We investigated neural changes at the retina and optic nerve head in profoundly deaf (N = 14 and hearing (N = 15 adults using Optical Coherence Tomography (OCT, an in-vivo light interference method of quantifying retinal micro-structure. We compared retinal changes with behavioural results from the same deaf and hearing adults, measuring sensitivity in the peripheral visual field using Goldmann perimetry. Deaf adults had significantly larger neural rim areas, within the optic nerve head in comparison to hearing controls suggesting greater retinal ganglion cell number. Deaf adults also demonstrated significantly larger visual field areas (indicating greater peripheral sensitivity than controls. Furthermore, neural rim area was significantly correlated with visual field area in both deaf and hearing adults. Deaf adults also showed a significantly different pattern of retinal nerve fibre layer (RNFL distribution compared to controls. Significant correlations between the depth of the RNFL at the inferior-nasal peripapillary retina and the corresponding far temporal and superior temporal visual field areas (sensitivity were found. Our results show that cross-modal plasticity after early onset deafness may not be limited to the sensory cortices, noting specific retinal adaptations in early onset deaf adults which are significantly correlated with peripheral vision sensitivity.

No association between cumulative traumatic experiences and sex in risk for posttraumatic stress disorder among human immunodeficiency virus-positive adults.

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Morris, Tanya; Naidoo, Pamela; Cloete, Karen J; Harvey, Justin; Seedat, Soraya

2013-06-01

This study examined the association between the type and number of traumatic experiences and the conditional risk for posttraumatic stress disorder (PTSD), stratified by sex, in human immunodeficiency virus (HIV). We evaluated 465 (114 male and 350 female) HIV-positive adults attending HIV clinics in Cape Town, South Africa. Demographic and clinical data were collected, and the participants were screened for current PTSD and traumatic event exposure using the Mini-International Neuropsychiatric Interview and the Life Events Checklist, respectively. The highest attributable risk for PTSD was derived from sexual assault (17.4%) and transport accidents (16.9%). Only sexual assault was significantly (p = 0.002) associated with current PTSD. Although sex had no effect on the prediction of current PTSD, HIV-infected men tended to experience more lifetime traumas than HIV-infected women, with the men having significantly higher rates of exposure than women to physical assault (p = 0.018) and assault with a weapon (p = 0.001). These data highlight the importance of considering trauma type in contributing to the burden of PTSD in HIV-infected adults.

Two distinct genes for ADP/ATP translocase are expressed at the mRNA level in adult human liver

International Nuclear Information System (INIS)

Houldsworth, J.; Attardi, G.

1988-01-01

Several clones hybridizing with a bovine ADP/ATP translocase cDNA were isolated from an adult human liver cDNA library in the vector pEX1. DNA sequence analysis revealed that these clones encode two distinct forms of translocase. In particular, two clones specifying the COOH-end-proximal five-sixths of the protein exhibit a 9% amino acid sequence divergence and totally dissimilar 3' untranslated regions. One of these cDNAs is nearly identical in sequence to an ADP/ATP translocase clone (hp2F1) recently isolated from a human fibroblast cDNA library with three amino acid changes and a few differences in the 3' untranslated region. Another clone isolated from the pEX1 library contains a reading frame encoding the remaining, NH 2 -end-proximal, 37 amino acids of the translocase. This sequence differs significantly (14% amino acid sequence divergence) from the corresponding segment of hp2F1, and the 5' untranslated regions of the two clones are totally dissimilar. RNA transfer hybridization experiments utilizing the clones isolated from the pEX1 library revealed the presence in HeLa cells of three distinct mRNA species. The pattern of hybridization and the sizes of these mRNAs suggest a greater complexity of organization and expression of the ADP/ATP translocase genes in human cells than indicated by the analysis of the cDNA clones

NOHSS Adult Indicators - 2010 And Prior BRFSS

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U.S. Department of Health & Human Services — Data from BRFSS for indicators of adult oral health for 1999 and even years from 2002 through 2010. National estimates are represented by the median prevalence among...

Modularity, comparative cognition and human uniqueness.

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Shettleworth, Sara J

2012-10-05

Darwin's claim 'that the difference in mind between man and the higher animals … is certainly one of degree and not of kind' is at the core of the comparative study of cognition. Recent research provides unprecedented support for Darwin's claim as well as new reasons to question it, stimulating new theories of human cognitive uniqueness. This article compares and evaluates approaches to such theories. Some prominent theories propose sweeping domain-general characterizations of the difference in cognitive capabilities and/or mechanisms between adult humans and other animals. Dual-process theories for some cognitive domains propose that adult human cognition shares simple basic processes with that of other animals while additionally including slower-developing and more explicit uniquely human processes. These theories are consistent with a modular account of cognition and the 'core knowledge' account of children's cognitive development. A complementary proposal is that human infants have unique social and/or cognitive adaptations for uniquely human learning. A view of human cognitive architecture as a mosaic of unique and species-general modular and domain-general processes together with a focus on uniquely human developmental mechanisms is consistent with modern evolutionary-developmental biology and suggests new questions for comparative research.

The presence and absence of lymphatic vessels in the adult human intervertebral disc: relation to disc pathology

International Nuclear Information System (INIS)

Kliskey, Karolina; Williams, Kelly; Yu, J.; Urban, Jill; Athanasou, Nick; Jackson, David

2009-01-01

Although the normal adult human intervertebral disc is considered to be avascular, vascularised cellular fibrous tissue can be found in pathological conditions involving the disc such as disc herniation. Whether lymphatics vessels form a component of this reparative tissue is not known as the presence or absence of lymphatics in herniated and normal disc tissue is not known. We examined spinal tissues and discectomy specimens for the presence of lymphatics. The examination used immunohistochemistry to identify the specific lymphatic endothelial cell markers, podoplanin and LYVE1. Lymphatic vessels were not found in the nucleus pulposus or annulus fibrosus of intact, non-herniated lumbar and thoracic discs but were present in the surrounding ligaments. Ingrowth of fibrous tissue was seen in 73% of herniated disc specimens of which 36% contained LYVE1+/podoplanin + lymphatic vessels. Lymphatic vessels were not seen in the sacrum and coccyx or biopsies of four sacrococcygeal chordomas, but they were noted in surrounding extra-osseous fat and fibrous tissue at the edge of the infiltrating tumour. Our findings indicate that lymphatic vessels are not present in the normal adult intervertebral disc but that, when there is extrusion of disc material into surrounding soft tissue, there is ingrowth of reparative fibrous tissue containing lymphatic vessels. Our findings also indicate that chordoma, a tumour of notochordal origin, spreads to regional lymph nodes via lymphatics in para-spinal soft tissues. (orig.)

The HIV-1 viral protein Tat increases glutamate and decreases GABA exocytosis from human and mouse neocortical nerve endings.

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Musante, Veronica; Summa, Maria; Neri, Elisa; Puliti, Aldamaria; Godowicz, Tomasz T; Severi, Paolo; Battaglia, Giuseppe; Raiteri, Maurizio; Pittaluga, Anna

2010-08-01

Human immunodeficiency virus-1 (HIV-1)-encoded transactivator of transcription (Tat) potentiated the depolarization-evoked exocytosis of [(3)H]D-aspartate ([(3)H]D-ASP) from human neocortical terminals. The metabotropic glutamate (mGlu) 1 receptor antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) prevented this effect, whereas the mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP) was ineffective. Western blot analysis showed that human neocortex synaptosomes possess mGlu1 and mGlu5 receptors. Tat potentiated the K(+)-evoked release of [(3)H]D-ASP or of endogenous glutamate from mouse neocortical synaptosomes in a CPCCOEt-sensitive and MPEP-insensitive manner. Deletion of mGlu1 receptors (crv4/crv4 mice) or mGlu5 receptors (mGlu5(-/-)mouse) silenced Tat effects. Tat enhanced inositol 1,4,5-trisphosphate production in human and mouse neocortical synaptosomes, consistent with the involvement of group I mGlu receptors. Tat inhibited the K(+)-evoked release of [(3)H]gamma-aminobutyric acid ([(3)H]GABA) from human synaptosomes and that of endogenous GABA or [(3)H]GABA from mouse nerve terminals; the inhibition was insensitive to CPCCOEt or MPEP. Tat-induced effects were retained by Tat(37-72) but not by Tat(48-85). In mouse neocortical slices, Tat facilitated the K(+)- and the veratridine-induced release of [(3)H]D-ASP in a CPCCOEt-sensitive manner and was ineffective in crv4/crv4 mouse slices. These observations are relevant to the comprehension of the pathophysiological effects of Tat in central nervous system and may suggest new potential therapeutic approaches to the cure of HIV-1-associated dementia.

Hesperetin induces melanin production in adult human epidermal melanocytes.

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Usach, Iris; Taléns-Visconti, Raquel; Magraner-Pardo, Lorena; Peris, José-Esteban

2015-06-01

One of the major sources of flavonoids for humans are citrus fruits, hesperidin being the predominant flavonoid. Hesperetin (HSP), the aglycon of hesperidin, has been reported to provide health benefits such as antioxidant, anti-inflammatory and anticarcinogenic effects. However, the effect of HSP on skin pigmentation is not clear. Some authors have found that HSP induces melanogenesis in murine B16-F10 melanoma cells, which, if extrapolated to in vivo conditions, might protect skin against photodamage. Since the effect of HSP on normal melanocytes could be different to that observed on melanoma cells, the described effect of HSP on murine melanoma cells has been compared to the effect obtained using normal human melanocytes. HSP concentrations of 25 and 50 µM induced melanin synthesis and tyrosinase activity in human melanocytes in a concentration-dependent manner. Compared to control melanocytes, 25 µM HSP increased melanin production and tyrosinase activity 1.4-fold (p melanin production in human melanocyte cultures could be reproduced on human skin. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human Adult Stem Cells Maintain a Constant Phenotype Profile Irrespective of Their Origin, Basal Media, and Long Term Cultures

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Indumathi Somasundaram

2015-01-01

Full Text Available The study aims to identify the phenotypic marker expressions of different human adult stem cells derived from, namely, bone marrow, subcutaneous fat, and omentum fat, cultured in different media, namely, DMEM-Low Glucose, Alpha-MEM, DMEM-F12 and DMEM-KO and under long term culture conditions (>P20. We characterized immunophenotype by using various hematopoietic, mesenchymal, endothelial markers, and cell adhesion molecules in the long term cultures (Passages-P1, P3, P5, P9, P12, P15, and P20. Interestingly, data revealed similar marker expression profiles irrespective of source, basal media, and extensive culturing. This demonstrates that all adult stem cell sources mentioned in this study share similar phenotypic marker and all media seem appropriate for culturing these sources. However, a disparity was observed in the markers such as CD49d, CD54, CD117, CD29, and CD106, thereby warranting further research on these markers. Besides the aforesaid objective, it is understood from the study that immunophenotyping acts as a valuable tool to identify inherent property of each cell, thereby leading to a valuable cell based therapy.

Maturation of the limbic system revealed by MR FLAIR imaging

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Schneider, Jacques F.; Vergesslich, Klara [University Children' s Hospital UKBB, Department of Paediatric Radiology, Basel (Switzerland)

2007-04-15

Cortical signal intensity (SI) of the limbic system in adults is known to be higher than in neocortical structures, but time-related changes in SI during childhood have not been described. To detect maturation-related SI changes within the limbic system using a fluid-attenuated inversion recovery (FLAIR) MR sequence. Twenty children (10 boys, 10 girls; age 3.5-18 years, mean 11.2 years) with no neurological abnormality and normal MR imaging examination were retrospectively selected. On two coronal FLAIR slices, ten regions of interest (ROI) with a constant area of 10 mm{sup 2} were manually placed in the archeocortex (hippocampus), periarcheocortex (parahippocampal gyrus, subcallosal area, cingulate gyrus) and in the neocortex at the level of the superior frontal gyrus on both sides. Significant SI gradients were observed with a higher intensity in the archeocortex, intermediate intensity in the periarcheocortex and low intensity in the neocortex. Significant higher SI values in hippocampal and parahippocampal structures were detected in children up to 10 years of age. These differences mainly reflected differences in cortical structure and myelination state. Archeocortical structures especially showed significant age-related intensity progression suggesting ongoing organization and/or myelination until early adolescence. (orig.)

Maturation of the limbic system revealed by MR FLAIR imaging

International Nuclear Information System (INIS)

Schneider, Jacques F.; Vergesslich, Klara

2007-01-01

Cortical signal intensity (SI) of the limbic system in adults is known to be higher than in neocortical structures, but time-related changes in SI during childhood have not been described. To detect maturation-related SI changes within the limbic system using a fluid-attenuated inversion recovery (FLAIR) MR sequence. Twenty children (10 boys, 10 girls; age 3.5-18 years, mean 11.2 years) with no neurological abnormality and normal MR imaging examination were retrospectively selected. On two coronal FLAIR slices, ten regions of interest (ROI) with a constant area of 10 mm 2 were manually placed in the archeocortex (hippocampus), periarcheocortex (parahippocampal gyrus, subcallosal area, cingulate gyrus) and in the neocortex at the level of the superior frontal gyrus on both sides. Significant SI gradients were observed with a higher intensity in the archeocortex, intermediate intensity in the periarcheocortex and low intensity in the neocortex. Significant higher SI values in hippocampal and parahippocampal structures were detected in children up to 10 years of age. These differences mainly reflected differences in cortical structure and myelination state. Archeocortical structures especially showed significant age-related intensity progression suggesting ongoing organization and/or myelination until early adolescence. (orig.)

A Multispecies Approach to Co-Sleeping : Integrating Human-Animal Co-Sleeping Practices into Our Understanding of Human Sleep.

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Smith, Bradley P; Hazelton, Peta C; Thompson, Kirrilly R; Trigg, Joshua L; Etherton, Hayley C; Blunden, Sarah L

2017-09-01

Human sleeping arrangements have evolved over time and differ across cultures. The majority of adults share their bed at one time or another with a partner or child, and many also sleep with pets. In fact, around half of dog and cat owners report sharing a bed or bedroom with their pet(s). However, interspecies co-sleeping has been trivialized in the literature relative to interpersonal or human-human co-sleeping, receiving little attention from an interdisciplinary psychological perspective. In this paper, we provide a historical outline of the "civilizing process" that has led to current sociocultural conceptions of sleep as an individual, private function crucial for the functioning of society and the health of individuals. We identify similar historical processes at work in the formation of contemporary constructions of socially normative sleeping arrangements for humans and animals. Importantly, since previous examinations of co-sleeping practices have anthropocentrically framed this topic, the result is an incomplete understanding of co-sleeping practices. By using dogs as an exemplar of human-animal co-sleeping, and comparing human-canine sleeping with adult-child co-sleeping, we determine that both forms of co-sleeping share common factors for establishment and maintenance, and often result in similar benefits and drawbacks. We propose that human-animal and adult-child co-sleeping should be approached as legitimate and socially relevant forms of co-sleeping, and we recommend that co-sleeping be approached broadly as a social practice involving relations with humans and other animals. Because our proposition is speculative and derived from canine-centric data, we recommend ongoing theoretical refinement grounded in empirical research addressing co-sleeping between humans and multiple animal species.

Adult-type hypolactasia and regulation of lactase expression

DEFF Research Database (Denmark)

Troelsen, Jesper Thorvald

2005-01-01

, the main carbohydrate in milk. Individuals with adult-type hypolactasia lose their lactase expression before adulthood and consequently often become lactose intolerant with associated digestive problems (e.g. diarrhoea). In contrast, lactase persistent individuals have a lifelong lactase expression......A common genetically determined polymorphism in the human population leads to two distinct phenotypes in adults, lactase persistence and adult-type hypolactasia (lactase non-persistence). All healthy newborn children express high levels of lactase and are able to digest large quantities of lactose...... and are able to digest lactose as adults. Lactase persistence can be regarded as the mutant phenotype since other mammals down-regulate their lactase expression after weaning (the postweaning decline). This phenomenon does not occur in lactase persistent individuals. The regulation of lactase expression...

Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later

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Bond, Allison M.; Ming, Guo-li; Song, Hongjun

2015-01-01

Summary Adult somatic stem cells in various organs maintain homeostatic tissue regeneration and enhance plasticity. Since its initial discovery five decades ago, investigations of adult neurogenesis and neural stem cells have led to an established and expanding field that has significantly influenced many facets of neuroscience, developmental biology and regenerative medicine. Here we review recent progress and focus on questions related to adult mammalian neural stem cells that also apply to other somatic stem cells. We further discuss emerging topics that are guiding the field toward better understanding adult neural stem cells and ultimately applying these principles to improve human health. PMID:26431181

A concept analysis of dignity for older adults.

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Jacelon, Cynthia S; Connelly, Thomas W; Brown, Rana; Proulx, Kathy; Vo, Thuy

2004-10-01

Human dignity is an essential value of professional nursing education as well as a component of the American Nurses Association Code of Ethics. Nurses are exhorted to treat patients with dignity, and older adults want to be treated with dignity and die with dignity. Although dignity, particularly the dignity of older adults, is often discussed in the health care literature, its meaning is not always clear. The aim of this paper is to describe a concept analysis to develop a definition of dignity in older adults. Data were collected using a literature review and five focus groups composed of older adults. The literature provided data about professionals' ideas of dignity and the focus groups provided qualitative data about the nature of dignity in older people. The literature review and focus groups were carried out concurrently, followed by synthesis of the findings. Dignity is an inherent characteristic of being human, it can be subjectively felt as an attribute of the self, and is made manifest through behaviour that demonstrates respect for self and others. Dignity must be learned, and an individual's dignity is affected by the treatment received from others. A behavioural definition of dignity was constructed and this could provide the theoretical basis for nurses to develop interventions that foster dignity for older people.

The robustness of diagnostic tests for GH deficiency in adults

DEFF Research Database (Denmark)

Andersen, Marianne

2015-01-01

with recombinant human GH. There is, however, an ongoing debate on how to diagnose GHD, especially in adults. A GH response below the cut-off limit of a GH-stimulation test is required in most cases for establishing GHD in adults. No 'gold standard' GH-stimulation test exists, but some GH stimulation tests may...

Two classes of astrocytes in the adult human and pig retina in terms of their expression of high affinity NGF receptor (TrkA).

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Ruiz-Ederra, Javier; Hitchcock, Peter F; Vecino, Elena

2003-02-13

Astrocytes have been implicated in axon guidance and synaptic regeneration in the retina and these processes involve activation of the high affinity nerve growth factor receptor, known as the tyrosine kinase A (TrkA) receptor. The purpose of the present study was to characterize the expression of TrkA in astrocytes of the adult pig and human retina. To this end, sections of human and pig retinas were immunolabeled with a combination of antibodies to glial fibrillary acidic protein (GFAP) and TrkA. Our study revealed that most of the GFAP-positive cells express TrkA, whereas a rare, novel subpopulation of astrocytes was found to be devoid of TrkA. Our results support the idea that astrocytes play an important neurotrophic role in the retina.

Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms.

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Svingen, T; Jørgensen, A; Rajpert-De Meyts, E

2014-08-01

The measurement of gene expression levels in cells and tissues typically depends on a suitable point of reference for inferring biological relevance. For quantitative (or real-time) RT-PCR assays, the method of choice is often to normalize gene expression data to an endogenous gene that is stably expressed across the samples analysed: a so-called normalizing or housekeeping gene. Although this is a valid strategy, the identification of stable normalizing genes has proved challenging and a gene showing stable expression across all cells or tissues is unlikely to exist. Therefore, it is necessary to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further recommend that such studies should be accompanied by additional assessment of histology and cellularity of each sample. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Adipose-derived adult stem cells: available technologies for potential clinical regenerative applications in dentistry.

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Catalano, Enrico; Cochis, Andrea; Varoni, Elena; Rimondini, Lia; Carrassi, Antonio; Azzimonti, Barbara

2013-01-01

Tissue homeostasis depends closely on the activity and welfare of adult stem cells. These cells represent a promising tool for biomedical research since they can aid in treatment and promote the regeneration of damaged organs in many human disorders. Adult stem cells indefinitely preserve their ability to self-renew and differentiate into various phenotypes; this capacity could be promoted in vitro by particular culture conditions (differentiation media) or spontaneously induced in vivo by exploiting the biochemical and mechanical properties of the tissue in which the stem cells are implanted. Among the different sources of adult stem cells, adipose tissue is an attractive possibility thanks to its ready availability and the standard extraction techniques at our disposal today. This review discusses the isolation, characterization, and differentiation of human adipose-derived adult stem cells, as well as regeneration strategies, therapeutic uses, and adverse effects of their delivery. In particular, since oral disorders (e.g., trauma, erosion, and chronic periodontitis) often cause the loss of dental tissue along with functional, phonetic, and aesthetic impairment, this review focuses on the application of human adipose-derived adult stem cells, alone or in combination with biomaterials, in treating oral diseases.

Human parvovirus PARV4 DNA in tissues from adult individuals: a comparison with human parvovirus B19 (B19V

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Rotellini Matteo

2010-10-01

Full Text Available Abstract Background PARV4 is a new member of the Parvoviridae family not closely related to any of the known human parvoviruses. Viremia seems to be a hallmark of PARV4 infection and viral DNA persistence has been demonstrated in a few tissues. Till now, PARV4 has not been associated with any disease and its prevalence in human population has not been clearly established. This study was aimed to assess the tissue distribution and the ability to persist of PARV4 in comparison to parvovirus B19 (B19V. Results PARV4 and B19V DNA detection was carried out in various tissues of individuals without suspect of acute viral infection, by a real time PCR and a nested PCR, targeting the ORF2 and the ORF1 respectively. Low amount of PARV4 DNA was found frequently (>40% in heart and liver of adults individuals, less frequently in lungs and kidneys (23,5 and 18% respectively and was rare in bone marrow, skin and synovium samples (5,5%, 4% and 5%, respectively. By comparison, B19V DNA sequences were present in the same tissues with a higher frequency (significantly higher in myocardium, skin and bone marrow except than in liver where the frequency was the same of PARV4 DNA and in plasma samples where B19V frequency was significantly lower than that of PARV4 Conclusions The particular tropism of PARV4 for liver and heart, here emerged, suggests to focus further studies on these tissues as possible target for viral replication and on the possible role of PARV4 infection in liver and heart diseases. Neither bone marrow nor kidney seem to be a common target of viral replication.

A Western diet ecological module identified from the 'humanized' mouse microbiota predicts diet in adults and formula feeding in children.

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Siddharth, Jay; Holway, Nicholas; Parkinson, Scott J

2013-01-01

The interplay between diet and the microbiota has been implicated in the growing frequency of chronic diseases associated with the Western lifestyle. However, the complexity and variability of microbial ecology in humans and preclinical models has hampered identification of the molecular mechanisms underlying the association of the microbiota in this context. We sought to address two key questions. Can the microbial ecology of preclinical models predict human populations? And can we identify underlying principles that surpass the plasticity of microbial ecology in humans? To do this, we focused our study on diet; perhaps the most influential factor determining the composition of the gut microbiota. Beginning with a study in 'humanized' mice we identified an interactive module of 9 genera allied with Western diet intake. This module was applied to a controlled dietary study in humans. The abundance of the Western ecological module correctly predicted the dietary intake of 19/21 top and 21/21 of the bottom quartile samples inclusive of all 5 Western and 'low-fat' diet subjects, respectively. In 98 volunteers the abundance of the Western module correlated appropriately with dietary intake of saturated fatty acids, fat-soluble vitamins and fiber. Furthermore, it correlated with the geographical location and dietary habits of healthy adults from the Western, developing and third world. The module was also coupled to dietary intake in children (and piglets) correlating with formula (vs breast) feeding and associated with a precipitous development of the ecological module in young children. Our study provides a conceptual platform to translate microbial ecology from preclinical models to humans and identifies an ecological network module underlying the association of the gut microbiota with Western dietary habits.

A Western diet ecological module identified from the 'humanized' mouse microbiota predicts diet in adults and formula feeding in children.

Directory of Open Access Journals (Sweden)

Jay Siddharth

Full Text Available The interplay between diet and the microbiota has been implicated in the growing frequency of chronic diseases associated with the Western lifestyle. However, the complexity and variability of microbial ecology in humans and preclinical models has hampered identification of the molecular mechanisms underlying the association of the microbiota in this context. We sought to address two key questions. Can the microbial ecology of preclinical models predict human populations? And can we identify underlying principles that surpass the plasticity of microbial ecology in humans? To do this, we focused our study on diet; perhaps the most influential factor determining the composition of the gut microbiota. Beginning with a study in 'humanized' mice we identified an interactive module of 9 genera allied with Western diet intake. This module was applied to a controlled dietary study in humans. The abundance of the Western ecological module correctly predicted the dietary intake of 19/21 top and 21/21 of the bottom quartile samples inclusive of all 5 Western and 'low-fat' diet subjects, respectively. In 98 volunteers the abundance of the Western module correlated appropriately with dietary intake of saturated fatty acids, fat-soluble vitamins and fiber. Furthermore, it correlated with the geographical location and dietary habits of healthy adults from the Western, developing and third world. The module was also coupled to dietary intake in children (and piglets correlating with formula (vs breast feeding and associated with a precipitous development of the ecological module in young children. Our study provides a conceptual platform to translate microbial ecology from preclinical models to humans and identifies an ecological network module underlying the association of the gut microbiota with Western dietary habits.

The biorhythm of human skeletal growth.

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Mahoney, Patrick; Miszkiewicz, Justyna J; Chapple, Simon; Le Luyer, Mona; Schlecht, Stephen H; Stewart, Tahlia J; Griffiths, Richard A; Deter, Chris; Guatelli-Steinberg, Debbie

2018-01-01

Evidence of a periodic biorhythm is retained in tooth enamel in the form of Retzius lines. The periodicity of Retzius lines (RP) correlates with body mass and the scheduling of life history events when compared between some mammalian species. The correlation has led to the development of the inter-specific Havers-Halberg oscillation (HHO) hypothesis, which holds great potential for studying aspects of a fossil species biology from teeth. Yet, our understanding of if, or how, the HHO relates to human skeletal growth is limited. The goal here is to explore associations between the biorhythm and two hard tissues that form at different times during human ontogeny, within the context of the HHO. First, we investigate the relationship of RP to permanent molar enamel thickness and the underlying daily rate that ameloblasts secrete enamel during childhood. Following this, we develop preliminary research conducted on small samples of adult human bone by testing associations between RP, adult femoral length (as a proxy for attained adult stature) and cortical osteocyte lacunae density (as a proxy for the rate of osteocyte proliferation). Results reveal RP is positively correlated with enamel thickness, negatively correlated with femoral length, but weakly associated with the rate of enamel secretion and osteocyte proliferation. These new data imply that a slower biorhythm predicts thicker enamel for children but shorter stature for adults. Our results develop the intra-specific HHO hypothesis suggesting that there is a common underlying systemic biorhythm that has a role in the final products of human enamel and bone growth. © 2017 Anatomical Society.

Analysis of NR3A receptor subunits in human native NMDA receptors

DEFF Research Database (Denmark)

Nilsson, Anna; Eriksson, Maria; Muly, E Chris

2007-01-01

NR3A, representing the third class of NMDA receptor subunits, was first studied in rats, demonstrating ubiquitous expression in the developing central nervous system (CNS), but in the adult mainly expressed in spinal cord and some forebrain nuclei. Subsequent studies showed that rodent and non-human...... primate NR3A expression differs. We have studied the distribution of NR3A in the human CNS and show a widespread distribution of NR3A protein in adult human brain. NR3A mRNA and protein were found in all regions of the cerebral cortex, and also in the subcortical forebrain, midbrain and hindbrain. Only...... very low levels of NR3A mRNA and protein could be detected in homogenized adult human spinal cord, and in situ hybridization showed that expression was limited to ventral motoneurons. We found that NR3A is associated with NR1, NR2A and NR2B in adult human CNS, suggesting the existence of native NR1-NR2...

Gene structure of CYP3A4, an adult-specific form of cytochrome P450 in human livers, and its transcriptional control.

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Hashimoto, H; Toide, K; Kitamura, R; Fujita, M; Tagawa, S; Itoh, S; Kamataki, T

1993-12-01

CYP3 A4 is the adult-specific form of cytochrome P450 in human livers [Komori, M., Nishio, K., Kitada, M., Shiramatsu, K., Muroya, K., Soma, M., Nagashima, K. & Kamataki, T. (1990) Biochemistry 29, 4430-4433]. The sequences of three genomic clones for CYP3A4 were analyzed for all exons, exon-intron junctions and the 5'-flanking region from the major transcription site to nucleotide position -1105, and compared with those of the CYP3A7 gene, a fetal-specific form of cytochrome P450 in humans. The results showed that the identity of 5'-flanking sequences between CYP3A4 and CYP3A7 genes was 91%, and that each 5'-flanking region had characteristic sequences termed as NFSE (P450NF-specific element) and HFLaSE (P450HFLa specific element), respectively. A basic transcription element (BTE) also lay in the 5'-flanking region of the CYP3A4 gene as seen in many CYP genes [Yanagida, A., Sogawa, K., Yasumoto, K. & Fujii-Kuriyama, Y. (1990) Mol. Cell. Biol. 10, 1470-1475]. The BTE binding factor (BTEB) was present in both adult and fetal human livers. To examine the transcriptional activity of the CYP3A4 gene, DNA fragments in the 5'-flanking region of the gene were inserted in front of the simian virus 40 promoter and the chloramphenicol acetyltransferase structural gene, and the constructs were transfected in HepG2 cells. The analysis of the chloramphenicol acetyltransferase activity indicated that (a) specific element(s) which could bind with a factor(s) in livers was present in the 5'-flanking region of the CYP3A4 gene to show the transcriptional activity.

A Comprehensive Atlas of the Adult Mouse Penis

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Phillips, Tiffany R.; Wright, David K.; Gradie, Paul E.; Johnston, Leigh A.; Pask, Andrew J.

2016-01-01

Mice are routinely used to study the development of the external genitalia and, in particular, the process of male urethral closure. This is because misplacement of the male penile urethra, or hypospadias, is amongst the most common birth defects reported in humans. While mice present a tractable model to study penile development, several structures differ between mice and humans, and there is a lack of consensus in the literature on their annotation and developmental origins. Defining the ontology of the mouse prepuce is especially important for the relevance and interpretation of mouse models of hypospadias to human conditions. We have developed a detailed annotation of the adult mouse penis that addresses these differences and enables an accurate comparison of murine and human hypospadias phenotypes. Through MRI data, gross morphology and section histology, we define the origin of the mouse external and internal prepuces, their relationship to the single human foreskin as well as provide a comprehensive view of the various structures of the mouse penis and their associated muscle attachments within the body. These data are combined to annotate structures in a novel 3D adult penis atlas that can be downloaded, viewed at any angle, and manipulated to examine the relationship of various structures. PMID:26112156

A brief review on the use of functional near-infrared spectroscopy (fNIRS) for language imaging studies in human newborns and adults.

Science.gov (United States)

Quaresima, Valentina; Bisconti, Silvia; Ferrari, Marco

2012-05-01

Upon stimulation, real time maps of cortical hemodynamic responses can be obtained by non-invasive functional near-infrared spectroscopy (fNIRS) which measures changes in oxygenated and deoxygenated hemoglobin after positioning multiple sources and detectors over the human scalp. The current commercially available transportable fNIRS systems have a time resolution of 1-10 Hz, a depth sensitivity of about 1.5 cm, and a spatial resolution of about 1cm. The goal of this brief review is to report infants, children and adults fNIRS language studies. Since 1998, 60 studies have been published on cortical activation in the brain's classic language areas in children/adults as well as newborns using fNIRS instrumentations of different complexity. In addition, the basic principles of fNIRS including features, strengths, advantages, and limitations are summarized in terms that can be understood even by non specialists. Future prospects of fNIRS in the field of language processing imaging are highlighted. Copyright © 2011 Elsevier Inc. All rights reserved.

Glucose transporter expression in human skeletal muscle fibers

DEFF Research Database (Denmark)

Gaster, M; Handberg, A; Beck-Nielsen, H

2000-01-01

, but its expression is markedly reduced around birth and is further reduced to undetectable levels within the first year of life; 2) GLUT-3 protein expression appears at 18 wk of gestation and disappears after birth; and 3) GLUT-4 protein is diffusely expressed in muscle cells throughout gestation, whereas...... after birth, the characteristic subcellular localization is as seen in adult muscle fibers. Our results show that GLUT-1, GLUT-3, and GLUT-4 seem to be of importance during muscle fiber growth and development. GLUT-5 protein was undetectable in fetal and adult skeletal muscle fibers. In adult muscle...... amplification (TSA) technique to detect the localization of glucose transporter expression in human skeletal muscle. We found expression of GLUT-1, GLUT-3, and GLUT-4 in developing human muscle fibers showing a distinct expression pattern. 1) GLUT-1 is expressed in human skeletal muscle cells during gestation...

Ex-Vivo Tissues Engineering Modeling for Reconstructive Surgery Using Human Adult Adipose Stem Cells and Polymeric Nanostructured Matrix.

Science.gov (United States)

Morena, Francesco; Argentati, Chiara; Calzoni, Eleonora; Cordellini, Marino; Emiliani, Carla; D'Angelo, Francesco; Martino, Sabata

2016-03-31

The major challenge for stem cell translation regenerative medicine is the regeneration of damaged tissues by creating biological substitutes capable of recapitulating the missing function in the recipient host. Therefore, the current paradigm of tissue engineering strategies is the combination of a selected stem cell type, based on their capability to differentiate toward committed cell lineages, and a biomaterial, that, due to own characteristics (e.g., chemical, electric, mechanical property, nano-topography, and nanostructured molecular components), could serve as active scaffold to generate a bio-hybrid tissue/organ. Thus, effort has been made on the generation of in vitro tissue engineering modeling. Here, we present an in vitro model where human adipose stem cells isolated from lipoaspirate adipose tissue and breast adipose tissue, cultured on polymeric INTEGRA ® Meshed Bilayer Wound Matrix (selected based on conventional clinical applications) are evaluated for their potential application for reconstructive surgery toward bone and adipose tissue. We demonstrated that human adipose stem cells isolated from lipoaspirate and breast tissue have similar stemness properties and are suitable for tissue engineering applications. Finally, the overall results highlighted lipoaspirate adipose tissue as a good source for the generation of adult adipose stem cells.

Adult hippocampal neurogenesis and cognitive aging

Directory of Open Access Journals (Sweden)

Román Darío Moreno Fernández

2013-12-01

Full Text Available Aging is a normal developmental process associated with neurobiological changes leading to cognitive alterations with preserved, impaired, and enhanced functions. Evidence from animal and human studies is reviewed to explore the potential role of hippocampal plasticity on age-related cognitive changes with special attention to adult hippocampal neurogenesis. Results from lesion and stimulation strategies, as well as correlation data, support either a direct or modulatory role for adult newborn neurons in cognition at advanced ages. Further research on this topic may help to develop new treatments and to improve the quality of life of older people.

2014 Child and Adult Health Care Quality Measures

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U.S. Department of Health & Human Services — Performance rates on frequently reported health care quality measures in the CMS Medicaid/CHIP Child and Adult Core Sets, for FFY 2014 reporting. Dataset contains...

2016 Child and Adult Health Care Quality Measures

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U.S. Department of Health & Human Services — Performance rates on frequently reported health care quality measures in the CMS Medicaid/CHIP Child and Adult Core Sets, for FFY 2016 reporting. Source: Mathematica...

2015 Child and Adult Health Care Quality Measures

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U.S. Department of Health & Human Services — Performance rates on frequently reported health care quality measures in the CMS Medicaid/CHIP Child and Adult Core Sets, for FFY 2015 reporting. Source: Mathematica...

Per rectal endoscopic myotomy for the treatment of adult Hirschsprung's disease: First human case (with video).

Science.gov (United States)

Bapaye, Amol; Wagholikar, Gajanan; Jog, Sameer; Kothurkar, Aditi; Purandare, Shefali; Dubale, Nachiket; Pujari, Rajendra; Mahadik, Mahesh; Vyas, Viral; Bapaye, Jay

2016-09-01

Hirschsprung's disease (HD) is a congenital disorder characterized by the absence of intrinsic ganglion cells in submucosal and myenteric plexuses of the hindgut; and presents with constipation, intestinal obstruction and/or megacolon. HD commonly involves the rectosigmoid region (short segment HD), although shorter and longer variants of the disease are described. Standard treatment involves pull-through surgery for short segment HD or posterior anorectal myotomy in selected ultrashort segment candidates. Third space endoscopy has evolved during the past few years. Per oral endoscopic myotomy and per oral pyloromyotomy are described for treatment of achalasia cardia and refractory gastroparesis, respectively. Using the same philosophy of muscle/sphincter disruption for spastic bowel segments, per rectal endoscopic myotomy could be considered as a treatment option for short segment HD. A 24-year-old male patient presented with refractory constipation since childhood, and habituated to high-dose laxative combinations. Diagnosis was confirmed as adult short segment HD by barium enema, colonoscopic deep suction mucosal biopsies and anorectal manometry. Histopathology confirmed aganglionosis in the distal 15 cm. By implementing principles of third space endoscopy, per rectal endoscopic myotomy 20 cm in length was successfully carried out. At 24-week follow up, the patient reported significant relief of constipation and associated symptoms. Sigmoidoscopy, anorectal manometry and barium enema confirm improved rectal distensibility and reduced rectal pressures. The present case report describes the first human experience of per rectal endoscopic myotomy for successful treatment of adult short segment HD. © 2016 Japan Gastroenterological Endoscopy Society.

Global perpectives on adult education and learning policy

DEFF Research Database (Denmark)

on citizenship and democracy. It highlights several significant shifts: increased awareness of the role of adult education/lifelong learning in enhancing economic growth and social cohesion and mobility, challenging economic and social exclusion and inequality, and developing human and social capital; increased......Most observers regard both adult and higher education as key for citizenship and democracy yet the worldwide contexts, appearance and expression of adult education and lifelong learning have changed significantly during the past 20 years. Focusing on ten countries (Scotland, Czech Republic, USA......, Brazil, Mexico, Botswana, Ghana, Palestine, South Korea and India) and five international organisations, this book explores recent changes in their overall contexts and policies about adult education, how such policies intersect with developments in higher education and how they may contribute to debates...

Voltage-gated ion channels in the axon initial segment of human cortical pyramidal cells and their relationship with chandelier cells.

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Inda, Maria Carmen; DeFelipe, Javier; Muñoz, Alberto

2006-02-21

The axon initial segment (AIS) of pyramidal cells is a critical region for the generation of action potentials and for the control of pyramidal cell activity. Here we show that Na+ and K+ voltage-gated channels, together with other molecules involved in the localization of ion channels, are distributed asymmetrically in the AIS of pyramidal cells situated in the human temporal neocortex. There is a high density of Na+ channels distributed along the length of the AIS together with the associated proteins spectrin betaIV and ankyrin G. In contrast, Kv1.2 channels are associated with the adhesion molecule Caspr2, and they are mostly localized to the distal region of the AIS. In general, the distal region of the AIS is targeted by the GABAergic axon terminals of chandelier cells, whereas the proximal region is innervated, mostly by other types of GABAergic interneurons. We suggest that this molecular segregation and the consequent regional specialization of the GABAergic input to the AIS of pyramidal cells may have important functional implications for the control of pyramidal cell activity.

Analysis of gene expression in fetal and adult cells infected with rubella virus

International Nuclear Information System (INIS)

Adamo, Maria Pilar; Zapata, Marta; Frey, Teryl K.

2008-01-01

Congenital infection with rubella virus (RUB) leads to persistent infection and congenital defects and we showed previously that primary human fetal fibroblasts did not undergo apoptosis when infected with RUB, which could promote fetal virus persistence [Adamo, P., Asis, L., Silveyra, P., Cuffini, C., Pedranti, M., Zapata, M., 2004. Rubella virus does not induce apoptosis in primary human embryo fibroblasts cultures: a possible way of viral persistence in congenital infection. Viral Immunol. 17, 87-100]. To extend this observation, gene chip analysis was performed on a line of primary human fetal fibroblasts (10 weeks gestation) and a line of human adult lung fibroblasts (which underwent apoptosis in response to RUB infection) to compare gene expression in infected and uninfected cells. A total of 632 and 516 genes were upregulated or downregulated in the infected fetal and adult cells respectively in comparison to uninfected cells, however only 52 genes were regulated in both cell types. Although the regulated genes were different, across functional gene categories the patterns of gene regulation were similar. In general, regulation of pro- and anti-apoptotic genes following infection appeared to favor apoptosis in the adult cells and lack of apoptosis in the fetal cells, however there was a greater relative expression of anti-apoptotic genes and reduced expression of pro-apoptotic genes in uninfected fetal cells versus uninfected adult cells and thus the lack of apoptosis in fetal cells following RUB infection was also due to the prevailing background of gene expression that is antagonistic to apoptosis. In support of this hypothesis, it was found that of a battery of five chemicals known to induce apoptosis, two induced apoptosis in the adult cells, but not in fetal cells, and two induced apoptosis more rapidly in the adult cells than in fetal cells (the fifth did not induce apoptosis in either). A robust interferon-stimulated gene response was induced

Reducing Student Bias against Older Adults through the Use of Literature

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Tice, Carolyn J.; Harnek Hall, Diane M.; Miller, Shari E.

2010-01-01

Human services educators must address the issue of students' bias toward older adults to encourage interest and meet the growing need for professionals in the field. The use of literature can challenge students' preconceptions of older adults while innovative teaching methods can guide their development of more tolerant views and introduce them to…

Quantitative analysis of DNA methylation at all human imprinted regions reveals preservation of epigenetic stability in adult somatic tissue

Directory of Open Access Journals (Sweden)

Woodfine Kathryn

2011-01-01

Full Text Available Abstract Background Genes subject to genomic imprinting are mono-allelically expressed in a parent-of-origin dependent manner. Each imprinted locus has at least one differentially methylated region (DMR which has allele specific DNA methylation and contributes to imprinted gene expression. Once DMRs are established, they are potentially able to withstand normal genome reprogramming events that occur during cell differentiation and germ-line DMRs are stably maintained throughout development. These DMRs, in addition to being either maternally or paternally methylated, have differences in whether methylation was acquired in the germ-line or post fertilization and are present in a variety of genomic locations with different Cytosine-phosphate guanine (CpG densities and CTCF binding capacities. We therefore examined the stability of maintenance of DNA methylation imprints and determined the normal baseline DNA methylation levels in several adult tissues for all imprinted genes. In order to do this, we first developed and validated 50 highly specific, quantitative DNA methylation pyrosequencing assays for the known DMRs associated with human imprinted genes. Results Remarkable stability of the DNA methylation imprint was observed in all germ-line DMRs and paternally methylated somatic DMRs (which maintained average methylation levels of between 35% - 65% in all somatic tissues, independent of gene expression. Maternally methylated somatic DMRs were found to have more variation with tissue specific methylation patterns. Most DMRs, however, showed some intra-individual variability for DNA methylation levels in peripheral blood, suggesting that more than one DMR needs to be examined in order to get an overall impression of the epigenetic stability in a tissue. The plasticity of DNA methylation at imprinted genes was examined in a panel of normal and cancer cell lines. All cell lines showed changes in DNA methylation, especially at the paternal germ

Human evolution and osteoporosis-related spinal fractures.

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Meghan M Cotter

Full Text Available The field of evolutionary medicine examines the possibility that some diseases are the result of trade-offs made in human evolution. Spinal fractures are the most common osteoporosis-related fracture in humans, but are not observed in apes, even in cases of severe osteopenia. In humans, the development of osteoporosis is influenced by peak bone mass and strength in early adulthood as well as age-related bone loss. Here, we examine the structural differences in the vertebral bodies (the portion of the vertebra most commonly involved in osteoporosis-related fractures between humans and apes before age-related bone loss occurs. Vertebrae from young adult humans and chimpanzees, gorillas, orangutans, and gibbons (T8 vertebrae, n = 8-14 per species, male and female, humans: 20-40 years of age were examined to determine bone strength (using finite element models, bone morphology (external shape, and trabecular microarchitecture (micro-computed tomography. The vertebrae of young adult humans are not as strong as those from apes after accounting for body mass (p<0.01. Human vertebrae are larger in size (volume, cross-sectional area, height than in apes with a similar body mass. Young adult human vertebrae have significantly lower trabecular bone volume fraction (0.26±0.04 in humans and 0.37±0.07 in apes, mean ± SD, p<0.01 and thinner vertebral shells than apes (after accounting for body mass, p<0.01. Since human vertebrae are more porous and weaker than those in apes in young adulthood (after accounting for bone mass, even modest amounts of age-related bone loss may lead to vertebral fracture in humans, while in apes, larger amounts of bone loss would be required before a vertebral fracture becomes likely. We present arguments that differences in vertebral bone size and shape associated with reduced bone strength in humans is linked to evolutionary adaptations associated with bipedalism.

TP53 mutation and human papilloma virus status of oral squamous cell carcinomas in young adult patients.

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Braakhuis, B J M; Rietbergen, M M; Buijze, M; Snijders, P J F; Bloemena, E; Brakenhoff, R H; Leemans, C R

2014-09-01

Little is known about the molecular carcinogenesis of oral squamous cell carcinoma (OSCC) in young adult patients. The aim of this study was to investigate the detailed TP53 mutation and human papilloma virus (HPV) status of OSCC in patients, younger than 45 years. TP53 mutations were determined with direct sequencing on paraffin-embedded carcinoma tissue from 31 young patients and compared with two older age OSCC reference groups: one from the same institute (N = 87) and an independent one (N = 675). Biologically active tumour HPV was detected by p16-immunohistochemistry followed by a HPV-DNA GP5 + /6 + -PCR. HPV16 was present in one OSCC (3%). TP53 mutations were found in 14 (45%) OSCC: five were missense and nine resulted in a truncated protein. Six of these latter were insertions or deletions of one or more nucleotides leading to frameshift, one was at a splice site and two resulted in a stop codon. The percentage of truncating mutations (64% of all mutations) was higher than that observed in the institute's reference group (44%, P = 0.23) and in the independent reference group (24%, P = 0.002). This study shows that TP53 mutations are common in OSCC of young adult patients; infection with biologically active HPV is rare. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Gene expression profiling and secretome analysis differentiate adult-derived human liver stem/progenitor cells and human hepatic stellate cells.

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Silvia Berardis

Full Text Available Adult-derived human liver stem/progenitor cells (ADHLSC are obtained after primary culture of the liver parenchymal fraction. The cells are of fibroblastic morphology and exhibit a hepato-mesenchymal phenotype. Hepatic stellate cells (HSC derived from the liver non-parenchymal fraction, present a comparable morphology as ADHLSC. Because both ADHLSC and HSC are described as liver stem/progenitor cells, we strived to extensively compare both cell populations at different levels and to propose tools demonstrating their singularity. ADHLSC and HSC were isolated from the liver of four different donors, expanded in vitro and followed from passage 5 until passage 11. Cell characterization was performed using immunocytochemistry, western blotting, flow cytometry, and gene microarray analyses. The secretion profile of the cells was evaluated using Elisa and multiplex Luminex assays. Both cell types expressed α-smooth muscle actin, vimentin, fibronectin, CD73 and CD90 in accordance with their mesenchymal origin. Microarray analysis revealed significant differences in gene expression profiles. HSC present high expression levels of neuronal markers as well as cytokeratins. Such differences were confirmed using immunocytochemistry and western blotting assays. Furthermore, both cell types displayed distinct secretion profiles as ADHLSC highly secreted cytokines of therapeutic and immuno-modulatory importance, like HGF, interferon-γ and IL-10. Our study demonstrates that ADHLSC and HSC are distinct liver fibroblastic cell populations exhibiting significant different expression and secretion profiles.

Molecular identification of Giardia lamblia isolates from adult human ...

African Journals Online (AJOL)

ARL

2013-02-27

Feb 27, 2013 ... Giardia lamblia is a flagellated protozoa that infects the intestinal tract of a wide range of mammalian hosts, including both wild and domestic animals as well as humans. Two genotypes A and B are commonly reported among humans. The purpose of this study was to investigate the genotypes of G.

Human adenovirus-36 and childhood obesity.

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Atkinson, Richard L

2011-09-01

There is increasing evidence that obesity in humans is associated with infection with human adenovirus-36 (Adv36). Infection of experimental animals with Adv36 demonstrates that this virus causes obesity. Human studies have shown a prevalence of Adv36 infection of 30% or greater in obese adult humans, but a correlation with obesity has not always been demonstrated. In contrast, three published studies and one presented study with a total of 559 children all show that there is an increase in prevalence of Adv36 infection in obese children (28%) compared to non-obese children (10%). The explanation for the apparently more robust correlation of Adv36 infection with obesity in children vs. adults is not clear. The data in animals and people suggests that Adv36 has contributed to the worldwide increase in childhood obesity. More research is needed to identify prevalences and consequences of Adv36 infection in people of all age groups and geographic locations.

Comparison of Kaposi Sarcoma Risk in Human Immunodeficiency Virus-Positive Adults Across 5 Continents: A Multiregional Multicohort Study.

Science.gov (United States)

2017-10-15

We compared Kaposi sarcoma (KS) risk in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America. We included cohort data of human immunodeficiency virus (HIV)-positive adults who started ART after 1995 within the framework of 2 large collaborations of observational HIV cohorts. We present incidence rates and adjusted hazard ratios (aHRs). We included 208140 patients from 57 countries. Over a period of 1066572 person-years, 2046 KS cases were diagnosed. KS incidence rates per 100000 person-years were 52 in the Asia-Pacific and ranged between 180 and 280 in the other regions. KS risk was 5 times higher in South African women (aHR, 4.56; 95% confidence intervals [CI], 2.73-7.62) than in their European counterparts, and 2 times higher in South African men (2.21; 1.34-3.63). In Europe, Latin, and North America KS risk was 6 times higher in men who have sex with men (aHR, 5.95; 95% CI, 5.09-6.96) than in women. Comparing patients with current CD4 cell counts ≥700 cells/µL with those whose counts were <50 cells/µL, the KS risk was halved in South Africa (aHR, 0.53; 95% CI, .17-1.63) but reduced by ≥95% in other regions. Despite important ART-related declines in KS incidence, men and women in South Africa and men who have sex with men remain at increased KS risk, likely due to high human herpesvirus 8 coinfection rates. Early ART initiation and maintenance of high CD4 cell counts are essential to further reducing KS incidence worldwide, but additional measures might be needed, especially in Southern Africa. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com

Validation of case-finding algorithms derived from administrative data for identifying adults living with human immunodeficiency virus infection.

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Tony Antoniou

Full Text Available OBJECTIVE: We sought to validate a case-finding algorithm for human immunodeficiency virus (HIV infection using administrative health databases in Ontario, Canada. METHODS: We constructed 48 case-finding algorithms using combinations of physician billing claims, hospital and emergency room separations and prescription drug claims. We determined the test characteristics of each algorithm over various time frames for identifying HIV infection, using data abstracted from the charts of 2,040 randomly selected patients receiving care at two medical practices in Toronto, Ontario as the reference standard. RESULTS: With the exception of algorithms using only a single physician claim, the specificity of all algorithms exceeded 99%. An algorithm consisting of three physician claims over a three year period had a sensitivity and specificity of 96.2% (95% CI 95.2%-97.9% and 99.6% (95% CI 99.1%-99.8%, respectively. Application of the algorithm to the province of Ontario identified 12,179 HIV-infected patients in care for the period spanning April 1, 2007 to March 31, 2009. CONCLUSIONS: Case-finding algorithms generated from administrative data can accurately identify adults living with HIV. A relatively simple "3 claims in 3 years" definition can be used for assembling a population-based cohort and facilitating future research examining trends in health service use and outcomes among HIV-infected adults in Ontario.

99mTc-ECD brain perfusion SPET: variability, asymmetry and effects of age and gender in healthy adults

International Nuclear Information System (INIS)

Van Laere, K.; Versijpt, J.; Goethals, I.; Dierckx, R.; Audenaert, K.; Koole, M.; Achten, E.

2001-01-01

Reliable and high-resolution reference data for regional cerebral blood flow measured with single-photon emission tomography (SPET) are necessary for optimal clinical and research use. Therefore, a large dataset of normal technetium-99m labelled ethylene cysteine dimer (ECD) perfusion SPET in carefully screened healthy volunteers with an age range spanning six decades was created, with correction for non-uniform attenuation and scatter and based on an anatomically standardised analysis. Eighty-nine healthy volunteers, stratified for gender (46 females, 43 males; age 20-81 years), were included. Twelve volunteers underwent repeated 99m Tc-ECD SPET after 2.5±2.3 weeks. An automated whole-brain volume of interest analysis with MANOVA as well as voxelwise analysis using SPM99 was conducted. Average intersubject variability was 4.8% while intrasubject reproducibility was 3.0%. An age-related decline in tracer uptake was found in the anterior cingulate gyrus, bilateral basal ganglia, left prefrontal, left lateral frontal and left superior temporal and insular cortex (all P=0.001-0.02). There was an overall increase in right/left asymmetry with age, which was most pronounced in the frontal and temporal neocortex. The most significant correlations between AI and age decade were found in the prefrontal (R=0.35, P=0.001) and superior temporal neocortex (R=0.43, P 99m Tc-ECD perfusion SPET under a wide variety of clinical circumstances in relation to normal variations and highlights the importance of both age- and gender-specific normal datasets for optimal analysis sensitivity. (orig.)

Developmental reversals in recognition memory in children and adults.

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Gross, Julien; Gardiner, Beatrix; Hayne, Harlene

2016-01-01

Older members of a given species typically exhibit superior learning and memory abilities relative to younger members, however, the developmental difference does not always occur in this younger-to-older direction. Developmental reversals are thought to reflect adaptive responses to the unique challenges imposed by the infant's niche. In humans, identification of developmental reversals has largely been precluded because infants, children, and adults are rarely tested using the same experimental procedures. Here, we adapted the visual recognition memory task and tested 3-year-olds and adults using one set of child-oriented stimuli and one set of adult-orientated stimuli. When tested immediately, children and adults exhibited recognition memory for both stimuli. When tested after a 1-week delay, children exhibited recognition memory for the child-oriented stimuli, but not for the adult-oriented stimuli and adults exhibited recognition memory for the adult-oriented stimuli, but not for the child-oriented stimuli. These data have important implications for current theories of memory development. © 2015 Wiley Periodicals, Inc.

Zebrafish adult-derived hypothalamic neurospheres generate gonadotropin-releasing hormone (GnRH neurons

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Christian Cortés-Campos

2015-09-01

Full Text Available Gonadotropin-releasing hormone (GnRH is a hypothalamic decapeptide essential for fertility in vertebrates. Human male patients lacking GnRH and treated with hormone therapy can remain fertile after cessation of treatment suggesting that new GnRH neurons can be generated during adult life. We used zebrafish to investigate the neurogenic potential of the adult hypothalamus. Previously we have characterized the development of GnRH cells in the zebrafish linking genetic pathways to the differentiation of neuromodulatory and endocrine GnRH cells in specific regions of the brain. Here, we developed a new method to obtain neural progenitors from the adult hypothalamus in vitro. Using this system, we show that neurospheres derived from the adult hypothalamus can be maintained in culture and subsequently differentiate glia and neurons. Importantly, the adult derived progenitors differentiate into neurons containing GnRH and the number of cells is increased through exposure to either testosterone or GnRH, hormones used in therapeutic treatment in humans. Finally, we show in vivo that a neurogenic niche in the hypothalamus contains GnRH positive neurons. Thus, we demonstrated for the first time that neurospheres can be derived from the hypothalamus of the adult zebrafish and that these neural progenitors are capable of producing GnRH containing neurons.

Sensory maps in the claustrum of the cat.

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Olson, C R; Graybiel, A M

1980-12-04

The claustrum is a telencephalic cell group (Fig. 1A, B) possessing widespread reciprocal connections with the neocortex. In this regard, it bears a unique and striking resemblance to the thalamus. We have now examined the anatomical ordering of pathways linking the claustrum with sensory areas of the cat neocortex and, in parallel electrophysiological experiments, have studied the functional organization of claustral sensory zones so identified. Our findings indicate that there are discrete visual and somatosensory subdivisions in the claustrum interconnected with the corresponding primary sensory areas of the neocortex and that the respective zones contain orderly retinotopic and somatotopic maps. A third claustral region receiving fibre projections from the auditory cortex in or near area Ep was found to contain neurones responsive to auditory stimulation. We conclude that loops connecting sensory areas of the neocortex with satellite zones in the claustrum contribute to the early processing of exteroceptive information by the forebrain.

Higher-Order Synaptic Interactions Coordinate Dynamics in Recurrent Networks.

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Brendan Chambers

2016-08-01

Full Text Available Linking synaptic connectivity to dynamics is key to understanding information processing in neocortex. Circuit dynamics emerge from complex interactions of interconnected neurons, necessitating that links between connectivity and dynamics be evaluated at the network level. Here we map propagating activity in large neuronal ensembles from mouse neocortex and compare it to a recurrent network model, where connectivity can be precisely measured and manipulated. We find that a dynamical feature dominates statistical descriptions of propagating activity for both neocortex and the model: convergent clusters comprised of fan-in triangle motifs, where two input neurons are themselves connected. Fan-in triangles coordinate the timing of presynaptic inputs during ongoing activity to effectively generate postsynaptic spiking. As a result, paradoxically, fan-in triangles dominate the statistics of spike propagation even in randomly connected recurrent networks. Interplay between higher-order synaptic connectivity and the integrative properties of neurons constrains the structure of network dynamics and shapes the routing of information in neocortex.

High-Frequency Network Oscillations in Cerebellar Cortex

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Middleton, Steven J.; Racca, Claudia; Cunningham, Mark O.; Traub, Roger D.; Monyer, Hannah; Knöpfel, Thomas; Schofield, Ian S.; Jenkins, Alistair; Whittington, Miles A.

2016-01-01

SUMMARY Both cerebellum and neocortex receive input from the somatosensory system. Interaction between these regions has been proposed to underpin the correct selection and execution of motor commands, but it is not clear how such interactions occur. In neocortex, inputs give rise to population rhythms, providing a spatiotemporal coding strategy for inputs and consequent outputs. Here, we show that similar patterns of rhythm generation occur in cerebellum during nicotinic receptor subtype activation. Both gamma oscillations (30–80 Hz) and very fast oscillations (VFOs, 80–160 Hz) were generated by intrinsic cerebellar cortical circuitry in the absence of functional glutamatergic connections. As in neocortex, gamma rhythms were dependent on GABAA receptor-mediated inhibition, whereas VFOs required only nonsynaptically connected intercellular networks. The ability of cerebellar cortex to generate population rhythms within the same frequency bands as neocortex suggests that they act as a common spatiotemporal code within which corticocerebellar dialog may occur. PMID:18549787

Fetal hyperglycemia changes human preadipocyte function in adult life

DEFF Research Database (Denmark)

Hansen, Ninna Schiøler; Strasko, Klaudia Stanislawa; Hjort, Line

2017-01-01

Context: Offspring of women with gestational diabetes (O-GDM) or type 1 diabetes mellitus (O-T1DM) have been exposed to hyperglycemia in utero and have an increased risk of developing metabolic disease in adulthood. Design: In total, we recruited 206 adult offspring comprising the two fetal...... acid supply. Conclusions: Taken together, these findings show that intrinsic epigenetic and functional changes exist in preadipocyte cultures from individuals exposed to fetal hyperglycemia who are at increased risk of developing metabolic disease....

Changes in radiation dose with variations in human anatomy: moderately and severely obese adults.

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Clark, Landon D; Stabin, Michael G; Fernald, Michael J; Brill, Aaron B

2010-06-01

The phantoms used in standardized dose assessment are based on a median (i.e., 50th percentile) individual of a large population, for example, adult males or females or children of a particular age. Here we describe phantoms that model instead the influence of obesity on specific absorbed fractions (SAFs) and dose factors in adults. The literature was reviewed to evaluate how individual organ sizes change with variations in body weight in mildly and severely obese adult men and women. On the basis of the literature evaluation, changes were made to our deformable reference adult male and female total-body models. Monte Carlo simulations of radiation transport were performed. SAFs for photons were generated for mildly and severely obese adults, and comparisons were made to the reference (50th) percentile SAF values. SAFs studied between the obese phantoms and the 50th percentile reference phantoms were not significantly different from the reference 50th percentile individual, with the exception of intestines irradiating some abdominal organs, because of an increase in separation between folds caused by an increase in mesenteric adipose deposits. Some low-energy values for certain organ pairs were different, possibly due only to the statistical variability of the data at these low energies. The effect of obesity on dose calculations for internal emitters is minor and may be neglected in the routine use of standardized dose estimates.

Growth of the human lens in the Indian adult population: Preliminary observations

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Ashik Mohamed

2012-01-01

Full Text Available Context: The eye lens grows throughout life by the addition of new cells inside the surrounding capsule. How this growth affects the properties of the lens is essential for understanding disorders such as cataract and presbyopia. Aims: To examine growth of the human lens in the Indian population and compare this with the growth in Western populations by measuring in vitro dimensions together with wet and dry weights. Settings and Design: The study was conducted at the research wing of a tertiary eye care center in South India and the study design was prospective. Materials and Methods: Lenses were removed from eye bank eyes and their dimensions measured with a digital caliper. They were then carefully blotted dry and weighed before being placed in 5% buffered formalin. After 1 week fixation, the lenses were dried at 80 °C until constant weight was achieved. The constant weight was noted as the dry weight of the lens. Statistical Analysis Used: Lens parameters were analyzed as a function of age using linear and logarithmic regression methods. Results: Data were obtained for 251 lenses, aged 16-93 years, within a median postmortem time of 22 h. Both wet and dry weights increased linearly at 1.24 and 0.44 mg/year, respectively, throughout adult life. The dimensions also increased continuously throughout this time. Conclusions: Over the age range examined, lens growth in the Indian population is very similar to that in Western populations.

Bare lymphocyte syndrome: imaging findings in an adult

International Nuclear Information System (INIS)

Bernaerts, A.; Vandevenne, J.E.; De Schepper, A.M.; Lambert, J.; De Clerck, L.S.

2001-01-01

Bare lymphocyte syndrome (BLS) is a rare primary immune disorder characterized by defective expression of human leukocyte antigen (HLA) on lymphocytes, often resulting in extensive and recurrent multi-organ infections. We describe a previously undiagnosed case of an adult woman who presented with radiological findings of severe bronchiectases, near-total granulomatous destruction of facial bones, and osteomyelitis. Diagnosis of BLS should be considered when evaluating children with unexplained bronchiectases or adults with long history of chronic multi-organ infections. (orig.)

Bounded Rationality, Emotions and Older Adult Decision Making: Not so Fast and yet so Frugal

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Hanoch, Yaniv; Wood, Stacey; Rice, Thomas

2007-01-01

Herbert Simon's work on bounded rationality has had little impact on researchers studying older adults' decision making. This omission is surprising, as human constraints on computation and memory are exacerbated in older adults. The study of older adults' decision-making processes could benefit from employing a bounded rationality perspective,…

Structural and functional analyses of human cerebral cortex using a surface-based atlas

Science.gov (United States)

Van Essen, D. C.; Drury, H. A.

1997-01-01

We have analyzed the geometry, geography, and functional organization of human cerebral cortex using surface reconstructions and cortical flat maps of the left and right hemispheres generated from a digital atlas (the Visible Man). The total surface area of the reconstructed Visible Man neocortex is 1570 cm2 (both hemispheres), approximately 70% of which is buried in sulci. By linking the Visible Man cerebrum to the Talairach stereotaxic coordinate space, the locations of activation foci reported in neuroimaging studies can be readily visualized in relation to the cortical surface. The associated spatial uncertainty was empirically shown to have a radius in three dimensions of approximately 10 mm. Application of this approach to studies of visual cortex reveals the overall patterns of activation associated with different aspects of visual function and the relationship of these patterns to topographically organized visual areas. Our analysis supports a distinction between an anterior region in ventral occipito-temporal cortex that is selectively involved in form processing and a more posterior region (in or near areas VP and V4v) involved in both form and color processing. Foci associated with motion processing are mainly concentrated in a region along the occipito-temporal junction, the ventral portion of which overlaps with foci also implicated in form processing. Comparisons between flat maps of human and macaque monkey cerebral cortex indicate significant differences as well as many similarities in the relative sizes and positions of cortical regions known or suspected to be homologous in the two species.

Human Albumin Use in Adults in U.S. Academic Medical Centers.

Science.gov (United States)

Suarez, Jose I; Martin, Renee H; Hohmann, Samuel F; Calvillo, Eusebia; Bershad, Eric M; Venkatasubba Rao, Chethan P; Georgiadis, Alexandros; Flower, Oliver; Zygun, David; Finfer, Simon

2017-01-01

To determine rates and predictors of albumin administration, and estimated costs in hospitalized adults in the United States. Cohort study of adult patients from the University HealthSystem Consortium database from 2009 to 2013. One hundred twenty academic medical centers and 299 affiliated hospitals. A total of 12,366,264 hospitalization records. Analysis of rates and predictors of albumin administration, and estimated costs. Overall the proportion of admissions during which albumin was administered increased from 6.2% in 2009 to 7.5% in 2013; absolute difference 1.3% (95% CI, 1.30-1.40%; p Albumin use varied geographically being lowest with no increase in hospitals in the North Eastern United States (4.9% in 2009 and 5.3% in 2013) and was more common in bigger (> 750 beds; 5.2% in 2009 and 7.3% in 2013) compared to smaller hospitals (albumin use were appropriate indication for albumin use (odds ratio, 65.220; 95% CI, 62.459-68.103); surgical admission (odds ratio, 7.942; 95% CI, 7.889-7.995); and high severity of illness (odds ratio, 8.933; 95% CI, 8.825-9.042). Total estimated albumin cost significantly increased from $325 million in 2009 to $468 million in 2013; (absolute increase of $233 million), p value less than 0.0001. The proportion of hospitalized adults in the United States receiving albumin has increased, with marked, and currently unexplained, geographic variability and variability by hospital size.

Walking Stability during Cell Phone Use in Healthy Adults

OpenAIRE

Kao, Pei-Chun; Higginson, Christopher I.; Seymour, Kelly; Kamerdze, Morgan; Higginson, Jill S.

2015-01-01

The number of falls and/or accidental injuries associated with cellular phone use during walking is growing rapidly. Understanding the effects of concurrent cell phone use on human gait may help develop safety guidelines for pedestrians. It was shown previously that older adults had more pronounced dual-task interferences than younger adults when concurrent cognitive task required visual information processing. Thus, cell phone use might have greater impact on walking stability in older than ...