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Sample records for human adults showed

  1. 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.

  2. Human-directed social behaviour in dogs shows significant heritability.

    Science.gov (United States)

    Persson, M E; Roth, L S V; Johnsson, M; Wright, D; Jensen, P

    2015-04-01

    Through domestication and co-evolution with humans, dogs have developed abilities to attract human attention, e.g. in a manner of seeking assistance when faced with a problem solving task. The aims of this study were to investigate within breed variation in human-directed contact seeking in dogs and to estimate its genetic basis. To do this, 498 research beagles, bred and kept under standardized conditions, were tested in an unsolvable problem task. Contact seeking behaviours recorded included both eye contact and physical interactions. Behavioural data was summarized through a principal component analysis, resulting in four components: test interactions, social interactions, eye contact and physical contact. Females scored significantly higher on social interactions and physical contact and age had an effect on eye contact scores. Narrow sense heritabilities (h(2) ) of the two largest components were estimated at 0.32 and 0.23 but were not significant for the last two components. These results show that within the studied dog population, behavioural variation in human-directed social behaviours was sex dependent and that the utilization of eye contact seeking increased with age and experience. Hence, heritability estimates indicate a significant genetic contribution to the variation found in human-directed social interactions, suggesting that social skills in dogs have a genetic basis, but can also be shaped and enhanced through individual experiences. This research gives the opportunity to further investigate the genetics behind dogs' social skills, which could also play a significant part into research on human social disorders such as autism. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  3. Free-ranging dogs show age related plasticity in their ability to follow human pointing.

    Science.gov (United States)

    Bhattacharjee, Debottam; N, Nikhil Dev; Gupta, Shreya; Sau, Shubhra; Sarkar, Rohan; Biswas, Arpita; Banerjee, Arunita; Babu, Daisy; Mehta, Diksha; Bhadra, Anindita

    2017-01-01

    Differences in pet dogs' and captive wolves' ability to follow human communicative intents have led to the proposition of several hypotheses regarding the possession and development of social cognitive skills in dogs. It is possible that the social cognitive abilities of pet dogs are induced by indirect conditioning through living with humans, and studying free-ranging dogs can provide deeper insights into differentiating between innate abilities and conditioning in dogs. Free-ranging dogs are mostly scavengers, indirectly depending on humans for their sustenance. Humans can act both as food providers and as threats to these dogs, and thus understanding human gestures can be a survival need for the free-ranging dogs. We tested the responsiveness of such dogs in urban areas toward simple human pointing cues using dynamic proximal points. Our experiment showed that pups readily follow proximal pointing and exhibit weaker avoidance to humans, but stop doing so at the later stages of development. While juveniles showed frequent and prolonged gaze alternations, only adults adjusted their behaviour based on the reliability of the human experimenter after being rewarded. Thus free-ranging dogs show a tendency to respond to human pointing gestures, with a certain level of behavioural plasticity that allows learning from ontogenic experience.

  4. Dogs do not show pro-social preferences towards humans.

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    Mylène Quervel-Chaumette

    2016-10-01

    Full Text Available Pro-social behaviors are defined as voluntary actions that benefit others. Comparative studies have mostly focused on investigating the presence of pro-sociality across species in an intraspecific context. Taken together, results on both primates and non-primate species indicate that reliance on cooperation may be at work in the selection and maintenance of pro-social sentiments. Dogs appear to be the ideal model when investigating a species’ propensity for pro-sociality in an interspecific context since it has been suggested that as a consequence of domestication, they evolved an underlying temperament encouraging greater propensity to cooperate with human partners. In a recent study, using a food delivery paradigm, dogs were shown to preferentially express pro-social choices towards familiar compared to unfamiliar conspecifics. Using the same set-up and methods in the current study, we investigated dogs’ pro-social preferences towards familiar and unfamiliar human partners. We found that dogs’ pro-social tendencies did not extend to humans and the identity of the human partners did not influence the rate of food delivery. Interestingly, dogs tested with their human partners spent more time gazing at humans, and did so for longer after food consumption had ended than dogs tested with conspecific partners in the initial study. To allow comparability between results from dogs tested with a conspecific and a human partner, the latter were asked not to communicate with dogs in any way. However, this lack of communication from the human may have been aversive to dogs, leading them to cease performing the task earlier compared to the dogs paired with familiar conspecifics in the prior study. This is in line with previous findings suggesting that human communication in such contexts highly affects dogs’ responses. Consequently, we encourage further studies to examine dogs’ pro-social behavior towards humans taking into consideration their

  5. "Scientific peep show": the human body in contemporary science museums.

    Science.gov (United States)

    Canadelli, Elena

    2011-01-01

    The essay focuses on the discourse about the human body developed by contemporary science museums with educational and instructive purposes directed at the general public. These museums aim mostly at mediating concepts such as health and prevention. The current scenario is linked with two examples of past museums: the popular anatomical museums which emerged during the 19th century and the health museums thrived between 1910 and 1940. On the museological path about the human body self-care we went from the emotionally involving anatomical Venuses to the inexpressive Transparent Man, from anatomical specimens of ill organs and deformed subjects to the mechanical and electronic models of the healthy body. Today the body is made transparent by the new medical diagnostics and by the latest discoveries of endoscopy. The way museums and science centers presently display the human body involves computers, 3D animation, digital technologies, hands-on models of large size human parts.

  6. Human placental immunoglobulins show unique re-association ...

    African Journals Online (AJOL)

    Objective: To study re-association pattern of human placental eluate immunoglobulins with acid treated isologous and third party trophoblast derived placental microvesicles. Design: Laboratory based experimentation. Setting: Biological Sciences Department and Discipline for Reproductive Medicine University of ...

  7. Immature rats show ovulatory defects similar to those in adult rats lacking prostaglandin and progesterone actions

    Directory of Open Access Journals (Sweden)

    Sanchez-Criado Jose E

    2004-09-01

    Full Text Available Abstract Gonadotropin-primed immature rats (GPIR constitute a widely used model for the study of ovulation. Although the equivalence between the ovulatory process in immature and adult rats is generally assumed, the morphological and functional characteristics of ovulation in immature rats have been scarcely considered. We describe herein the morphological aspects of the ovulatory process in GPIR and their response to classical ovulation inhibitors, such as the inhibitor of prostaglandin (PG synthesis indomethacin (INDO and a progesterone (P receptor (PR antagonist (RU486. Immature Wistar rats were primed with equine chorionic gonadotropin (eCG at 21, 23 or 25 days of age, injected with human chorionic gonadotropin (hCG 48 h later, and sacrificed 16 h after hCG treatment, to assess follicle rupture and ovulation. Surprisingly, GPIR showed age-related ovulatory defects close similar to those in adult rats lacking P and PG actions. Rats primed with eCG at 21 or 23 days of age showed abnormally ruptured corpora lutea in which the cumulus-oocyte complex (COC was trapped or had been released to the ovarian interstitum, invading the ovarian stroma and blood and lymphatic vessels. Supplementation of immature rats with exogenous P and/or PG of the E series did not significantly inhibit abnormal follicle rupture. Otherwise, ovulatory defects were practically absent in rats primed with eCG at 25 days of age. GPIR treated with INDO showed the same ovulatory alterations than vehicle-treated ones, although affecting to a higher proportion of follicles. Blocking P actions with RU486 increased the number of COC trapped inside corpora lutea and decreased ovulation. The presence of ovulatory defects in GPIR, suggests that the capacity of the immature ovary to undergo the coordinate changes leading to effective ovulation is not fully established in Wistar rats primed with eCG before 25 days of age.

  8. Capuchin monkeys do not show human-like pricing effects

    Science.gov (United States)

    Catapano, Rhia; Buttrick, Nicholas; Widness, Jane; Goldstein, Robin; Santos, Laurie R.

    2014-01-01

    Recent work in judgment and decision-making has shown that a good's price can have irrational effects on people's preferences. People tend to prefer goods that cost more money and assume that such expensive goods will be more effective, even in cases where the price of the good is itself arbitrary. Although much work has documented the existence of these pricing effects, unfortunately little work has addressed where these price effects come from in the first place. Here we use a comparative approach to distinguish between different accounts of this bias and to explore the origins of these effects. Specifically, we test whether brown capuchin monkeys (Cebus apella) are also susceptible to pricing effects within the context of an experimentally trained token economy. Using a capuchin population previously trained in a token market, we explored whether monkeys used price as an indicator of value across four experiments. Although monkeys demonstrated an understanding of which goods had which prices (consistently shifting preferences to cheaper goods when prices were increased), we observed no evidence that such price information affected their valuation of different kinds of goods. These results suggest that human pricing effects may involve more sophisticated human-unique cognitive capacities, such as an understanding of market forces and signaling. PMID:25520677

  9. Capuchin monkeys do not show human-like pricing effects

    Directory of Open Access Journals (Sweden)

    Rhia eCatapano

    2014-12-01

    Full Text Available Recent work in judgment and decision-making has shown that a good’s price can have irrational effects on people’s preferences. People tend to prefer goods that cost more money and assume that such expensive goods will be more effective, even in cases where the price of the good is itself arbitrary. Although much work has documented the existence of these pricing effects, unfortunately little work has addressed where these price effects come from in the first place. Here we use a comparative approach to distinguish between different accounts of this bias and to explore the origins of these effects. Specifically, we test whether brown capuchin monkeys (Cebus apella are also susceptible to pricing effects within the context of an experimentally trained token economy. Using a capuchin population previously trained in a token market, we explored whether monkeys used price as an indicator of value across four experiments. Although monkeys demonstrated an understanding of which goods had which prices (consistently shifting preferences to cheaper goods when prices were increased, we observed no evidence that such price information affected their valuation of different kinds of goods. These results suggest that human price effects may involve more sophisticated human-unique cognitive capacities, such as an understanding of market forces and signaling.

  10. Capuchin monkeys do not show human-like pricing effects.

    Science.gov (United States)

    Catapano, Rhia; Buttrick, Nicholas; Widness, Jane; Goldstein, Robin; Santos, Laurie R

    2014-01-01

    Recent work in judgment and decision-making has shown that a good's price can have irrational effects on people's preferences. People tend to prefer goods that cost more money and assume that such expensive goods will be more effective, even in cases where the price of the good is itself arbitrary. Although much work has documented the existence of these pricing effects, unfortunately little work has addressed where these price effects come from in the first place. Here we use a comparative approach to distinguish between different accounts of this bias and to explore the origins of these effects. Specifically, we test whether brown capuchin monkeys (Cebus apella) are also susceptible to pricing effects within the context of an experimentally trained token economy. Using a capuchin population previously trained in a token market, we explored whether monkeys used price as an indicator of value across four experiments. Although monkeys demonstrated an understanding of which goods had which prices (consistently shifting preferences to cheaper goods when prices were increased), we observed no evidence that such price information affected their valuation of different kinds of goods. These results suggest that human pricing effects may involve more sophisticated human-unique cognitive capacities, such as an understanding of market forces and signaling.

  11. Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes.

    Science.gov (United States)

    Baxter, Melissa; Withey, Sarah; Harrison, Sean; Segeritz, Charis-Patricia; Zhang, Fang; Atkinson-Dell, Rebecca; Rowe, Cliff; Gerrard, Dave T; Sison-Young, Rowena; Jenkins, Roz; Henry, Joanne; Berry, Andrew A; Mohamet, Lisa; Best, Marie; Fenwick, Stephen W; Malik, Hassan; Kitteringham, Neil R; Goldring, Chris E; Piper Hanley, Karen; Vallier, Ludovic; Hanley, Neil A

    2015-03-01

    Hepatocyte-like cells (HLCs), differentiated from pluripotent stem cells by the use of soluble factors, can model human liver function and toxicity. However, at present HLC maturity and whether any deficit represents a true fetal state or aberrant differentiation is unclear and compounded by comparison to potentially deteriorated adult hepatocytes. Therefore, we generated HLCs from multiple lineages, using two different protocols, for direct comparison with fresh fetal and adult hepatocytes. Protocols were developed for robust differentiation. Multiple transcript, protein and functional analyses compared HLCs to fresh human fetal and adult hepatocytes. HLCs were comparable to those of other laboratories by multiple parameters. Transcriptional changes during differentiation mimicked human embryogenesis and showed more similarity to pericentral than periportal hepatocytes. Unbiased proteomics demonstrated greater proximity to liver than 30 other human organs or tissues. However, by comparison to fresh material, HLC maturity was proven by transcript, protein and function to be fetal-like and short of the adult phenotype. The expression of 81% phase 1 enzymes in HLCs was significantly upregulated and half were statistically not different from fetal hepatocytes. HLCs secreted albumin and metabolized testosterone (CYP3A) and dextrorphan (CYP2D6) like fetal hepatocytes. In seven bespoke tests, devised by principal components analysis to distinguish fetal from adult hepatocytes, HLCs from two different source laboratories consistently demonstrated fetal characteristics. HLCs from different sources are broadly comparable with unbiased proteomic evidence for faithful differentiation down the liver lineage. This current phenotype mimics human fetal rather than adult hepatocytes. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  12. Showing Off in Humans: Male Generosity as a Mating Signal

    Directory of Open Access Journals (Sweden)

    Wendy Iredale

    2008-07-01

    Full Text Available We examined people's charity contributions while in the presence of an observer of the same sex, opposite sex, or no observer. Inspired by costly signaling theory, we hypothesized that men would be more generous in the presence of a potential mate. Men and women played a number of experimental games in which they could earn money. On completion of these games participants were asked what percentage of their earned money they would be willing to donate to charity. Our results show that men contribute more to charity when observed by a member of the opposite sex than by a member of the same sex or no observer. Conversely, female charity donations did not significantly vary across the three observer conditions. Findings support the notion that men's generosity might have evolved as a mating signal.

  13. A human protein interaction network shows conservation of aging processes between human and invertebrate species.

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    Russell Bell

    2009-03-01

    Full Text Available We have mapped a protein interaction network of human homologs of proteins that modify longevity in invertebrate species. This network is derived from a proteome-scale human protein interaction Core Network generated through unbiased high-throughput yeast two-hybrid searches. The longevity network is composed of 175 human homologs of proteins known to confer increased longevity through loss of function in yeast, nematode, or fly, and 2,163 additional human proteins that interact with these homologs. Overall, the network consists of 3,271 binary interactions among 2,338 unique proteins. A comparison of the average node degree of the human longevity homologs with random sets of proteins in the Core Network indicates that human homologs of longevity proteins are highly connected hubs with a mean node degree of 18.8 partners. Shortest path length analysis shows that proteins in this network are significantly more connected than would be expected by chance. To examine the relationship of this network to human aging phenotypes, we compared the genes encoding longevity network proteins to genes known to be changed transcriptionally during aging in human muscle. In the case of both the longevity protein homologs and their interactors, we observed enrichments for differentially expressed genes in the network. To determine whether homologs of human longevity interacting proteins can modulate life span in invertebrates, homologs of 18 human FRAP1 interacting proteins showing significant changes in human aging muscle were tested for effects on nematode life span using RNAi. Of 18 genes tested, 33% extended life span when knocked-down in Caenorhabditis elegans. These observations indicate that a broad class of longevity genes identified in invertebrate models of aging have relevance to human aging. They also indicate that the longevity protein interaction network presented here is enriched for novel conserved longevity proteins.

  14. Co-residence patterns in hunter-gatherer societies show unique human social structure.

    Science.gov (United States)

    Hill, Kim R; Walker, Robert S; Bozicević, Miran; Eder, James; Headland, Thomas; Hewlett, Barry; Hurtado, A Magdalena; Marlowe, Frank; Wiessner, Polly; Wood, Brian

    2011-03-11

    Contemporary humans exhibit spectacular biological success derived from cumulative culture and cooperation. The origins of these traits may be related to our ancestral group structure. Because humans lived as foragers for 95% of our species' history, we analyzed co-residence patterns among 32 present-day foraging societies (total n = 5067 individuals, mean experienced band size = 28.2 adults). We found that hunter-gatherers display a unique social structure where (i) either sex may disperse or remain in their natal group, (ii) adult brothers and sisters often co-reside, and (iii) most individuals in residential groups are genetically unrelated. These patterns produce large interaction networks of unrelated adults and suggest that inclusive fitness cannot explain extensive cooperation in hunter-gatherer bands. However, large social networks may help to explain why humans evolved capacities for social learning that resulted in cumulative culture.

  15. Astrocytes from adult Wistar rats aged in vitro show changes in glial functions.

    Science.gov (United States)

    Souza, Débora Guerini; Bellaver, Bruna; Raupp, Gustavo Santos; Souza, Diogo Onofre; Quincozes-Santos, André

    2015-11-01

    Astrocytes, the most versatile cells of the central nervous system, play an important role in the regulation of neurotransmitter homeostasis, energy metabolism, antioxidant defenses and the anti-inflammatory response. Recently, our group characterized cortical astrocyte cultures from adult Wistar rats. In line with that work, we studied glial function using an experimental in vitro model of aging astrocytes (30 days in vitro after reaching confluence) from newborn (NB), adult (AD) and aged (AG) Wistar rats. We evaluated metabolic parameters, such as the glucose uptake, glutamine synthetase (GS) activity, and glutathione (GSH) content, as well as the GFAP, GLUT-1 and xCT expression. AD and AG astrocytes take up less glucose than NB astrocytes and had decreased GLUT1 expression levels. Furthermore, AD and AG astrocytes exhibited decreased GS activity compared to NB cells. Simultaneously, AD and AG astrocytes showed an increase in GSH levels, along with an increase in xCT expression. NB, AD and AG astrocytes presented similar morphology; however, differences in GFAP levels were observed. Taken together, these results improve the knowledge of cerebral senescence and represent an innovative tool for brain studies of aging. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies.

    Science.gov (United States)

    Méplan, Catherine; Johnson, Ian T; Polley, Abigael C J; Cockell, Simon; Bradburn, David M; Commane, Daniel M; Arasaradnam, Ramesh P; Mulholland, Francis; Zupanic, Anze; Mathers, John C; Hesketh, John

    2016-08-01

    Epidemiologic studies highlight the potential role of dietary selenium (Se) in colorectal cancer prevention. Our goal was to elucidate whether expression of factors crucial for colorectal homoeostasis is affected by physiologic differences in Se status. Using transcriptomics and proteomics followed by pathway analysis, we identified pathways affected by Se status in rectal biopsies from 22 healthy adults, including 11 controls with optimal status (mean plasma Se = 1.43 μM) and 11 subjects with suboptimal status (mean plasma Se = 0.86 μM). We observed that 254 genes and 26 proteins implicated in cancer (80%), immune function and inflammatory response (40%), cell growth and proliferation (70%), cellular movement, and cell death (50%) were differentially expressed between the 2 groups. Expression of 69 genes, including selenoproteins W1 and K, which are genes involved in cytoskeleton remodelling and transcription factor NFκB signaling, correlated significantly with Se status. Integrating proteomics and transcriptomics datasets revealed reduced inflammatory and immune responses and cytoskeleton remodelling in the suboptimal Se status group. This is the first study combining omics technologies to describe the impact of differences in Se status on colorectal expression patterns, revealing that suboptimal Se status could alter inflammatory signaling and cytoskeleton in human rectal mucosa and so influence cancer risk.-Méplan, C., Johnson, I. T., Polley, A. C. J., Cockell, S., Bradburn, D. M., Commane, D. M., Arasaradnam, R. P., Mulholland, F., Zupanic, A., Mathers, J. C., Hesketh, J. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies. © The Author(s).

  17. 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....

  18. Older Adults Show Deficits in Retrieving and Decoding Associative Mediators Generated at Study

    Science.gov (United States)

    Hertzog, Christopher; Fulton, Erika K.; Mandviwala, Lulua; Dunlosky, John

    2013-01-01

    We instructed the use of mediators to encode paired-associate items, and then measured both cued recall of targets and mediators. Older adults (n = 49) and younger adults (n = 57) studied a mixed list of concrete and abstract noun pairs under instructions to either generate a sentence or an image to form a new association between normatively…

  19. Plasma and serum lipidomics of healthy white adults shows characteristic profiles by subjects' gender and age.

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    Masaki Ishikawa

    Full Text Available Blood is a commonly used biofluid for biomarker discovery. Although blood lipid metabolites are considered to be potential biomarker candidates, their fundamental properties are not well characterized. We aimed to (1 investigate the matrix type (serum vs. plasma that may be preferable for lipid biomarker exploration, (2 elucidate age- and gender-associated differences in lipid metabolite levels, and (3 examine the stability of lipid metabolites in matrix samples subjected to repeated freeze-thaw cycles. Using liquid chromatography-mass spectrometry, we performed lipidomic analyses for fasting plasma and serum samples for four groups (15 subjects/group of young and elderly (25-34 and 55-64 years old, respectively males and females and for an additional aliquot of samples from young males, which were subjected to repeated freeze-thaw cycles. Lysophosphatidylcholine and diacylglycerol levels were higher in serum than in plasma samples, suggesting that the clotting process influences serum lipid metabolite levels. Gender-associated differences highlighted that the levels of many sphingomyelin species were significantly higher in females than in males, irrespective of age and matrix (plasma and serum. Age-associated differences were more prominent in females than in males, and in both matrices, levels of many triacylglycerols were significantly higher in elderly females than in young females. Plasma and serum levels of most lipid metabolites were reduced by freeze-thawing. Our results indicate that plasma is an optimal matrix for exploring lipid biomarkers because it represents the original properties of an individual's blood sample. In addition, the levels of some blood lipid species of healthy adults showed gender- and age-associated differences; thus, this should be considered during biomarker exploration and its application in diagnostics. Our fundamental findings on sample selection and handling procedures for measuring blood lipid metabolites

  20. Adults and children with high imagery show more pronounced perceptual priming effect.

    Science.gov (United States)

    Hatakeyama, T

    1997-06-01

    36 children in Grade 5 and 59 university students, all native speakers of Japanese, studied three types of priming stimuli in a mixed list: words written in hiragana (Japanese syllabary used in writing), words written in kanji (Chinese characters also used in writing), and pictures. They were then given a task involving completion of hiragana-word fragments: the task involved studied and nonstudied items. For both children and university students, words in hiragana produced the largest priming effects, that is, the words that had appeared in hiragana in the preceding study phase were generated more often in the test phase of word completion than the other two types of priming stimuli. This confirms that the perceptual priming effect depends much on data-driven processing. For both age groups, words in kanji produced nearly half the priming effects seen for hiragana-words. On the other hand, pictures had no priming effect for children but they had a similar effect to kanji-words for students. The discrepancy between kanji-words and pictures for children suggests that the former force the subject to read the words, which, possibly, activates the hiragana-words, while the latter do not necessarily force labelling the pictures. Among three kinds of imagery tests, the Verbalizer-Visualizer Questionnaire predicted priming scores for children and the Questionnaire upon Mental Imagery did so for students, but the Test of Visual Imagery Control did not predict the scores for either age group. This shows that children reporting habitual use of imagery and adults reporting vivid imagery have more pronounced perceptual priming effects. We conclude that the imagery ability based on self-judgments reflects real characteristics of the perceptual representation system of Tulving and Schacter (1990).

  1. Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement

    OpenAIRE

    Cideciyan, Artur V.; Jacobson, Samuel G.; Beltran, William A.; Sumaroka, Alexander; Swider, Malgorzata; Iwabe, Simone; Roman, Alejandro J.; Olivares, Melani B.; Schwartz, Sharon B.; Komáromy, András M.; Hauswirth, William W.; Aguirre, Gustavo D.

    2013-01-01

    The first retinal gene therapy in human blindness from RPE65 mutations has focused on safety and efficacy, as defined by improved vision. The disease component not studied, however, has been the fate of photoreceptors in this progressive retinal degeneration. We show that gene therapy improves vision for at least 3 y, but photoreceptor degeneration progresses unabated in humans. In the canine model, the same result occurs when treatment is at the disease stage equivalent to humans. The study ...

  2. 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 .

  3. Young Adults with Autism Spectrum Disorder Show Early Atypical Neural Activity during Emotional Face Processing

    Directory of Open Access Journals (Sweden)

    Rachel C. Leung

    2018-02-01

    Full Text Available Social cognition is impaired in autism spectrum disorder (ASD. The ability to perceive and interpret affect is integral to successful social functioning and has an extended developmental course. However, the neural mechanisms underlying emotional face processing in ASD are unclear. Using magnetoencephalography (MEG, the present study explored neural activation during implicit emotional face processing in young adults with and without ASD. Twenty-six young adults with ASD and 26 healthy controls were recruited. Participants indicated the location of a scrambled pattern (target that was presented alongside a happy or angry face. Emotion-related activation sources for each emotion were estimated using the Empirical Bayes Beamformer (pcorr ≤ 0.001 in Statistical Parametric Mapping 12 (SPM12. Emotional faces elicited elevated fusiform, amygdala and anterior insula and reduced anterior cingulate cortex (ACC activity in adults with ASD relative to controls. Within group comparisons revealed that angry vs. happy faces elicited distinct neural activity in typically developing adults; there was no distinction in young adults with ASD. Our data suggest difficulties in affect processing in ASD reflect atypical recruitment of traditional emotional processing areas. These early differences may contribute to difficulties in deriving social reward from faces, ascribing salience to faces, and an immature threat processing system, which collectively could result in deficits in emotional face processing.

  4. The plasma virome of febrile adult Kenyans shows frequent parvovirus B19 infections and a novel arbovirus (Kadipiro virus).

    Science.gov (United States)

    Ngoi, Carolyne N; Siqueira, Juliana; Li, Linlin; Deng, Xutao; Mugo, Peter; Graham, Susan M; Price, Matt A; Sanders, Eduard J; Delwart, Eric

    2016-12-01

    Viral nucleic acids present in the plasma of 498 Kenyan adults with unexplained fever were characterized by metagenomics analysis of 51 sample pools. The highest to lowest fraction of plasma pools was positive for parvovirus B19 (75 %), pegivirus C (GBV-C) (67 %), alpha anellovirus (59 %), gamma anellovirus (55 %), beta anellovirus (41 %), dengue virus genotype 2 (DENV-2) (16 %), human immunodeficiency virus type 1 (6 %), human herpesvirus 6 (6 %), HBV (4 %), rotavirus (4 %), hepatitis B virus (4 %), rhinovirus C (2 %), Merkel cell polyomavirus (MCPyV; 2 %) and Kadipiro virus (2 %). Ranking by overall percentage of viral reads yielded similar results. Characterization of viral nucleic acids in the plasma of a febrile East African population showed a high frequency of parvovirus B19 and DENV infections and detected a reovirus (Kadipiro virus) previously reported only in Asian Culex mosquitoes, providing a baseline to compare with future virome studies to detect emerging viruses in this region.

  5. Hunted woolly monkeys (Lagothrix poeppigii show threat-sensitive responses to human presence.

    Directory of Open Access Journals (Sweden)

    Sarah Papworth

    Full Text Available Responding only to individuals of a predator species which display threatening behaviour allows prey species to minimise energy expenditure and other costs of predator avoidance, such as disruption of feeding. The threat sensitivity hypothesis predicts such behaviour in prey species. If hunted animals are unable to distinguish dangerous humans from non-dangerous humans, human hunting is likely to have a greater effect on prey populations as all human encounters should lead to predator avoidance, increasing stress and creating opportunity costs for exploited populations. We test the threat sensitivity hypothesis in wild Poeppigi's woolly monkeys (Lagothrix poeppigii in Yasuní National Park, Ecuador, by presenting human models engaging in one of three behaviours "hunting", "gathering" or "researching". These experiments were conducted at two sites with differing hunting pressures. Visibility, movement and vocalisations were recorded and results from two sites showed that groups changed their behaviours after being exposed to humans, and did so in different ways depending on the behaviour of the human model. Results at the site with higher hunting pressure were consistent with predictions based on the threat sensitivity hypothesis. Although results at the site with lower hunting pressure were not consistent with the results at the site with higher hunting pressure, groups at this site also showed differential responses to different human behaviours. These results provide evidence of threat-sensitive predator avoidance in hunted primates, which may allow them to conserve both time and energy when encountering humans which pose no threat.

  6. Boys with autism spectrum disorders show superior performance on the adult Embedded Figures Test

    NARCIS (Netherlands)

    Schlooz, W.A.J.M.; Hulstijn, W.

    2014-01-01

    Weak central coherence is frequently studied using the Embedded Figures Test (EFT) yielding mixed and ambiguous results. In this study, the performance of 36 boys (9–14 years) with Autism Spectrum Disorders (ASD) is compared with that of 46 typical peers using both the children's and the adult

  7. Do Adults with Mental Retardation Show Pictorial Superiority Effects in Recall and Recognition?

    Science.gov (United States)

    Cherry, Katie E.; Applegate, Heather; Reese, Celinda M.

    2002-01-01

    A study examined memory for pictures and words in 16 adults with mental retardation and 24 controls. Pictorial superiority effects occurred in free recall and recognition for both intelligence-level groups. Correlational analyses indicated working memory span was primarily related to recall performance, irrespective of stimulus format. (Contains…

  8. Swords and Pens. What the Military Can Show Us about Teaching Basic Skills to Young Adults.

    Science.gov (United States)

    Sticht, Thomas G.

    2000-01-01

    Describes how the military fights against illiteracy, suggesting military methods are useful in teaching young adult civilians. Highlights: the origins of functional context education in the military; work toward literacy in the Vietnam war era; applications to teaching civilians; and the K-12 education system. Functional context education can…

  9. Do Adults Show an Effect of Delayed First Language Acquisition When Calculating Scalar Implicatures?

    Science.gov (United States)

    Davidson, Kathryn; Mayberry, Rachel I

    Language acquisition involves learning not only grammatical rules and a lexicon, but also what someone is intending to convey with their utterance: the semantic/pragmatic component of language. In this paper we separate the contributions of linguistic development and cognitive maturity to the acquisition of the semantic/pragmatic component of language by comparing deaf adults who had either early or late first exposure to their first language (ASL). We focus on the particular type of meaning at the semantic/pragmatic interface called scalar implicature , for which preschool-age children typically differ from adults. Children's behavior has been attributed to either their not knowing appropriate linguistic alternatives to consider or to cognitive developmental differences between children and adults. Unlike children, deaf adults with late language exposure are cognitively mature, although they never fully acquire some complex linguistic structures, and thus serve as a test for the role of language in such interpretations. Our results indicate an overall high performance by late learners, especially when implicatures are not based on conventionalized items. However, compared to early language learners, late language learners compute fewer implicatures when conventionalized linguistic alternatives are involved (e.g. ). We conclude that (i) in general, Gricean pragmatic reasoning does not seem to be impacted by delayed first language acquisition and can account for multiple quantity implicatures, but (ii) the creation of a scale based on lexical items can lead to ease in alternative creation that may be advantageously learned early in life, and that this may be one of several factors contributing to differences between adults and children on scalar implicature tasks.

  10. A humanized anti-M2 scFv shows protective in vitro activity against influenza

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M [Los Alamos National Laboratory; Velappan, Nileena [Los Alamos National Laboratory; Schmidt, Jurgen G [Los Alamos National Laboratory

    2008-01-01

    M2 is one of the most conserved influenza proteins, and has been widely prospected as a potential universal vaccine target, with protection predominantly mediated by antibodies. In this paper we describe the creation of a humanized single chain Fv from 14C2, a potent monoclonal antibody against M2. We show that the humanized scFv demonstrates similar activity to the parental mAb: it is able to recognize M2 in its native context on cell surfaces and is able to show protective in vitro activity against influenza, and so represents a potential lead antibody candidate for universal prophylactic or therapeutic intervention in influenza.

  11. Cell pattern in adult human corneal endothelium.

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. Cultural assemblages show nested structure in humans and chimpanzees but not orangutans.

    Science.gov (United States)

    Kamilar, Jason M; Atkinson, Quentin D

    2014-01-07

    The evolution of hominin culture is well-documented in the archeological and fossil record, but such a record is largely absent for nonhuman primates. An alternative approach to studying cultural evolution is to examine patterns of modern cultural variation. In this article we measure nestedness across human and great ape "cultural repertoires" to gain insight into the accumulation and maintenance of putative cultural diversity in these species. Cultural assemblages are nested if cultures with a small repertoire of traits tend to comprise a proper subset of those traits present in more complex cultures. This nesting will occur if some traits are sequentially gained or lost, which may be because of the differential dispersal or extinction of traits. Here we apply statistical tools from ecology to examine the degree of nestedness in four datasets documenting the presence or absence of specific cultural traits across indigenous human populations in North America and New Guinea. We then compare the human data to patterns observed for putative cultural traits in chimpanzee and orangutan populations. In both humans and chimpanzees, cultural diversity is highly nonrandom, showing significant nested structure for all of the datasets examined. We find no evidence for nestedness in the orangutan cultural data. These findings are consistent with a sequential "layering" of cultural diversity in humans and chimpanzees, but not orangutans. Such an interpretation implies that the traits required for sequential cultural evolution first appeared in the last common ancestor of chimpanzees and humans.

  14. MicroRNAs show mutually exclusive expression patterns in the brain of adult male rats

    DEFF Research Database (Denmark)

    Olsen, Line; Klausen, Mikkel; Helboe, Lone

    2009-01-01

    BACKGROUND: The brain is a major site of microRNA (miRNA) gene expression, but the spatial expression patterns of miRNAs within the brain have not yet been fully covered. METHODOLOGY/PRINCIPAL FINDINGS: We have characterized the regional expression profiles of miRNAs in five distinct regions...... of the adult rat brain: amygdala, cerebellum, hippocampus, hypothalamus and substantia nigra. Microarray profiling uncovered 48 miRNAs displaying more than three-fold enrichment between two or more brain regions. Notably, we found reciprocal expression profiles for a subset of the miRNAs predominantly found...... (> ten times) in either the cerebellum (miR-206 and miR-497) or the forebrain regions (miR-132, miR-212, miR-221 and miR-222). CONCLUSIONS/SIGNIFICANCE: The results indicate that some miRNAs could be important for area-specific functions in the brain. Our data, combined with previous studies in mice...

  15. Astrocitary niches in human adult medulla oblongata.

    Science.gov (United States)

    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.

  16. Characterization of motor units in behaving adult mice shows a wide primary range.

    Science.gov (United States)

    Ritter, Laura K; Tresch, Matthew C; Heckman, C J; Manuel, Marin; Tysseling, Vicki M

    2014-08-01

    The mouse is essential for genetic studies of motor function in both normal and pathological states. Thus it is important to consider whether the structure of motor output from the mouse is in fact analogous to that recorded in other animals. There is a striking difference in the basic electrical properties of mouse motoneurons compared with those in rats, cats, and humans. The firing evoked by injected currents produces a unique frequency-current (F-I) function that emphasizes recruitment of motor units at their maximum force. These F-I functions, however, were measured in anesthetized preparations that lacked two key components of normal synaptic input: high levels of synaptic noise and neuromodulatory inputs. Recent studies suggest that the alterations in the F-I function due to these two components are essential for recreating firing behavior of motor units in human subjects. In this study we provide the first data on firing patterns of motor units in the awake mouse, focusing on steady output in quiet stance. The resulting firing patterns did not match the predictions from the mouse F-I behaviors but instead revealed rate modulation across a remarkably wide range (10-60 Hz). The low end of the firing range may be due to changes in the F-I relation induced by synaptic noise and neuromodulatory inputs. The high end of the range may indicate that, unlike other species, quiet standing in the mouse involves recruitment of relatively fast-twitch motor units. Copyright © 2014 the American Physiological Society.

  17. Comparative Serum Challenges Show Divergent Patterns of Gene Expression and Open Chromatin in Human and Chimpanzee.

    Science.gov (United States)

    Pizzollo, Jason; Nielsen, William J; Shibata, Yoichiro; Safi, Alexias; Crawford, Gregory E; Wray, Gregory A; Babbitt, Courtney C

    2018-03-01

    Humans experience higher rates of age-associated diseases than our closest living evolutionary relatives, chimpanzees. Environmental factors can explain many of these increases in disease risk, but species-specific genetic changes can also play a role. Alleles that confer increased disease susceptibility later in life can persist in a population in the absence of selective pressure if those changes confer positive adaptation early in life. One age-associated disease that disproportionately affects humans compared with chimpanzees is epithelial cancer. Here, we explored genetic differences between humans and chimpanzees in a well-defined experimental assay that mimics gene expression changes that happen during cancer progression: A fibroblast serum challenge. We used this assay with fibroblasts isolated from humans and chimpanzees to explore species-specific differences in gene expression and chromatin state with RNA-Seq and DNase-Seq. Our data reveal that human fibroblasts increase expression of genes associated with wound healing and cancer pathways; in contrast, chimpanzee gene expression changes are not concentrated around particular functional categories. Chromatin accessibility dramatically increases in human fibroblasts, yet decreases in chimpanzee cells during the serum response. Many regions of opening and closing chromatin are in close proximity to genes encoding transcription factors or genes involved in wound healing processes, further supporting the link between changes in activity of regulatory elements and changes in gene expression. Together, these expression and open chromatin data show that humans and chimpanzees have dramatically different responses to the same physiological stressor, and how a core physiological process can evolve quickly over relatively short evolutionary time scales.

  18. 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.

  19. Adult Education & Human Resource Development: Overlapping and Disparate Fields

    Science.gov (United States)

    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…

  20. Self-compassionate young adults show lower salivary alpha-amylase responses to repeated psychosocial stress.

    Science.gov (United States)

    Breines, Juliana G; McInnis, Christine M; Kuras, Yuliya I; Thoma, Myriam V; Gianferante, Danielle; Hanlin, Luke; Chen, Xuejie; Rohleder, Nicolas

    2015-10-01

    In this study we tested the hypothesis that participants higher in dispositional self-compassion would show lower stress-induced reactivity of salivary alpha-amylase (sAA), a marker of sympathetic nervous system activation. Thirty-three healthy participants (18-34 years old) were exposed to a standardized laboratory stressor on two consecutive days. Self-compassion, self-esteem, and demographic factors were assessed by questionnaire and sAA was assessed at baseline and at 1, 10, 30, and 60 minutes following each stressor. Self-compassion was a significant negative predictor of sAA responses on both days. This relationship remained significant when controlling for self-esteem, subjective distress, age, gender, ethnicity, and Body Mass Index (BMI). These results suggest that self-compassion may serve as a protective factor against stress-induced physiological changes that have implications for health.

  1. Yeast-2-Hybrid data file showing progranulin interactions in human fetal brain and bone marrow libraries

    Directory of Open Access Journals (Sweden)

    Irmgard Tegeder

    2016-12-01

    Full Text Available Progranulin deficiency in humans is associated with neurodegeneration. Its mechanisms are not yet fully understood. We performed a Yeast-2-Hybrid screen using human full-length progranulin as bait to assess the interactions of progranulin. Progranulin was screened against human fetal brain and human bone marrow libraries using the standard Matchmaker technology (Clontech. This article contains the full Y2H data table, including blast results and sequences, a sorted table according to selection criteria for likely positive, putatively positive, likely false and false preys, and tables showing the gene ontology terms associated with the likely and putative preys of the brain and bone marrow libraries. The interactions with autophagy proteins were confirmed and functionally analyzed in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016 [1].

  2. Yeast-2-Hybrid data file showing progranulin interactions in human fetal brain and bone marrow libraries.

    Science.gov (United States)

    Tegeder, Irmgard

    2016-12-01

    Progranulin deficiency in humans is associated with neurodegeneration. Its mechanisms are not yet fully understood. We performed a Yeast-2-Hybrid screen using human full-length progranulin as bait to assess the interactions of progranulin. Progranulin was screened against human fetal brain and human bone marrow libraries using the standard Matchmaker technology (Clontech). This article contains the full Y2H data table, including blast results and sequences, a sorted table according to selection criteria for likely positive, putatively positive, likely false and false preys, and tables showing the gene ontology terms associated with the likely and putative preys of the brain and bone marrow libraries. The interactions with autophagy proteins were confirmed and functionally analyzed in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016) [1].

  3. Dihydrochalcone Compounds Isolated from Crabapple Leaves Showed Anticancer Effects on Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Xiaoxiao Qin

    2015-11-01

    Full Text Available Seven dihydrochalcone compounds were isolated from the leaves of Malus crabapples, cv. “Radiant”, and their chemical structures were elucidated by UV, IR, ESI-MS, 1H-NMR and 13C-NMR analyses. These compounds, which include trilobatin (A1, phloretin (A2, 3-hydroxyphloretin (A3, phloretin rutinoside (A4, phlorizin (A5, 6′′-O-coumaroyl-4′-O-glucopyranosylphloretin (A6, and 3′′′-methoxy-6′′-O-feruloy-4′-O-glucopyranosyl-phloretin (A7, all belong to the phloretin class and its derivatives. Compounds A6 and A7 are two new rare dihydrochalcone compounds. The results of a MTT cancer cell growth inhibition assay demonstrated that phloretin and these derivatives showed significant positive anticancer activities against several human cancer cell lines, including the A549 human lung cancer cell line, Bel 7402 liver cancer cell line, HepG2 human ileocecal cancer cell line, and HT-29 human colon cancer cell line. A7 had significant effects on all cancer cell lines, suggesting potential applications for phloretin and its derivatives. Adding a methoxyl group to phloretin dramatically increases phloretin’s anticancer activity.

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

    Science.gov (United States)

    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.

  5. Ninety-six hours to build a prototype robot showing human emotions

    CERN Multimedia

    Stefania Pandolfi

    2016-01-01

    Thirty-five Master's students in the fields of business, design and engineering participated in an intensive five-day project-based introduction to programming and advanced electronics. The goal of the initiative was to build a fully functional prototype robot able to communicate and show at least four basic human emotions.    A group of students is presenting a prototype robot showing human emotions at IdeaSquare. With no previous experience in electronics or coding, groups of students from Portugal, Italy, Norway and Estonia were introduced to the basics of sensors, integrated circuits and actuators, and after just 96 hours they presented their functioning robots at IdeaSquare on Friday, 15 January. These robots, mostly built around Arduino boards and recycled materials, were able to display different human emotions as a response to external environmental inputs. The five-day workshop, called öBot, was organised by the IdeaSquare te...

  6. Variance decomposition shows the importance of human-climate feedbacks in the Earth system

    Science.gov (United States)

    Calvin, K. V.; Bond-Lamberty, B. P.; Jones, A. D.; Shi, X.; Di Vittorio, A. V.; Thornton, P. E.

    2017-12-01

    The human and Earth systems are intricately linked: climate influences agricultural production, renewable energy potential, and water availability, for example, while anthropogenic emissions from industry and land use change alter temperature and precipitation. Such feedbacks have the potential to significantly alter future climate change. Current climate change projections contain significant uncertainties, however, and because Earth System Models do not generally include dynamic human (demography, economy, energy, water, land use) components, little is known about how climate feedbacks contribute to that uncertainty. Here we use variance decomposition of a novel coupled human-earth system model to show that the influence of human-climate feedbacks can be as large as 17% of the total variance in the near term for global mean temperature rise, and 11% in the long term for cropland area. The near-term contribution of energy and land use feedbacks to the climate on global mean temperature rise is as large as that from model internal variability, a factor typically considered in modeling studies. Conversely, the contribution of climate feedbacks to cropland extent, while non-negligible, is less than that from socioeconomics, policy, or model. Previous assessments have largely excluded these feedbacks, with the climate community focusing on uncertainty due to internal variability, scenario, and model and the integrated assessment community focusing on uncertainty due to socioeconomics, technology, policy, and model. Our results set the stage for a new generation of models and hypothesis testing to determine when and how bidirectional feedbacks between human and Earth systems should be considered in future assessments of climate change.

  7. An acid phosphatase in the plasma membranes of human astrocytoma showing marked specificity toward phosphotyrosine protein.

    Science.gov (United States)

    Leis, J F; Kaplan, N O

    1982-11-01

    The plasma membrane from the human tumor astrocytoma contains an active acid phosphatase activity based on hydrolysis of p-nitrophenyl phosphate. Other acid phosphatase substrates--beta-glycerophosphate, O-phosphorylcholine, and 5'-AMP--are not hydrolyzed significantly. The phosphatase activity is tartrate insensitive and is stimulated by Triton X-100 and EDTA. Of the three known phosphoamino acids, only free O-phosphotyrosine is hydrolyzed by the membrane phosphatase activity. Other acid phosphatases tested from potato, wheat germ, milk, and bovine prostate did not show this degree of specificity. The plasma membrane activity also dephosphorylated phosphotyrosine histone at a much greater rate than did the other acid phosphatases. pH profiles for free O-phosphotyrosine and phosphotyrosine histone showed a shift toward physiological pH, indicating possible physiological significance. Phosphotyrosine histone dephosphorylation activity was nearly 10 times greater than that seen for phosphoserine histone dephosphorylation, and Km values were much lower for phosphotyrosine histone dephosphorylation (0.5 microM vs. 10 microM). Fluoride and zinc significantly inhibited phosphoserine histone dephosphorylation. Vanadate, on the other hand, was a potent inhibitor of phosphotyrosine histone dephosphorylation (50% inhibition at 0.5 microM) but not of phosphoserine histone. ATP stimulated phosphotyrosine histone dephosphorylation (160-250%) but inhibited phosphoserine histone dephosphorylation (95%). These results suggest the existence of a highly specific phosphotyrosine protein phosphatase activity associated with the plasma membrane of human astrocytoma.

  8. Early reversal cells in adult human bone remodeling

    DEFF Research Database (Denmark)

    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...

  9. A single-nucleotide polymorphism of human neuropeptide s gene originated from Europe shows decreased bioactivity.

    Directory of Open Access Journals (Sweden)

    Cheng Deng

    Full Text Available Using accumulating SNP (Single-Nucleotide Polymorphism data, we performed a genome-wide search for polypeptide hormone ligands showing changes in the mature regions to elucidate genotype/phenotype diversity among various human populations. Neuropeptide S (NPS, a brain peptide hormone highly conserved in vertebrates, has diverse physiological effects on anxiety, fear, hyperactivity, food intake, and sleeping time through its cognate receptor-NPSR. Here, we report a SNP rs4751440 (L(6-NPS causing non-synonymous substitution on the 6(th position (V to L of the NPS mature peptide region. L(6-NPS has a higher allele frequency in Europeans than other populations and probably originated from European ancestors ~25,000 yrs ago based on haplotype analysis and Approximate Bayesian Computation. Functional analyses indicate that L(6-NPS exhibits a significant lower bioactivity than the wild type NPS, with ~20-fold higher EC50 values in the stimulation of NPSR. Additional evolutionary and mutagenesis studies further demonstrate the importance of the valine residue in the 6(th position for NPS functions. Given the known physiological roles of NPS receptor in inflammatory bowel diseases, asthma pathogenesis, macrophage immune responses, and brain functions, our study provides the basis to elucidate NPS evolution and signaling diversity among human populations.

  10. Human active X-specific DNA methylation events showing stability across time and tissues

    Science.gov (United States)

    Joo, Jihoon Eric; Novakovic, Boris; Cruickshank, Mark; Doyle, Lex W; Craig, Jeffrey M; Saffery, Richard

    2014-01-01

    The phenomenon of X chromosome inactivation in female mammals is well characterised and remains the archetypal example of dosage compensation via monoallelic expression. The temporal series of events that culminates in inactive X-specific gene silencing by DNA methylation has revealed a ‘patchwork' of gene inactivation along the chromosome, with approximately 15% of genes escaping. Such genes are therefore potentially subject to sex-specific imbalance between males and females. Aside from XIST, the non-coding RNA on the X chromosome destined to be inactivated, very little is known about the extent of loci that may be selectively silenced on the active X chromosome (Xa). Using longitudinal array-based DNA methylation profiling of two human tissues, we have identified specific and widespread active X-specific DNA methylation showing stability over time and across tissues of disparate origin. Our panel of X-chromosome loci subject to methylation on Xa reflects a potentially novel mechanism for controlling female-specific X inactivation and sex-specific dimorphisms in humans. Further work is needed to investigate these phenomena. PMID:24713664

  11. 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)

  12. 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.

  13. 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...

  14. Functional measures show improvements after a home exercise program following supervised balance training in older adults with elevated fall risk.

    Science.gov (United States)

    Tisher, Kristen; Mann, Kimberly; VanDyke, Sarah; Johansson, Charity; Vallabhajosula, Srikant

    2018-03-05

    Supervised balance training shows immediate benefit for older adults at fall risk. The long-term effectiveness of such training can be enhanced by implementing a safe and simple home exercise program (HEP). We investigated the effects of a12-week unsupervised HEP following supervised clinic-based balance training on functional mobility, balance, fall risk, and gait. Six older adults with an elevated fall risk obtained an HEP and comprised the HEP group (HEPG) and five older adults who were not given an HEP comprised the no HEP group (NoHEPG). The HEP consisted of three static balance exercises: feet-together, single-leg stance, and tandem. Each exercise was to be performed twice for 30-60 s, once per day, 3 days per week for 12 weeks. Participants were educated on proper form, safety, and progression of exercises. Pre- and post-HEP testing included Berg Balance Scale (BBS), Timed Up and Go, Short Physical Performance Battery (SPPB) assessments, Activities-Balance Confidence, Late-Life Functional Disability Instrument and instrumented assessments of balance and gait (Limits of Stability, modified Clinical Test of Sensory Interaction on Balance, Gait). A healthy control group (HCG; n = 11) was also tested. For most of the measures, the HEPG improved to the level of HCG. Though task-specific improvements like BBS and SPPB components were seen, the results did not carry over to more dynamic assessments. Results provide proof of concept that a simple HEP can be independently implemented and effective for sustaining and/or improving balance in older adults at elevated fall-risk after they have undergone a clinic-based balance intervention.

  15. Human Zoos or Ethnic Shows? Essence and contingency in Living Ethnological Exhibitons

    Directory of Open Access Journals (Sweden)

    Sánchez-Gómez, Luis A.

    2013-12-01

    Full Text Available The aim of this article is to study the living ethnological exhibitions. The main feature of these multiform varieties of public show, which became widespread in late-nineteenth and early-twentieth century Europe and the United States, was the live presence of individuals who were considered “primitive”. Whilst these native peoples sometimes gave demonstrations of their skills or produced manufactures for the audience, more often their role was simply as exhibits, to display their bodies and gestures, their different and singular condition. In this article, the three main forms of modern ethnic show (commercial, colonial and missionary will be presented, together with a warning about the inadequacy of categorising all such spectacles under the label of “human zoos”, a term which has become common in both academic and media circles in recent years.El objetivo del artículo es estudiar las exhibiciones etnológicas vivas, una multiforme modalidad de espectáculo público que se extiende durante la segunda mitad del siglo XIX y la primera mitad del XX y que presenta como característica esencial la presentación “en vivo” de individuos considerados primitivos. Aunque tales personajes, los nativos, en ocasiones ejecutan ciertas destrezas o elaboran determinadas manufacturas de cara al público, lo más habitual es que su único cometido sea mostrarse a sí mismos, exhibir sus cuerpos y sus gestos, su condición diferente y singular. Revisamos las tres principales formas de show étnico moderno (comercial, colonial y misional y advertimos sobre lo inadecuado de englobar todos estos espectáculos bajo el calificativo de “zoos humanos”, expresión que se ha extendido tanto en el ámbito académico como en el mediático durante los últimos años.

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

    Science.gov (United States)

    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.

  17. Human small-cell lung cancers show amplification and expression of the N-myc gene

    International Nuclear Information System (INIS)

    Nau, M.M.; Brooks, B.J. Jr.; Carney, D.N.; Gazdar, A.F.; Battey, J.F.; Sausville, E.A.; Minna, J.D.

    1986-01-01

    The authors have found that 6 of 31 independently derived human small-cell lung cancer (SCLC) cell lines have 5- to 170-fold amplified N-myc gene sequences. The amplification is seen with probes from two separate exons of N-myc, which are homologous to either the second or the third exon of the c-myc gene. Amplified N-myc sequences were found in a tumor cell line started prior to chemotherapy, in SCLC tumor samples harvested directly from tumor metastases at autopsy, and from a resected primary lung cancer. Several N-myc-amplified tumor cell lines also exhibited N-myc hybridizing fragments not in the germ-line position. In one patient's tumor, an additional amplitifed N-myc DNA fragment was observed and this fragment was heterogeneously distributed in liver metastases. In contrast to SCLC with neuroendocrine properties, no non-small-cell lung cancer lines examined were found to have N-myc amplification. Fragments encoding two N-myc exons also detect increased amounts of a 3.1-kilobase N-myc mRNA in N-myc-amplified SCLC lines and in one cell line that does not show N-myc gene amplification. Both DNA and RNA hybridization experiments, using a 32 P-labelled restriction probe, show that in any one SCLC cell line, only one myc-related gene is amplified and expressed. They conclude that N-myc amplification is both common and potentially significant in the tumorigenesis or tumor progression of SCLC

  18. SadA-Expressing Staphylococci in the Human Gut Show Increased Cell Adherence and Internalization.

    Science.gov (United States)

    Luqman, Arif; Nega, Mulugeta; Nguyen, Minh-Thu; Ebner, Patrick; Götz, Friedrich

    2018-01-09

    A subgroup of biogenic amines, the so-called trace amines (TAs), are produced by mammals and bacteria and can act as neuromodulators. In the genus Staphylococcus, certain species are capable of producing TAs through the activity of staphylococcal aromatic amino acid decarboxylase (SadA). SadA decarboxylates aromatic amino acids to produce TAs, as well as dihydroxy phenylalanine and 5-hydroxytryptophan to thus produce the neurotransmitters dopamine and serotonin. SadA-expressing staphylococci were prevalent in the gut of most probands, where they are part of the human intestinal microflora. Furthermore, sadA-expressing staphylococci showed increased adherence to HT-29 cells and 2- to 3-fold increased internalization. Internalization and adherence was also increased in a sadA mutant in the presence of tryptamine. The α2-adrenergic receptor is required for enhanced adherence and internalization. Thus, staphylococci in the gut might contribute to gut activity and intestinal colonization. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. SadA-Expressing Staphylococci in the Human Gut Show Increased Cell Adherence and Internalization

    Directory of Open Access Journals (Sweden)

    Arif Luqman

    2018-01-01

    Full Text Available Summary: A subgroup of biogenic amines, the so-called trace amines (TAs, are produced by mammals and bacteria and can act as neuromodulators. In the genus Staphylococcus, certain species are capable of producing TAs through the activity of staphylococcal aromatic amino acid decarboxylase (SadA. SadA decarboxylates aromatic amino acids to produce TAs, as well as dihydroxy phenylalanine and 5-hydroxytryptophan to thus produce the neurotransmitters dopamine and serotonin. SadA-expressing staphylococci were prevalent in the gut of most probands, where they are part of the human intestinal microflora. Furthermore, sadA-expressing staphylococci showed increased adherence to HT-29 cells and 2- to 3-fold increased internalization. Internalization and adherence was also increased in a sadA mutant in the presence of tryptamine. The α2-adrenergic receptor is required for enhanced adherence and internalization. Thus, staphylococci in the gut might contribute to gut activity and intestinal colonization. : Luqman et al. examine the sadA gene and argue that it contributes to TAs. They found that neuromodulator-producing staphylococci were present in the gut of most probands. The produced neuromodulators enhanced the adherence and internalization of staphylococci to cells in culture. Keywords: adherence, aromatic amino acid decarboxylase, gut microbiota, internalization, neuromodulator, neurotransmitter, staphylococcus

  20. Human Commercial Models' Eye Colour Shows Negative Frequency-Dependent Selection.

    Directory of Open Access Journals (Sweden)

    Isabela Rodrigues Nogueira Forti

    Full Text Available In this study we investigated the eye colour of human commercial models registered in the UK (400 female and 400 male and Brazil (400 female and 400 male to test the hypothesis that model eye colour frequency was the result of negative frequency-dependent selection. The eye colours of the models were classified as: blue, brown or intermediate. Chi-square analyses of data for countries separated by sex showed that in the United Kingdom brown eyes and intermediate colours were significantly more frequent than expected in comparison to the general United Kingdom population (P<0.001. In Brazil, the most frequent eye colour brown was significantly less frequent than expected in comparison to the general Brazilian population. These results support the hypothesis that model eye colour is the result of negative frequency-dependent selection. This could be the result of people using eye colour as a marker of genetic diversity and finding rarer eye colours more attractive because of the potential advantage more genetically diverse offspring that could result from such a choice. Eye colour may be important because in comparison to many other physical traits (e.g., hair colour it is hard to modify, hide or disguise, and it is highly polymorphic.

  1. Tooth enamel oxygen "isoscapes" show a high degree of human mobility in prehistoric Britain.

    Science.gov (United States)

    Pellegrini, Maura; Pouncett, John; Jay, Mandy; Pearson, Mike Parker; Richards, Michael P

    2016-10-07

    A geostatistical model to predict human skeletal oxygen isotope values (δ 18 O p ) in Britain is presented here based on a new dataset of Chalcolithic and Early Bronze Age human teeth. The spatial statistics which underpin this model allow the identification of individuals interpreted as 'non-local' to the areas where they were buried (spatial outliers). A marked variation in δ 18 O p is observed in several areas, including the Stonehenge region, the Peak District, and the Yorkshire Wolds, suggesting a high degree of human mobility. These areas, rich in funerary and ceremonial monuments, may have formed focal points for people, some of whom would have travelled long distances, ultimately being buried there. The dataset and model represent a baseline for future archaeological studies, avoiding the complex conversions from skeletal to water δ 18 O values-a process known to be problematic.

  2. Tooth enamel oxygen “isoscapes” show a high degree of human mobility in prehistoric Britain

    Science.gov (United States)

    Pellegrini, Maura; Pouncett, John; Jay, Mandy; Pearson, Mike Parker; Richards, Michael P.

    2016-10-01

    A geostatistical model to predict human skeletal oxygen isotope values (δ18Op) in Britain is presented here based on a new dataset of Chalcolithic and Early Bronze Age human teeth. The spatial statistics which underpin this model allow the identification of individuals interpreted as ‘non-local’ to the areas where they were buried (spatial outliers). A marked variation in δ18Op is observed in several areas, including the Stonehenge region, the Peak District, and the Yorkshire Wolds, suggesting a high degree of human mobility. These areas, rich in funerary and ceremonial monuments, may have formed focal points for people, some of whom would have travelled long distances, ultimately being buried there. The dataset and model represent a baseline for future archaeological studies, avoiding the complex conversions from skeletal to water δ18O values-a process known to be problematic.

  3. Retinoblastoma pathway defects show differential ability to activate the constitutive DNA damage response in human tumorigenesis

    DEFF Research Database (Denmark)

    Tort, F.; Bartkova, J.; Sehested, M.

    2006-01-01

    culture models with differential defects of retinoblastoma pathway components, as overexpression of cyclin D1 or lack of p16(Ink4a), either alone or combined, did not elicit detectable DDR. In contrast, inactivation of pRb, the key component of the pathway, activated the DDR in cultured human or mouse...... with their hierarchical positions along the retinoblastoma pathway. Our data provide new insights into oncogene-evoked DDR in human tumorigenesis, with potential implications for individualized management of tumors with elevated cyclin D1 versus cyclin E, due to their distinct clinical variables and biological behavior....

  4. 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).

  5. An acid phosphatase in the plasma membranes of human astrocytoma showing marked specificity toward phosphotyrosine protein.

    OpenAIRE

    Leis, J F; Kaplan, N O

    1982-01-01

    The plasma membrane from the human tumor astrocytoma contains an active acid phosphatase activity based on hydrolysis of p-nitrophenyl phosphate. Other acid phosphatase substrates--beta-glycerophosphate, O-phosphorylcholine, and 5'-AMP--are not hydrolyzed significantly. The phosphatase activity is tartrate insensitive and is stimulated by Triton X-100 and EDTA. Of the three known phosphoamino acids, only free O-phosphotyrosine is hydrolyzed by the membrane phosphatase activity. Other acid pho...

  6. Electrotransfection and lipofection show comparable efficiency for in vitro gene delivery of primary human myoblasts.

    Science.gov (United States)

    Mars, Tomaz; Strazisar, Marusa; Mis, Katarina; Kotnik, Nejc; Pegan, Katarina; Lojk, Jasna; Grubic, Zoran; Pavlin, Mojca

    2015-04-01

    Transfection of primary human myoblasts offers the possibility to study mechanisms that are important for muscle regeneration and gene therapy of muscle disease. Cultured human myoblasts were selected here because muscle cells still proliferate at this developmental stage, which might have several advantages in gene therapy. Gene therapy is one of the most sought-after tools in modern medicine. Its progress is, however, limited due to the lack of suitable gene transfer techniques. To obtain better insight into the transfection potential of the presently used techniques, two non-viral transfection methods--lipofection and electroporation--were compared. The parameters that can influence transfection efficiency and cell viability were systematically approached and compared. Cultured myoblasts were transfected with the pEGFP-N1 plasmid either using Lipofectamine 2000 or with electroporation. Various combinations for the preparation of the lipoplexes and the electroporation media, and for the pulsing protocols, were tested and compared. Transfection efficiency and cell viability were inversely proportional for both approaches. The appropriate ratio of Lipofectamine and plasmid DNA provides optimal conditions for lipofection, while for electroporation, RPMI medium and a pulsing protocol using eight pulses of 2 ms at E = 0.8 kV/cm proved to be the optimal combination. The transfection efficiencies for the optimal lipofection and optimal electrotransfection protocols were similar (32 vs. 32.5%, respectively). Both of these methods are effective for transfection of primary human myoblasts; however, electroporation might be advantageous for in vivo application to skeletal muscle.

  7. The weight of nations: an estimation of adult human biomass

    Directory of Open Access Journals (Sweden)

    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.

  8. When Age and Culture Interact in an Easy and Yet Cognitively Demanding Task: Older Adults, But Not Younger Adults, Showed the Expected Cultural Differences.

    Science.gov (United States)

    Na, Jinkyung; Huang, Chih-Mao; Park, Denise C

    2017-01-01

    The interaction between age and culture can have various implications for cognition as age represents the effect of biological processes whereas culture represents the effect of sustaining experiences. Nevertheless, their interaction has rarely been examined. Thus, based on the fact that Asians are more intuitive in reasoning than Americans, we examined how this cultural difference might interact with age. Young and old participants from the US and Singapore performed a categorization task (living vs. non-living). To measure their reliance on intuition, we manipulated the typicality of targets (animate vs. inanimate). We showed that (1) RTs for inanimate organisms were slower than RTs for animate organisms (atypicality cost), (2) the cost was particularly large for older adults and (3) an age × culture interaction was observed such that cultural differences in the cost (Singaporeans > Americans) was found only among older participants. Further, we demonstrated that the age effect was associated with cognitive function and the culture effect among older adults was associated with cultural values. Finally, a moderated mediation analysis suggests that cognitive function and cultural values interact with each other in order to jointly influence one's cognition.

  9. When Age and Culture Interact in an Easy and Yet Cognitively Demanding Task: Older Adults, But Not Younger Adults, Showed the Expected Cultural Differences

    Science.gov (United States)

    Na, Jinkyung; Huang, Chih-Mao; Park, Denise C.

    2017-01-01

    The interaction between age and culture can have various implications for cognition as age represents the effect of biological processes whereas culture represents the effect of sustaining experiences. Nevertheless, their interaction has rarely been examined. Thus, based on the fact that Asians are more intuitive in reasoning than Americans, we examined how this cultural difference might interact with age. Young and old participants from the US and Singapore performed a categorization task (living vs. non-living). To measure their reliance on intuition, we manipulated the typicality of targets (animate vs. inanimate). We showed that (1) RTs for inanimate organisms were slower than RTs for animate organisms (atypicality cost), (2) the cost was particularly large for older adults and (3) an age × culture interaction was observed such that cultural differences in the cost (Singaporeans > Americans) was found only among older participants. Further, we demonstrated that the age effect was associated with cognitive function and the culture effect among older adults was associated with cultural values. Finally, a moderated mediation analysis suggests that cognitive function and cultural values interact with each other in order to jointly influence one’s cognition. PMID:28396649

  10. Important mitochondrial proteins in human omental adipose tissue show reduced expression in obesity

    Directory of Open Access Journals (Sweden)

    Peter W. Lindinger

    2015-09-01

    Full Text Available Obesity is associated with impaired mitochondrial function. This study compares mitochondrial protein expression in omental fat in obese and non-obese humans. Omental adipose tissue was obtained by surgical biopsy, adipocytes were purified and mitochondria isolated. Using anion-exchange chromatography, SDS-PAGE and mass-spectrometry, 128 proteins with potentially different abundances in patient groups were identified, 62 of the 128 proteins are mainly localized in the mitochondria. Further quantification of 12 of these 62 proteins by immune dot blot analysis revealed four proteins citrate synthase, HADHA, LETM1 and mitofilin being inversely associated with BMI, and mitofilin being inversely correlated with gender.

  11. Important mitochondrial proteins in human omental adipose tissue show reduced expression in obesity.

    Science.gov (United States)

    Lindinger, Peter W; Christe, Martine; Eberle, Alex N; Kern, Beatrice; Peterli, Ralph; Peters, Thomas; Jayawardene, Kamburapola J I; Fearnley, Ian M; Walker, John E

    2015-09-01

    Obesity is associated with impaired mitochondrial function. This study compares mitochondrial protein expression in omental fat in obese and non-obese humans. Omental adipose tissue was obtained by surgical biopsy, adipocytes were purified and mitochondria isolated. Using anion-exchange chromatography, SDS-PAGE and mass-spectrometry, 128 proteins with potentially different abundances in patient groups were identified, 62 of the 128 proteins are mainly localized in the mitochondria. Further quantification of 12 of these 62 proteins by immune dot blot analysis revealed four proteins citrate synthase, HADHA, LETM1 and mitofilin being inversely associated with BMI, and mitofilin being inversely correlated with gender.

  12. Human area MT+ shows load-dependent activation during working memory maintenance with continuously morphing stimulation.

    Science.gov (United States)

    Galashan, Daniela; Fehr, Thorsten; Kreiter, Andreas K; Herrmann, Manfred

    2014-07-11

    Initially, human area MT+ was considered a visual area solely processing motion information but further research has shown that it is also involved in various different cognitive operations, such as working memory tasks requiring motion-related information to be maintained or cognitive tasks with implied or expected motion.In the present fMRI study in humans, we focused on MT+ modulation during working memory maintenance using a dynamic shape-tracking working memory task with no motion-related working memory content. Working memory load was systematically varied using complex and simple stimulus material and parametrically increasing retention periods. Activation patterns for the difference between retention of complex and simple memorized stimuli were examined in order to preclude that the reported effects are caused by differences in retrieval. Conjunction analysis over all delay durations for the maintenance of complex versus simple stimuli demonstrated a wide-spread activation pattern. Percent signal change (PSC) in area MT+ revealed a pattern with higher values for the maintenance of complex shapes compared to the retention of a simple circle and with higher values for increasing delay durations. The present data extend previous knowledge by demonstrating that visual area MT+ presents a brain activity pattern usually found in brain regions that are actively involved in working memory maintenance.

  13. 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.

  14. Abstinent adult daily smokers show reduced anticipatory but elevated saccade-related brain responses during a rewarded antisaccade task.

    Science.gov (United States)

    Geier, Charles F; Sweitzer, Maggie M; Denlinger, Rachel; Sparacino, Gina; Donny, Eric C

    2014-08-30

    Chronic smoking may result in reduced sensitivity to non-drug rewards (e.g., money), a phenomenon particularly salient during abstinence. During a quit attempt, this effect may contribute to biased decision-making (smoking>alternative reinforcers) and relapse. Although relevant for quitting, characterization of reduced reward function in abstinent smokers remains limited. Moreover, how attenuated reward function affects other brain systems supporting decision-making has not been established. Here, we use a rewarded antisaccade (rAS) task to characterize non-drug reward processing and its influence on inhibitory control, key elements underlying decision-making, in abstinent smokers vs. non-smokers. Abstinent (12-hours) adult daily smokers (N=23) and non-smokers (N=11) underwent fMRI while performing the rAS. Behavioral performances improved on reward vs. neutral trials. Smokers showed attenuated activation in ventral striatum during the reward cue and in superior precentral sulcus and posterior parietal cortex during response preparation, but greater responses during the saccade response in posterior cingulate and parietal cortices. Smokers' attenuated anticipatory responses suggest reduced motivation from monetary reward, while heightened activation during the saccade response suggests that additional circuitry may be engaged later to enhance inhibitory task performance. Overall, this preliminary study highlights group differences in decision-making components and the utility of the rAS to characterize these effects. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. 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.

  16. 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...

  17. 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…

  18. Shyer and larger bird species show more reduced fear of humans when living in urban environments.

    Science.gov (United States)

    delBarco-Trillo, Javier

    2018-04-01

    As the natural habitats of many species are degraded or disappear, there is scope for these species to be established in urban habitats. To ease the establishment and maintenance of urban populations of more species we need to better understand what degree of phenotypical change to expect as different species transition into urban environments. During the first stages of urban colonization, behavioural changes such as an increase in boldness are particularly important. A consistent response in urban populations is to decrease the distance at which individuals flee from an approaching human (flight initiation distance, or FID). Performing a phylogenetic generalized least-squares (PGLS) analysis on 130 avian species, I found that the largest changes in FID between rural and urban populations occur in species that are larger-bodied and naturally shy (higher rural FID), two phenotypic traits that are not normally associated with urban colonizers. More unlikely species may thus be able to colonize urban environments, especially if we design cities in ways that promote such urban colonizations. © 2018 The Author(s).

  19. Three New Escherichia coli Phages from the Human Gut Show Promising Potential for Phage Therapy.

    Directory of Open Access Journals (Sweden)

    Marion Dalmasso

    Full Text Available With the emergence of multi-drug resistant bacteria the use of bacteriophages (phages is gaining renewed interest as promising anti-microbial agents. The aim of this study was to isolate and characterize phages from human fecal samples. Three new coliphages, ɸAPCEc01, ɸAPCEc02 and ɸAPCEc03, were isolated. Their phenotypic and genomic characteristics, and lytic activity against biofilm, and in combination with ciprofloxacin, were investigated. All three phages reduced the growth of E. coli strain DPC6051 at multiplicity of infection (MOI between 10-3 and 105. A cocktail of all three phages completely inhibited the growth of E. coli. The phage cocktail also reduced biofilm formation and prevented the emergence of phage-resistant mutants which occurred with single phage. When combined with ciprofloxacin, phage alone or in cocktail inhibited the growth of E. coli and prevented the emergence of resistant mutants. These three new phages are promising biocontrol agents for E. coli infections.

  20. Peanut sensitization pattern in Norwegian children and adults with specific IgE to peanut show age related differences.

    Science.gov (United States)

    Namork, Ellen; Stensby, Berit A

    2015-01-01

    Peanuts contain potent food allergens and the prevalence of allergy is reported to increase, especially in children. Since peanut sensitization may differ between different geographical regions, we wanted to investigate the sensitization pattern to the individual peanut allergens in a Norwegian population. Cases reported to the Norwegian Food Allergy Register with sera positive to peanut extract were analyzed for specific IgE (sIgE) to the recombinant peanut allergens Ara h 1, Ara h 2, Ara h 3, Ara h 8 and Ara h 9 and to birch pollen extract. Serum samples negative to the above allergens were analyzed for sIgE to Ara h 6, and sIgE to Pru p 3 in peach were analyzed in sera positive to the cross-reactive allergen Ara h 9. Highest frequency of sIgE to Ara h 2, often co-sensitized to Ara h 1 and 3, were found in the small children up to 6 years of age. From the age of 6 years, sensitization to Ara h 8 was predominant. The sIgE levels to the storage proteins Ara h 1, 2 and 3 were strongly correlated, as was the sIgE levels to Ara h 8 and birch pollen extract. A low sensitization rate of sIgE to Ara h 9 in young adults was observed, which sIgE levels were very strongly correlated to Pru p 3. The sensitization to peanut allergens in a Norwegian population shows a clear age dependent pattern. The results add to the previously published research on the sensitization patterns of peanut sensitized patients in different geographical areas.

  1. Ensemble refinement shows conformational flexibility in crystal structures of human complement factor D

    International Nuclear Information System (INIS)

    Forneris, Federico; Burnley, B. Tom; Gros, Piet

    2014-01-01

    Ensemble-refinement analysis of native and mutant factor D (FD) crystal structures indicates a dynamical transition in FD from a self-inhibited inactive conformation to a substrate-bound active conformation that is reminiscent of the allostery in thrombin. Comparison with previously observed dynamics in thrombin using NMR data supports the crystallographic ensembles. Human factor D (FD) is a self-inhibited thrombin-like serine proteinase that is critical for amplification of the complement immune response. FD is activated by its substrate through interactions outside the active site. The substrate-binding, or ‘exosite’, region displays a well defined and rigid conformation in FD. In contrast, remarkable flexibility is observed in thrombin and related proteinases, in which Na + and ligand binding is implied in allosteric regulation of enzymatic activity through protein dynamics. Here, ensemble refinement (ER) of FD and thrombin crystal structures is used to evaluate structure and dynamics simultaneously. A comparison with previously published NMR data for thrombin supports the ER analysis. The R202A FD variant has enhanced activity towards artificial peptides and simultaneously displays active and inactive conformations of the active site. ER revealed pronounced disorder in the exosite loops for this FD variant, reminiscent of thrombin in the absence of the stabilizing Na + ion. These data indicate that FD exhibits conformational dynamics like thrombin, but unlike in thrombin a mechanism has evolved in FD that locks the unbound native state into an ordered inactive conformation via the self-inhibitory loop. Thus, ensemble refinement of X-ray crystal structures may represent an approach alternative to spectroscopy to explore protein dynamics in atomic detail

  2. Human decellularized bone scaffolds from aged donors show improved osteoinductive capacity compared to young donor bone.

    Directory of Open Access Journals (Sweden)

    Christopher A Smith

    Full Text Available To improve the safe use of allograft bone, decellularization techniques may be utilized to produce acellular scaffolds. Such scaffolds should retain their innate biological and biomechanical capacity and support mesenchymal stem cell (MSC osteogenic differentiation. However, as allograft bone is derived from a wide age-range, this study aimed to determine whether donor age impacts on the ability an osteoinductive, acellular scaffold produced from human bone to promote the osteogenic differentiation of bone marrow MSCs (BM-MSC. BM-MSCs from young and old donors were seeded on acellular bone cubes from young and old donors undergoing osteoarthritis related hip surgery. All combinations resulted in increased osteogenic gene expression, and alkaline phosphatase (ALP enzyme activity, however BM-MSCs cultured on old donor bone displayed the largest increases. BM-MSCs cultured in old donor bone conditioned media also displayed higher osteogenic gene expression and ALP activity than those exposed to young donor bone conditioned media. ELISA and Luminex analysis of conditioned media demonstrated similar levels of bioactive factors between age groups; however, IGF binding protein 1 (IGFBP1 concentration was significantly higher in young donor samples. Additionally, structural analysis of old donor bone indicated an increased porosity compared to young donor bone. These results demonstrate the ability of a decellularized scaffold produced from young and old donors to support osteogenic differentiation of cells from young and old donors. Significantly, the older donor bone produced greater osteogenic differentiation which may be related to reduced IGFBP1 bioavailability and increased porosity, potentially explaining the excellent clinical results seen with the use of allograft from aged donors.

  3. Optical and Biometric Characteristics of Anisomyopia in Human Adults

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  5. 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.

  6. Show me a woman! : narratives of gender and violence in human rights law and processes of transitional justice

    NARCIS (Netherlands)

    Mibenge, C.S.|info:eu-repo/dai/nl/304834165

    2010-01-01

    Show me a woman who wasn’t raped!’ These words, thrown down like a gauntlet by a genocide survivor disrupted the narrative of transitional justice as the panacea to redressing gross human rights violations committed against civilian women. The challenge to ‘show me a woman’ is made from a local

  7. Saccharomyces cerevisiae show low levels of traversal across human endothelial barrier in vitro [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Roberto Pérez-Torrado

    2017-09-01

    Full Text Available Background:  Saccharomyces cerevisiae is generally considered safe, and is involved in the production of many types of foods and dietary supplements. However, some isolates, which are genetically related to strains used in brewing and baking, have shown virulent traits, being able to produce infections in humans, mainly in immunodeficient patients. This can lead to systemic infections in humans. Methods: In this work, we studied S. cerevisiae isolates in an in vitro human endothelial barrier model, comparing their behaviour with that of several strains of the related pathogens Candida glabrata and Candida albicans. Results: The results showed that this food related yeast is able to cross the endothelial barrier in vitro. However, in contrast to C. glabrata and C. albicans, S. cerevisiae showed very low levels of traversal. Conclusions: We conclude that using an in vitro human endothelial barrier model with S. cerevisiae can be useful to evaluate the safety of S. cerevisiae strains isolated from foods.

  8. Younger Adults Show Long-Term Effects of Cognitive Training on Broad Cognitive Abilities over 2 Years

    Science.gov (United States)

    Schmiedek, Florian; Lövdén, Martin; Lindenberger, Ulman

    2014-01-01

    In the COGITO study (Schmiedek, Lövdén, & Lindenberger, 2010), 101 younger adults practiced 12 tests of perceptual speed, working memory, and episodic memory for over 100 daily 1-hr sessions. The intervention resulted in positive transfer to broad cognitive abilities, including reasoning and episodic memory. Here, we examine whether these…

  9. High Density Sphere Culture of Adult Cardiac Cells Increases the Levels of Cardiac and Progenitor Markers and Shows Signs of Vasculogenesis

    Directory of Open Access Journals (Sweden)

    Kristina Vukusic

    2013-01-01

    Full Text Available 3D environment and high cell density play an important role in restoring and supporting the phenotypes of cells represented in cardiac tissues. The aim of this study was therefore to investigate the suitability of high density sphere (HDS cultures for studies of cardiomyocyte-, endothelial-, and stem-cell biology. Primary adult cardiac cells from nine human biopsies were cultured using different media for up to 9 weeks. The possibilities to favor a certain cell phenotype and induce production of extra cellular matrix (ECM were studied by histology, immunohistochemistry, and quantitative real-time PCR. Defined media gave significant increase in both cardiac- and progenitor-specific markers and also an intraluminal position of endothelial cells over time. Cardiac media showed indication of differentiation and maturity of HDS considering the ECM production and activities within NOTCH regulation but no additional cardiac differentiation. Endothelial media gave no positive effects on endothelial phenotype but increased proliferation without fibroblast overgrowth. In addition, indications for early vasculogenesis were found. It was also possible to affect the Wnt signaling in HDS by addition of a glycogen synthase kinase 3 (GSK3 inhibitor. In conclusion, these findings show the suitability of HDS as in vitro model for studies of cardiomyocyte-, endothelial-, and stem-cell biology.

  10. 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...

  11. 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 ...

  12. 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.

  13. I Show You How I Like You: Emotional Human-Robot Interaction through Facial Expression and Tactile Stimulation

    DEFF Research Database (Denmark)

    Fredslund, Jakob; Cañamero, Lola D.

    2001-01-01

    We report work on a LEGO robot capable of displaying several emo- tional expressions in response to physical contact. Our motivation has been to explore believable emotional exchanges to achieve plausible interaction with a simple robot. We have worked toward this goal in two ways. First......, acknowledging the importance of physical manipulation in children's inter- actions, interaction with the robot is through tactile stimulation; the various kinds of stimulation that can elicit the robot's emotions are grounded in a model of emotion activation based on different stimulation patterns. Sec- ond......, emotional states need to be clearly conveyed. We have drawn inspira- tion from theories of human basic emotions with associated universal facial expressions, which we have implemented in a caricaturized face. We have conducted experiments on both children and adults to assess the recogniz- ability...

  14. Oogenesis in cultures derived from adult human ovaries

    Directory of Open Access Journals (Sweden)

    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.

  15. Individual Diet Modeling Shows How to Balance the Diet of French Adults with or without Excessive Free Sugar Intakes.

    Science.gov (United States)

    Lluch, Anne; Maillot, Matthieu; Gazan, Rozenn; Vieux, Florent; Delaere, Fabien; Vaudaine, Sarah; Darmon, Nicole

    2017-02-20

    Dietary changes needed to achieve nutritional adequacy for 33 nutrients were determined for 1719 adults from a representative French national dietary survey. For each individual, an iso-energy nutritionally adequate diet was generated using diet modeling, staying as close as possible to the observed diet. The French food composition table was completed with free sugar (FS) content. Results were analyzed separately for individuals with FS intakes in their observed diets ≤10% or >10% of their energy intake (named below FS-ACCEPTABLE and FS-EXCESS, respectively). The FS-EXCESS group represented 41% of the total population (average energy intake of 14.2% from FS). Compared with FS-ACCEPTABLE individuals, FS-EXCESS individuals had diets of lower nutritional quality and consumed more energy (2192 vs. 2123 kcal/day), particularly during snacking occasions (258 vs. 131 kcal/day) (all p -values diets were significant increases in fresh fruits, starchy foods, water, hot beverages and plain yogurts; and significant decreases in mixed dishes/sandwiches, meat/eggs/fish and cheese. For FS-EXCESS individuals only, the optimization process significantly increased vegetables and significantly decreased sugar-sweetened beverages, sweet products and fruit juices. The diets of French adults with excessive intakes of FS are of lower nutritional quality, but can be optimized via specific dietary changes.

  16. In vitro proliferation of adult human beta-cells.

    Directory of Open Access Journals (Sweden)

    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.

  17. Using films and television shows with a medical theme as a medium to accelerate the spread of medical humanities.

    Science.gov (United States)

    Chen, Wenting; Qian, Haihong

    2017-05-23

    People have more visual experiences than ever before, and the same is true for situations in medicine. More mature films and television shows with a medical theme have been available over the past 20 years. In mainland China, the TV series "Angel Heart" has generated a wave of universal concern since it truly depicts the work of health care workers and it reflects the sharp distinction between doctors and patients to a certain extent. Riding this wave, many medical documentaries like The Human World have also been launched in China and have garnered sizable audiences. Such films and television shows with a medical theme strive to depict the lives of ordinary people. When watching these medical documentaries, audiences are able to better comprehend the work of health care workers in light of their life experiences and feelings towards current society. Audiences can gain a profound understanding of the medical humanities through films and television shows with a medical theme. We look forward to more such films and television shows with a medical theme that depict "hospitals-the realest place" on camera. Films and television shows with a medical theme can serve as a storytelling medium to accelerate the spread of medical humanities and to promote harmony among doctors, patients, and the public.

  18. Biologic and Conventional Systemic Therapies Show Similar Safety and Efficacy in Elderly and Adult Patients With Moderate to Severe Psoriasis.

    Science.gov (United States)

    Garber, Caren; Plotnikova, Natalia; Au, Shiu-chung; Sorensen, Eric P; Gottlieb, Alice

    2015-08-01

    Despite the aging population, few studies have documented the treatment of geriatric psoriasis. The purpose of this study is to compare the efficacy, safety, and prescribing patterns of biologics and conventional systemic medications in elderly versus adult psoriasis. All patient visits coded for psoriasis or psoriatic arthritis (ICD-9 696.1 or 696.0) at the Tufts Medical Center General Dermatology Clinic from January 1, 2008, to March 1, 2015 were included in this retrospective cohort study. The outcome measure used was the validated simple-measure for assessing psoriasis activity (S-MAPA), the product of the physician's global assessment and the body surface area. 194 patients who underwent 278 treatment courses were included in the study. 48 patients were included in the elderly cohort (≥ 65 years old) and 146 in the adult cohort (18-64 years old). There was no significant difference in S-MAPA improvement at 12 weeks between the two cohorts when treated with biologics (42.92% improvement in adults, 48.77% in elderly; P=0.498) or conventional systemics (43.96% and 51.82%, respectively; P=0.448). Within the elderly cohort, there was no significant difference in efficacy of biologics versus conventional systemics at any time point. Topical prescription rates were significantly higher in the elderly cohort ( P=0.004) while biologic prescription rates were significantly lower ( P=0.014) despite the same baseline S-MAPA in both age groups. For both biologics and conventional systemics, there was no statistically significant intergroup difference in the rate of adverse events ( P=0.322 for biologics; P=0.581 for conventional systemics) or infection ( P=0.753 for biologics; P=0.828 for conventional systemics). Within the elderly cohort, there was a higher rate of adverse events with conventional systemic treatment than with biologic treatment ( P=0.033). This study provides preliminary evidence to suggest that biologic and conventional systemic therapies are similarly

  19. Pulmonary Arterial Hypertension in Adults: Novel Drugs and Catheter Ablation Techniques Show Promise? Systematic Review on Pharmacotherapy and Interventional Strategies

    Directory of Open Access Journals (Sweden)

    Salvatore Rosanio

    2014-01-01

    Full Text Available This systematic review aims to provide an update on pharmacological and interventional strategies for the treatment of pulmonary arterial hypertension in adults. Currently US Food and Drug Administration approved drugs including prostanoids, endothelin-receptor antagonists, phosphodiesterase type-5 inhibitors, and soluble guanylate-cyclase stimulators. These agents have transformed the prognosis for pulmonary arterial hypertension patients from symptomatic improvements in exercise tolerance ten years ago to delayed disease progression today. On the other hand, percutaneous balloon atrioseptostomy by using radiofrequency perforation, cutting balloon dilatation, or insertion of butterfly stents and pulmonary artery catheter-based denervation, both associated with very low rate of major complications and death, should be considered in combination with specific drugs at an earlier stage rather than late in the progression of pulmonary arterial hypertension and before the occurrence of overt right-sided heart failure.

  20. Survey results show that adults are willing to pay higher insurance premiums for generous coverage of specialty drugs.

    Science.gov (United States)

    Romley, John A; Sanchez, Yuri; Penrod, John R; Goldman, Dana P

    2012-04-01

    Generous coverage of specialty drugs for cancer and other diseases may be valuable not only for sick patients currently using these drugs, but also for healthy people who recognize the potential need for them in the future. This study estimated how healthy people value insurance coverage of specialty drugs, defined as high-cost drugs that treat cancer and other serious health conditions like multiple sclerosis, by quantifying willingness to pay via a survey. US adults were estimated to be willing to pay an extra $12.94 on average in insurance premiums per month for generous specialty-drug coverage--in effect, $2.58 for every dollar in out-of-pocket costs that they would expect to pay with a less generous insurance plan. Given the value that people assign to generous coverage of specialty drugs, having high cost sharing on these drugs seemingly runs contrary to what people value in their health insurance.

  1. Expression analysis of genes associated with human osteosarcoma tumors shows correlation of RUNX2 overexpression with poor response to chemotherapy

    International Nuclear Information System (INIS)

    Sadikovic, Bekim; Thorner, Paul; Chilton-MacNeill, Susan; Martin, Jeff W; Cervigne, Nilva K; Squire, Jeremy; Zielenska, Maria

    2010-01-01

    Human osteosarcoma is the most common pediatric bone tumor. There is limited understanding of the molecular mechanisms underlying osteosarcoma oncogenesis, and a lack of good diagnostic as well as prognostic clinical markers for this disease. Recent discoveries have highlighted a potential role of a number of genes including: RECQL4, DOCK5, SPP1, RUNX2, RB1, CDKN1A, P53, IBSP, LSAMP, MYC, TNFRSF1B, BMP2, HISTH2BE, FOS, CCNB1, and CDC5L. Our objective was to assess relative expression levels of these 16 genes as potential biomarkers of osteosarcoma oncogenesis and chemotherapy response in human tumors. We performed quantitative expression analysis in a panel of 22 human osteosarcoma tumors with differential response to chemotherapy, and 5 normal human osteoblasts. RECQL4, SPP1, RUNX2, and IBSP were significantly overexpressed, and DOCK5, CDKN1A, RB1, P53, and LSAMP showed significant loss of expression relative to normal osteoblasts. In addition to being overexpressed in osteosarcoma tumor samples relative to normal osteoblasts, RUNX2 was the only gene of the 16 to show significant overexpression in tumors that had a poor response to chemotherapy relative to good responders. These data underscore the loss of tumor suppressive pathways and activation of specific oncogenic mechanisms associated with osteosarcoma oncogenesis, while drawing attention to the role of RUNX2 expression as a potential biomarker of chemotherapy failure in osteosarcoma

  2. Neurons in the white matter of the adult human neocortex

    Directory of Open Access Journals (Sweden)

    M Luisa Suarez-Sola

    2009-06-01

    Full Text Available The white matter (WM of the adult human neocortex contains the so-called “interstitial neurons”. They are most numerous in the superficial WM underlying the cortical gyri, and decrease in density toward the deep WM. They are morphologically heterogeneous. A subgroup of interstitial neurons display pyramidal-cell like morphologies, characterized by a polarized dendritic tree with a dominant apical dendrite, and covered with a variable number of dendritic spines. In addition, a large contingent of interstitial neurons can be classified as interneurons based on their neurochemical profile as well as on morphological criteria. WM- interneurons have multipolar or bipolar shapes and express GABA and a variety of other neuronal markers, such as calbindin and calretinin, the extracellular matrix protein reelin, or neuropeptide Y, somatostatin, and nitric oxide synthase. The heterogeneity of interstitial neurons may be relevant for the pathogenesis of Alzheimer disease and schizophrenia. Interstitial neurons are most prominent in human brain, and only rudimentary in the brain of non-primate mammals. These evolutionary differences have precluded adequate experimental work on this cell population, which is usually considered as a relict of the subplate, a transient compartment proper of development and without a known function in the adult brain. The primate-specific prominence of the subplate in late fetal stages points to an important role in the establishment of interstitial neurons. Neurons in the adult WM may be actively involved in coordinating inter-areal connectivity and regulation of blood flow. Further studies in primates will be needed to elucidate the developmental history, adult components and activities of this large neuronal system.

  3. Transgenic rats overexpressing the human MrgX3 gene show cataracts and an abnormal skin phenotype

    International Nuclear Information System (INIS)

    Kaisho, Yoshihiko; Watanabe, Takuya; Nakata, Mitsugu; Yano, Takashi; Yasuhara, Yoshitaka; Shimakawa, Kozo; Mori, Ikuo; Sakura, Yasufumi; Terao, Yasuko; Matsui, Hideki; Taketomi, Shigehisa

    2005-01-01

    The human MrgX3 gene, belonging to the mrgs/SNSRs (mass related genes/sensory neuron specific receptors) family, was overexpressed in transgenic rats using the actin promoter. Two animal lines showed cataracts with liquification/degeneration and swelling of the lens fiber cells. The transient epidermal desquamation was observed in line with higher gene expression. Histopathology of the transgenic rats showed acanthosis and focal parakeratosis. In the epidermis, there was an increase in cellular keratin 14, keratin 10, and loricrin, as well as PGP 9.5 in innervating nerve fibers. These phenotypes accompanied an increase in the number of proliferating cells. These results suggest that overexpression of the human MrgX3 gene causes a disturbance of the normal cell-differentiation process

  4. Periodontitis and oral human papillomavirus infection among Hispanic adults

    Directory of Open Access Journals (Sweden)

    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

  5. Endothelial Protein C–Targeting Liposomes Show Enhanced Uptake and Improved Therapeutic Efficacy in Human Retinal Endothelial Cells

    DEFF Research Database (Denmark)

    Arta, Anthoula; Eriksen, Anne Z.; Melander, Fredrik

    2018-01-01

    PURPOSE. To determine whether human retinal endothelial cells (HRECs) express the endothelial cell protein C receptor (EPCR) and to realize its potential as a targeting moiety by developing novel single and dual corticosteroid–loaded functionalized liposomes that exhibit both enhanced uptake by H...... of cell tube formations in contrast to nontargeting liposomes. CONCLUSIONS. We show that HRECs express EPCR and this receptor could be a promising nanomedicine target in ocular diseases where the endothelial barrier of the retina is compromised....

  6. 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.

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

    Science.gov (United States)

    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

  8. 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....

  9. Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Nef Proteins Show Distinct Patterns and Mechanisms of Src Kinase Activation

    Science.gov (United States)

    Greenway, Alison L.; Dutartre, Hélène; Allen, Kelly; McPhee, Dale A.; Olive, Daniel; Collette, Yves

    1999-01-01

    The nef gene from human and simian immunodeficiency viruses (HIV and SIV) regulates cell function and viral replication, possibly through binding of the nef product to cellular proteins, including Src family tyrosine kinases. We show here that the Nef protein encoded by SIVmac239 interacts with and also activates the human Src kinases Lck and Hck. This is in direct contrast to the inhibitory effect of HIV type 1 (HIV-1) Nef on Lck catalytic activity. Unexpectedly, however, the interaction of SIV Nef with human Lck or Hck is not mediated via its consensus proline motif, which is known to mediate HIV-1 Nef binding to Src homology 3 (SH3) domains, and various experimental analyses failed to show significant interaction of SIV Nef with the SH3 domain of either kinase. Instead, SIV Nef can bind Lck and Hck SH2 domains, and its N-terminal 50 amino acid residues are sufficient for Src kinase binding and activation. Our results provide evidence for multiple mechanisms by which Nef binds to and regulates Src kinases. PMID:10364375

  10. Human microRNA oncogenes and tumor suppressors show significantly different biological patterns: from functions to targets.

    Directory of Open Access Journals (Sweden)

    Dong Wang

    Full Text Available MicroRNAs (miRNAs are small noncoding RNAs which play essential roles in many important biological processes. Therefore, their dysfunction is associated with a variety of human diseases, including cancer. Increasing evidence shows that miRNAs can act as oncogenes or tumor suppressors, and although there is great interest in research into these cancer-associated miRNAs, little is known about them. In this study, we performed a comprehensive analysis of putative human miRNA oncogenes and tumor suppressors. We found that miRNA oncogenes and tumor suppressors clearly show different patterns in function, evolutionary rate, expression, chromosome distribution, molecule size, free energy, transcription factors, and targets. For example, miRNA oncogenes are located mainly in the amplified regions in human cancers, whereas miRNA tumor suppressors are located mainly in the deleted regions. miRNA oncogenes tend to cleave target mRNAs more frequently than miRNA tumor suppressors. These results indicate that these two types of cancer-associated miRNAs play different roles in cancer formation and development. Moreover, the patterns identified here can discriminate novel miRNA oncogenes and tumor suppressors with a high degree of accuracy. This study represents the first large-scale bioinformatic analysis of human miRNA oncogenes and tumor suppressors. Our findings provide help for not only understanding of miRNAs in cancer but also for the specific identification of novel miRNAs as miRNA oncogenes and tumor suppressors. In addition, the data presented in this study will be valuable for the study of both miRNAs and cancer.

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

    DEFF Research Database (Denmark)

    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...

  12. Dual RNAseq shows the human mucosal immunity protein, MUC13, is a hallmark of Plasmodium exoerythrocytic infection

    KAUST Repository

    LaMonte, Gregory; Orjuela-Sanchez, Pamela; Wang, Lawrence; Li, Shangzhong; Swann, Justine; Cowell, Annie; Zou, Bing Yu; Abdel- Haleem Mohamed, Alyaa; Villa-Galarce, Zaira; Moreno, Marta; Tong-Rios, Carlos; Vinetz, Joseph; Lewis, Nathan; Winzeler, Elizabeth A

    2017-01-01

    The exoerythrocytic stage of Plasmodium malaria infection is a critical window for prophylactic intervention. Using a genome-wide dual RNA sequencing of flow-sorted infected and uninfected hepatoma cells we identify the human mucosal immunity gene, Mucin13 (MUC13), as strongly upregulated during Plasmodium exoerythrocytic hepatic-stage infection. We confirm that MUC13 expression is upregulated in hepatoma cell lines and primary hepatocytes. In immunofluorescence assays, host MUC13 protein expression distinguishes infected cells from adjacent uninfected cells and shows similar colocalization with parasite biomarkers such as UIS4 and HSP70. We further show that localization patterns are species independent, distinguishing both P. berghei and P. vivax infected cells, and that MUC13 can be used to identify compounds that inhibit parasite replication in hepatocytes across all Human-infecting Plasmodium species. This data presents a novel interface of host-parasite interactions in Plasmodium, in that a component of host mucosal immunity is reprogrammed to assist the progression of infection.

  13. Dual RNAseq shows the human mucosal immunity protein, MUC13, is a hallmark of Plasmodium exoerythrocytic infection

    KAUST Repository

    LaMonte, Gregory

    2017-10-03

    The exoerythrocytic stage of Plasmodium malaria infection is a critical window for prophylactic intervention. Using a genome-wide dual RNA sequencing of flow-sorted infected and uninfected hepatoma cells we identify the human mucosal immunity gene, Mucin13 (MUC13), as strongly upregulated during Plasmodium exoerythrocytic hepatic-stage infection. We confirm that MUC13 expression is upregulated in hepatoma cell lines and primary hepatocytes. In immunofluorescence assays, host MUC13 protein expression distinguishes infected cells from adjacent uninfected cells and shows similar colocalization with parasite biomarkers such as UIS4 and HSP70. We further show that localization patterns are species independent, distinguishing both P. berghei and P. vivax infected cells, and that MUC13 can be used to identify compounds that inhibit parasite replication in hepatocytes across all Human-infecting Plasmodium species. This data presents a novel interface of host-parasite interactions in Plasmodium, in that a component of host mucosal immunity is reprogrammed to assist the progression of infection.

  14. Foodstuff analyses show that seafood and water are major perfluoroalkyl acids (PFAAs) sources to humans in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Heo, Jin-Ju; Lee, Ji-Woo [Department of Civil and Environmental Engineering, Pusan National University, Busan, 609-735 (Korea, Republic of); Kim, Seung-Kyu [Department of Marine Science, College of Natural Sciences, Incheon National University, Incheon, 406-772 (Korea, Republic of); Oh, Jeong-Eun, E-mail: jeoh@pusan.ac.kr [Department of Civil and Environmental Engineering, Pusan National University, Busan, 609-735 (Korea, Republic of)

    2014-08-30

    Graphical abstract: - Highlights: • 16 PFAAs in 397 samples of 66 food types and 34 tap water samples were analyzed. • Dietary exposure to PFAAs was estimated by using the PFAAs measured concentrations. • The major contributors of PFAAs dietary exposure were confirmed. - Abstract: We measured concentrations of PFAAs in 397 foods, of 66 types, in Korea, and determined the daily human dietary PFAAs intake and the contribution of each foodstuff to that intake. The PFAAs concentration in the 66 different food types ranged from below the detection limit to 48.3 ng/g. Perfluorooctane sulfonate (PFOS) and long-chain perfluorocarboxylic acids (PFCAs) were the dominant PFAAs in fish, shellfish, and processed foods, while perfluorooctanoic acid (PFOA) and short-chain PFCAs dominated dairy foodstuffs and beverages. The Korean adult dietary intake ranges, estimated for a range of scenarios, were 0.60–3.03 and 0.17–1.68 ng kg{sup −1} bw d{sup −1} for PFOS and PFOA, respectively, which were lower than the total daily intake limits suggested by European Food Safety Authority (PFOS: 150 ng kg{sup −1} bw d{sup −1}; PFOA: 1500 ng kg{sup −1} bw d{sup −1}). The major contributors to PFAAs dietary exposure varied with subject age and PFAAs. For example, fish was a major contributor of PFOS but dairy foods were major contributors of PFOA. However, tap water was a major contributor to PFOA intake when it was the main source of drinking water (rather than bottled water)

  15. Foodstuff analyses show that seafood and water are major perfluoroalkyl acids (PFAAs) sources to humans in Korea

    International Nuclear Information System (INIS)

    Heo, Jin-Ju; Lee, Ji-Woo; Kim, Seung-Kyu; Oh, Jeong-Eun

    2014-01-01

    Graphical abstract: - Highlights: • 16 PFAAs in 397 samples of 66 food types and 34 tap water samples were analyzed. • Dietary exposure to PFAAs was estimated by using the PFAAs measured concentrations. • The major contributors of PFAAs dietary exposure were confirmed. - Abstract: We measured concentrations of PFAAs in 397 foods, of 66 types, in Korea, and determined the daily human dietary PFAAs intake and the contribution of each foodstuff to that intake. The PFAAs concentration in the 66 different food types ranged from below the detection limit to 48.3 ng/g. Perfluorooctane sulfonate (PFOS) and long-chain perfluorocarboxylic acids (PFCAs) were the dominant PFAAs in fish, shellfish, and processed foods, while perfluorooctanoic acid (PFOA) and short-chain PFCAs dominated dairy foodstuffs and beverages. The Korean adult dietary intake ranges, estimated for a range of scenarios, were 0.60–3.03 and 0.17–1.68 ng kg −1 bw d −1 for PFOS and PFOA, respectively, which were lower than the total daily intake limits suggested by European Food Safety Authority (PFOS: 150 ng kg −1 bw d −1 ; PFOA: 1500 ng kg −1 bw d −1 ). The major contributors to PFAAs dietary exposure varied with subject age and PFAAs. For example, fish was a major contributor of PFOS but dairy foods were major contributors of PFOA. However, tap water was a major contributor to PFOA intake when it was the main source of drinking water (rather than bottled water)

  16. A Content Analysis of How Sexual Behavior and Reproductive Health are Being Portrayed on Primetime Television Shows Being Watched by Teens and Young Adults.

    Science.gov (United States)

    Kinsler, Janni J; Glik, Deborah; de Castro Buffington, Sandra; Malan, Hannah; Nadjat-Haiem, Carsten; Wainwright, Nicole; Papp-Green, Melissa

    2018-02-01

    Television is a leading source of sexual education for teens and young adults, thus it is important to understand how sexual behavior and reproductive health are portrayed in popular primetime programming. This study is a media content analysis of the 19 top-rated scripted English-language primetime television shows aired between January 1, 2015 and May 31, 2015, and viewed by American youth audiences 12-24 years of age. The purpose of this study is to assess how sex/sexuality and reproductive health are being portrayed in a popular medium that reaches many adolescent and young adult audiences. Themes used for this analysis include youth pregnancy/parenting, mentoring/guidance of youth regarding sexual behavior, sex/sexuality, body image/identity, sexual violence/abuse/harassment, gender identity/sexual orientation, and reproductive health. Themes have been classified in one of the following six categories: visual cues, brief mentions, dialogue, minor storylines, major storylines, and multi-episode storylines. Our findings indicate that narratives providing educational information regarding the risks and consequences of sexual behavior were missing from the television shows we analyzed and that storylines promoting low risk sexual behavior were rare. Sexual violence and abuse, casual sex among adults, lack of contraception use, or no portrayal of consequences of risky behaviors were common. Compared to prior research, we found an emergent theme normalizing non-heterosexual gender identity and sexual orientation. Our findings have important implications as exposure to popular media shapes the perceptions and behaviors of teens and young adults. This study has the potential to shed light on the need to create stories and narratives in television shows watched by American teens and young adults with educational messages regarding the risks and consequences of sexual behavior.

  17. Collagen VII deficient mice show morphologic and histologic corneal changes that phenotypically mimic human dystrophic epidermolysis bullosa of the eye.

    Science.gov (United States)

    Chen, Vicki M; Shelke, Rajani; Nyström, Alexander; Laver, Nora; Sampson, James F; Zhiyi, Cao; Bhat, Najma; Panjwani, Noorjahan

    2018-06-16

    Absence of collagen VII causes blistering of the skin, eyes and many other tissues. This disease is termed dystrophic epidermolysis bullosa (DEB). Corneal fibrosis occurs in up to 41% and vision loss in up to 64% of patients. Standard treatments are supportive and there is no cure. The immune-histologic and morphologic changes in the corneas of the mouse model for this disease have not been described in the literature. Our purpose is to characterize the eyes of these mice to determine if this is an appropriate model for study of human therapeutics. Western blot analysis (WB) and immunohistochemistry (IHC) were performed to assess the relative collagen VII protein levels and its location within the cornea. Additional IHC for inflammatory and fibrotic biomarkers alpha-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), proteinase 3, tenascin C and collagen III were performed. Clinical photographs documenting opacification of the corneas of animals of differing ages were assessed and scored independently by 2 examiners. Histology was then used to investigate morphologic changes. IHC and WB confirmed that these mice are deficient in collagen VII production at the level of the basement membrane when compared with wild-types. IHC showed anomalous deposition of collagen III throughout the stroma. Of the 5 biomarkers tested, TGF-β showed the strongest and most consistently staining. Photographs documented corneal opacities only in mice older than 10 weeks, opacities were not seen in younger animals. Histology showed multiple abnormalities, including epithelial hyperplasia, ulceration, fibrosis, edema, dysplasia, neovascularization and bullae formation. The collagen VII hypomorphic mouse shows reduced collagen VII production at the level of the corneal basement membrane. Corneal changes are similar to pathology seen in humans with this disease. The presence of anomalous stromal collagen III and TGF-β appear to be

  18. Skeletal Muscle Differentiation on a Chip Shows Human Donor Mesoangioblasts' Efficiency in Restoring Dystrophin in a Duchenne Muscular Dystrophy Model.

    Science.gov (United States)

    Serena, Elena; Zatti, Susi; Zoso, Alice; Lo Verso, Francesca; Tedesco, F Saverio; Cossu, Giulio; Elvassore, Nicola

    2016-12-01

    : Restoration of the protein dystrophin on muscle membrane is the goal of many research lines aimed at curing Duchenne muscular dystrophy (DMD). Results of ongoing preclinical and clinical trials suggest that partial restoration of dystrophin might be sufficient to significantly reduce muscle damage. Different myogenic progenitors are candidates for cell therapy of muscular dystrophies, but only satellite cells and pericytes have already entered clinical experimentation. This study aimed to provide in vitro quantitative evidence of the ability of mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes derived from DMD patients, using a microengineered model. We designed an ad hoc experimental strategy to miniaturize on a chip the standard process of muscle regeneration independent of variables such as inflammation and fibrosis. It is based on the coculture, at different ratios, of human dystrophin-positive myogenic progenitors and dystrophin-negative myoblasts in a substrate with muscle-like physiological stiffness and cell micropatterns. Results showed that both healthy myoblasts and mesoangioblasts restored dystrophin expression in DMD myotubes. However, mesoangioblasts showed unexpected efficiency with respect to myoblasts in dystrophin production in terms of the amount of protein produced (40% vs. 15%) and length of the dystrophin membrane domain (210-240 µm vs. 40-70 µm). These results show that our microscaled in vitro model of human DMD skeletal muscle validated previous in vivo preclinical work and may be used to predict efficacy of new methods aimed at enhancing dystrophin accumulation and distribution before they are tested in vivo, reducing time, costs, and variability of clinical experimentation. This study aimed to provide in vitro quantitative evidence of the ability of human mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes derived from

  19. Functional heterogeneity of cancer-associated fibroblasts from human colon tumors shows specific prognostic gene expression signature.

    Science.gov (United States)

    Herrera, Mercedes; Islam, Abul B M M K; Herrera, Alberto; Martín, Paloma; García, Vanesa; Silva, Javier; Garcia, Jose M; Salas, Clara; Casal, Ignacio; de Herreros, Antonio García; Bonilla, Félix; Peña, Cristina

    2013-11-01

    Cancer-associated fibroblasts (CAF) actively participate in reciprocal communication with tumor cells and with other cell types in the microenvironment, contributing to a tumor-permissive neighborhood and promoting tumor progression. The aim of this study is the characterization of how CAFs from primary human colon tumors promote migration of colon cancer cells. Primary CAF cultures from 15 primary human colon tumors were established. Their enrichment in CAFs was evaluated by the expression of various epithelial and myofibroblast specific markers. Coculture assays of primary CAFs with different colon tumor cells were performed to evaluate promigratory CAF-derived effects on cancer cells. Gene expression profiles were developed to further investigate CAF characteristics. Coculture assays showed significant differences in fibroblast-derived paracrine promigratory effects on cancer cells. Moreover, the association between CAFs' promigratory effects on cancer cells and classic fibroblast activation or stemness markers was observed. CAF gene expression profiles were analyzed by microarray to identify deregulated genes in different promigratory CAFs. The gene expression signature, derived from the most protumorogenic CAFs, was identified. Interestingly, this "CAF signature" showed a remarkable prognostic value for the clinical outcome of patients with colon cancer. Moreover, this prognostic value was validated in an independent series of 142 patients with colon cancer, by quantitative real-time PCR (qRT-PCR), with a set of four genes included in the "CAF signature." In summary, these studies show for the first time the heterogeneity of primary CAFs' effect on colon cancer cell migration. A CAF gene expression signature able to classify patients with colon cancer into high- and low-risk groups was identified.

  20. Anodal Transcranial Direct Current Stimulation Shows Minimal, Measure-Specific Effects on Dynamic Postural Control in Young and Older Adults: A Double Blind, Sham-Controlled Study.

    Science.gov (United States)

    Craig, Chesney E; Doumas, Michail

    2017-01-01

    We investigated whether stimulating the cerebellum and primary motor cortex (M1) using transcranial direct current stimulation (tDCS) could affect postural control in young and older adults. tDCS was employed using a double-blind, sham-controlled design, in which young (aged 18-35) and older adults (aged 65+) were assessed over three sessions, one for each stimulatory condition-M1, cerebellar and sham. The effect of tDCS on postural control was assessed using a sway-referencing paradigm, which induced platform rotations in proportion to the participant's body sway, thus assessing sensory reweighting processes. Task difficulty was manipulated so that young adults experienced a support surface that was twice as compliant as that of older adults, in order to minimise baseline age differences in postural sway. Effects of tDCS on postural control were assessed during, immediately after and 30 minutes after tDCS. Additionally, the effect of tDCS on corticospinal excitability was measured by evaluating motor evoked potentials using transcranial magnetic stimulation immediately after and 30 minutes after tDCS. Minimal effects of tDCS on postural control were found in the eyes open condition only, and this was dependent on the measure assessed and age group. For young adults, stimulation had only offline effects, as cerebellar stimulation showed higher mean power frequency (MPF) of sway 30 minutes after stimulation. For older adults, both stimulation conditions delayed the increase in sway amplitude witnessed between blocks one and two until stimulation was no longer active. In conclusion, despite tDCS' growing popularity, we would caution researchers to consider carefully the type of measures assessed and the groups targeted in tDCS studies of postural control.

  1. 'You don't show everyone your weakness': Older adults' views on using Family Group Conferencing to regain control and autonomy.

    Science.gov (United States)

    Metze, Rosalie N; Kwekkeboom, Rick H; Abma, Tineke A

    2015-08-01

    Family Group Conferencing (FGC), a model in which a person and his or her social network make their own 'care' plan, is used in youth care and might also be useful in elderly care to support older persons living at home. In Amsterdam, the Netherlands, FGC was implemented for older adults but they showed resistance. Reasons for this resistance have been researched and are described in this article. We examine existing views and attitudes of older adults concerning the use of FGC, and report on how older adults see the possibility to regain control over their lives using FGC. To do this, focus group sessions, duo interviews and individual interviews were held with older adults with varying characteristics: living at home, in sheltered housing, or in a home for the elderly; and living in urban, suburban or rural areas. Themes were: views on and contentment with the control and autonomy that they experience in their lives, and the willingness to use FGC to improve this. The main reasons for our respondents to resist FGC were: expecting people to be there for them without a FGC, not feeling ready yet for a FGC, feeling embarrassed when asking for help, being reluctant to open up about their problems, and having the fear of losing control when organizing a FGC. We conclude that, for this generation of older adults, FGC means losing control and autonomy rather than gaining it. To be appealing to older adults, a relational empowerment strengthening model should most likely be focused on reciprocity, peer-to-peer support, and solutions instead of problems. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability.

    Science.gov (United States)

    Boretto, Matteo; Cox, Benoit; Noben, Manuel; Hendriks, Nikolai; Fassbender, Amelie; Roose, Heleen; Amant, Frédéric; Timmerman, Dirk; Tomassetti, Carla; Vanhie, Arne; Meuleman, Christel; Ferrante, Marc; Vankelecom, Hugo

    2017-05-15

    The endometrium, which is of crucial importance for reproduction, undergoes dynamic cyclic tissue remodeling. Knowledge of its molecular and cellular regulation is poor, primarily owing to a lack of study models. Here, we have established a novel and promising organoid model from both mouse and human endometrium. Dissociated endometrial tissue, embedded in Matrigel under WNT-activating conditions, swiftly formed organoid structures that showed long-term expansion capacity, and reproduced the molecular and histological phenotype of the tissue's epithelium. The supplemented WNT level determined the type of mouse endometrial organoids obtained: high WNT yielded cystic organoids displaying a more differentiated phenotype than the dense organoids obtained in low WNT. The organoids phenocopied physiological responses of endometrial epithelium to hormones, including increased cell proliferation under estrogen and maturation upon progesterone. Moreover, the human endometrial organoids replicated the menstrual cycle under hormonal treatment at both the morpho-histological and molecular levels. Together, we established an organoid culture system for endometrium, reproducing tissue epithelium physiology and allowing long-term expansion. This novel model provides a powerful tool for studying mechanisms underlying the biology as well as the pathology of this key reproductive organ. © 2017. Published by The Company of Biologists Ltd.

  3. Isolation of Fully Human Antagonistic RON Antibodies Showing Efficient Block of Downstream Signaling and Cell Migration1

    Science.gov (United States)

    Gunes, Zeynep; Zucconi, Adriana; Cioce, Mario; Meola, Annalisa; Pezzanera, Monica; Acali, Stefano; Zampaglione, Immacolata; De Pratti, Valeria; Bova, Luca; Talamo, Fabio; Demartis, Anna; Monaci, Paolo; La Monica, Nicola; Ciliberto, Gennaro; Vitelli, Alessandra

    2011-01-01

    RON belongs to the c-MET family of receptor tyrosine kinases. As its well-known family member MET, RON and its ligand macrophage-stimulating protein have been implicated in the progression and metastasis of tumors and have been shown to be overexpressed in cancer. We generated and tested a large number of human monoclonal antibodies (mAbs) against human RON. Our screening yielded three high-affinity antibodies that efficiently block ligand-dependent intracellular AKT and MAPK signaling. This effect correlates with the strong reduction of ligand-activated migration of T47D breast cancer cell line. By cross-competition experiments, we showed that the antagonistic antibodies fall into three distinct epitope regions of the RON extracellular Sema domain. Notably, no inhibition of tumor growth was observed in different epithelial tumor xenografts in nude mice with any of the antibodies. These results suggest that distinct properties beside ligand antagonism are required for anti-RON mAbs to exert antitumor effects in vivo. PMID:21286376

  4. 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.

  5. 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.

  6. Adolescent C57BL/6J mice show elevated alcohol intake, but reduced taste aversion, as compared to adult mice: a potential behavioral mechanism for binge drinking.

    Science.gov (United States)

    Holstein, Sarah E; Spanos, Marina; Hodge, Clyde W

    2011-10-01

    Binge alcohol drinking during adolescence is a serious health problem that may increase future risk of an alcohol use disorder. Although there are several different procedures by which to preclinically model binge-like alcohol intake, limited-access procedures offer the advantage of achieving high voluntary alcohol intake and pharmacologically relevant blood alcohol concentrations (BACs). Therefore, in the current study, developmental differences in binge-like alcohol drinking using a limited-access cycling procedure were examined. In addition, as alcohol drinking has been negatively correlated with sensitivity to the aversive properties of alcohol, we examined developmental differences in sensitivity to an alcohol-induced conditioned taste aversion (CTA). Binge-like alcohol consumption was investigated in adolescent (4 weeks) and adult (10 weeks) male C57BL/6J mice for 2 to 4 h/d for 16 days. Developmental differences in sensitivity to an alcohol-induced CTA were examined in adolescent and adult mice, with saline or alcohol (3 or 4 g/kg) repeatedly paired with the intake of a novel tastant (NaCl). Adolescent mice showed a significant increase in alcohol intake as compared to adults, with adolescents achieving higher BACs and increasing alcohol consumption over successive cycles of the binge procedure. Conversely, adolescent mice exhibited a dose-dependent reduction in sensitivity to the aversive properties of alcohol, as compared to adult mice, with adolescent mice failing to develop a CTA to 3 g/kg alcohol. Finally, extinction of an alcohol CTA was observed following conditioning with a higher dose of alcohol in adolescent, versus adult, mice. These results indicate that adolescent mice consume more alcohol, per kilogram body weight, than adults in a binge-like model of alcohol drinking and demonstrate a blunted sensitivity to the conditioned aversive effects of alcohol. Overall, this supports a behavioral framework by which heightened binge alcohol intake during

  7. Studies Using an in Vitro Model Show Evidence of Involvement of Epithelial-Mesenchymal Transition of Human Endometrial Epithelial Cells in Human Embryo Implantation*

    Science.gov (United States)

    Uchida, Hiroshi; Maruyama, Tetsuo; Nishikawa-Uchida, Sayaka; Oda, Hideyuki; Miyazaki, Kaoru; Yamasaki, Akiko; Yoshimura, Yasunori

    2012-01-01

    Human embryo implantation is a critical multistep process consisting of embryo apposition/adhesion, followed by penetration and invasion. Through embryo penetration, the endometrial epithelial cell barrier is disrupted and remodeled by an unknown mechanism. We have previously developed an in vitro model for human embryo implantation employing the human choriocarcinoma cell line JAR and the human endometrial adenocarcinoma cell line Ishikawa. Using this model we have shown that stimulation with ovarian steroid hormones (17β-estradiol and progesterone, E2P4) and suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, enhances the attachment and adhesion of JAR spheroids to Ishikawa. In the present study we showed that the attachment and adhesion of JAR spheroids and treatment with E2P4 or SAHA individually induce the epithelial-mesenchymal transition (EMT) in Ishikawa cells. This was evident by up-regulation of N-cadherin and vimentin, a mesenchymal cell marker, and concomitant down-regulation of E-cadherin in Ishikawa cells. Stimulation with E2P4 or SAHA accelerated Ishikawa cell motility, increased JAR spheroid outgrowth, and enhanced the unique redistribution of N-cadherin, which was most prominent in proximity to the adhered spheroids. Moreover, an N-cadherin functional blocking antibody attenuated all events but not JAR spheroid adhesion. These results collectively provide evidence suggesting that E2P4- and implanting embryo-induced EMT of endometrial epithelial cells may play a pivotal role in the subsequent processes of human embryo implantation with functional control of N-cadherin. PMID:22174415

  8. Human Artificial Chromosomes with Alpha Satellite-Based De Novo Centromeres Show Increased Frequency of Nondisjunction and Anaphase Lag

    OpenAIRE

    Rudd, M. Katharine; Mays, Robert W.; Schwartz, Stuart; Willard, Huntington F.

    2003-01-01

    Human artificial chromosomes have been used to model requirements for human chromosome segregation and to explore the nature of sequences competent for centromere function. Normal human centromeres require specialized chromatin that consists of alpha satellite DNA complexed with epigenetically modified histones and centromere-specific proteins. While several types of alpha satellite DNA have been used to assemble de novo centromeres in artificial chromosome assays, the extent to which they fu...

  9. 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.

  10. 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.

  11. Laboratory, Epidemiological, and Human Intervention Studies Show That Tea (Camellia sinensis) May Be Useful in the Prevention of Obesity12

    OpenAIRE

    Grove, Kimberly A.; Lambert, Joshua D.

    2010-01-01

    Tea (Camellia sinensis, Theaceae) and tea polyphenols have been studied for the prevention of chronic diseases, including obesity. Obesity currently affects >20% of adults in the United States and is a risk factor for chronic diseases such as type II diabetes, cardiovascular disease, and cancer. Given this increasing public health concern, the use of dietary agents for the prevention of obesity would be of tremendous benefit. Whereas many laboratory studies have demonstrated the potential eff...

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

    Science.gov (United States)

    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

  13. I Show You How I Like You: Emotional Human-Robot Interaction through Facial Expression and Tactile Stimulation

    DEFF Research Database (Denmark)

    Canamero, Dolores; Fredslund, Jacob

    2001-01-01

    We report work on a LEGO robot that displays different emotional expressions in response to physical stimulation, for the purpose of social interaction with humans. This is a first step toward our longer-term goal of exploring believable emotional exchanges to achieve plausible interaction...... with a simple robot. Drawing inspiration from theories of human basic emotions, we implemented several prototypical expressions in the robot's caricatured face and conducted experiments to assess the recognizability of these expressions...

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

    Directory of Open Access Journals (Sweden)

    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

  15. Platelet-Rich Plasma Preparation Types Show Impact on Chondrogenic Differentiation, Migration, and Proliferation of Human Subchondral Mesenchymal Progenitor Cells.

    Science.gov (United States)

    Kreuz, Peter Cornelius; Krüger, Jan Philipp; Metzlaff, Sebastian; Freymann, Undine; Endres, Michaela; Pruss, Axel; Petersen, Wolf; Kaps, Christian

    2015-10-01

    To evaluate the chondrogenic potential of platelet concentrates on human subchondral mesenchymal progenitor cells (MPCs) as assessed by histomorphometric analysis of proteoglycans and type II collagen. Furthermore, the migratory and proliferative effect of platelet concentrates were assessed. Platelet-rich plasma (PRP) was prepared using preparation kits (Autologous Conditioned Plasma [ACP] Kit [Arthrex, Naples, FL]; Regen ACR-C Kit [Regen Lab, Le Mont-Sur-Lausanne, Switzerland]; and Dr.PRP Kit [Rmedica, Seoul, Republic of Korea]) by apheresis (PRP-A) and by centrifugation (PRP-C). In contrast to clinical application, freeze-and-thaw cycles were subsequently performed to activate platelets and to prevent medium coagulation by residual fibrinogen in vitro. MPCs were harvested from the cortico-spongious bone of femoral heads. Chondrogenic differentiation of MPCs was induced in high-density pellet cultures and evaluated by histochemical staining of typical cartilage matrix components. Migration of MPCs was assessed using a chemotaxis assay, and proliferation activity was measured by DNA content. MPCs cultured in the presence of 5% ACP, Regen, or Dr.PRP formed fibrous tissue, whereas MPCs stimulated with 5% PRP-A or PRP-C developed compact and dense cartilaginous tissue rich in type II collagen and proteoglycans. All platelet concentrates significantly (ACP, P = .00041; Regen, P = .00029; Dr.PRP, P = .00051; PRP-A, P platelet concentrates but one (Dr.PRP, P = .63) showed a proliferative effect on MPCs, as shown by significant increases (ACP, P = .027; Regen, P = .0029; PRP-A, P = .00021; and PRP-C, P = .00069) in DNA content. Platelet concentrates obtained by different preparation methods exhibit different potentials to stimulate chondrogenic differentiation, migration, and proliferation of MPCs. Platelet concentrates obtained by commercially available preparation kits failed to induce chondrogenic differentiation of MPCs, whereas highly standardized PRP

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

    Science.gov (United States)

    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.

  17. Human artificial chromosomes with alpha satellite-based de novo centromeres show increased frequency of nondisjunction and anaphase lag.

    Science.gov (United States)

    Rudd, M Katharine; Mays, Robert W; Schwartz, Stuart; Willard, Huntington F

    2003-11-01

    Human artificial chromosomes have been used to model requirements for human chromosome segregation and to explore the nature of sequences competent for centromere function. Normal human centromeres require specialized chromatin that consists of alpha satellite DNA complexed with epigenetically modified histones and centromere-specific proteins. While several types of alpha satellite DNA have been used to assemble de novo centromeres in artificial chromosome assays, the extent to which they fully recapitulate normal centromere function has not been explored. Here, we have used two kinds of alpha satellite DNA, DXZ1 (from the X chromosome) and D17Z1 (from chromosome 17), to generate human artificial chromosomes. Although artificial chromosomes are mitotically stable over many months in culture, when we examined their segregation in individual cell divisions using an anaphase assay, artificial chromosomes exhibited more segregation errors than natural human chromosomes (P artificial chromosomes missegregate over a fivefold range, the data suggest that variable centromeric DNA content and/or epigenetic assembly can influence the mitotic behavior of artificial chromosomes.

  18. 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

  19. A Mouse Model of Hyperproliferative Human Epithelium Validated by Keratin Profiling Shows an Aberrant Cytoskeletal Response to Injury

    Directory of Open Access Journals (Sweden)

    Samal Zhussupbekova

    2016-07-01

    Full Text Available A validated animal model would assist with research on the immunological consequences of the chronic expression of stress keratins KRT6, KRT16, and KRT17, as observed in human pre-malignant hyperproliferative epithelium. Here we examine keratin gene expression profile in skin from mice expressing the E7 oncoprotein of HPV16 (K14E7 demonstrating persistently hyperproliferative epithelium, in nontransgenic mouse skin, and in hyperproliferative actinic keratosis lesions from human skin. We demonstrate that K14E7 mouse skin overexpresses stress keratins in a similar manner to human actinic keratoses, that overexpression is a consequence of epithelial hyperproliferation induced by E7, and that overexpression further increases in response to injury. As stress keratins modify local immunity and epithelial cell function and differentiation, the K14E7 mouse model should permit study of how continued overexpression of stress keratins impacts on epithelial tumor development and on local innate and adaptive immunity.

  20. Global gene analysis of oocytes from early stages in human folliculogenesis shows high expression of novel genes in reproduction

    DEFF Research Database (Denmark)

    Markholt, Sara; Grøndahl, M L; Ernst, Erik

    2012-01-01

    The pool of primordial follicles in humans is laid down during embryonic development and follicles can remain dormant for prolonged intervals, often decades, until individual follicles resume growth. The mechanisms that induce growth and maturation of primordial follicles are poorly understood...... but follicles once activated either continue growth or undergo atresia. We have isolated pure populations of oocytes from human primordial, intermediate and primary follicles using laser capture micro-dissection microscopy and evaluated the global gene expression profiles by whole-genome microarray analysis......) and the mitochondrial-encoded ATPase6 (ATP6). Thus, the present study provides not only a technique to capture and perform transcriptome analysis of the sparse material of human oocytes from the earliest follicle stages but further includes a comprehensive basis for our understanding of the regulatory factors...

  1. 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

  2. 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.

  3. 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

  4. Lactotripeptides Show No Effect on Human Blood Pressure: Results from a double-blind randomized controlled trial

    NARCIS (Netherlands)

    Engberink, M.F.; Schouten, E.G.; Kok, F.J.; Mierlo, van L.A.J.; Brouwer, I.A.; Geleijnse, J.M.

    2008-01-01

    Milk-derived peptides with ACE-inhibiting properties may have antihypertensive effects in humans. We conducted a randomized double-blind placebo-controlled trial to examine the blood pressure lowering potential of 2 ACE-inhibiting lactotripeptides, ie, Isoleucine-Proline-Proline and

  5. Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers

    NARCIS (Netherlands)

    Lauc, G.; Huffman, J.E.; Pucic, M.; Zgaga, L.; Adamczyk, B.; Muzinic, A.; Novokmet, M.; Polasek, O.; Gornik, O.; Kristic, J.; Keser, T.; Vitart, V.; Scheijen, B.; Uh, H.W.; Molokhia, M.; Patrick, A.L.; McKeigue, P.; Kolcic, I.; Lukic, I.K.; Swann, O.; Leeuwen, F.N. van; Ruhaak, L.R.; Houwing-Duistermaat, J.J.; Slagboom, P.E.; Beekman, M.; Craen, A.J. de; Deelder, A.M.; Zeng, Q.; Wang, W.; Hastie, N.D.; Gyllensten, U.; Wilson, J.F.; Wuhrer, M.; Wright, A.F.; Rudd, P.M.; Hayward, C.; Aulchenko, Y.; Campbell, H.; Rudan, I.

    2013-01-01

    Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. After isolating IgG from human plasma, we performed 77 quantitative

  6. 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.

  7. Human and Animal Isolates of Yersinia enterocolitica Show Significant Serotype-Specific Colonization and Host-Specific Immune Defense Properties

    Science.gov (United States)

    Schaake, Julia; Kronshage, Malte; Uliczka, Frank; Rohde, Manfred; Knuuti, Tobias; Strauch, Eckhard; Fruth, Angelika; Wos-Oxley, Melissa

    2013-01-01

    Yersinia enterocolitica is a human pathogen that is ubiquitous in livestock, especially pigs. The bacteria are able to colonize the intestinal tract of a variety of mammalian hosts, but the severity of induced gut-associated diseases (yersiniosis) differs significantly between hosts. To gain more information about the individual virulence determinants that contribute to colonization and induction of immune responses in different hosts, we analyzed and compared the interactions of different human- and animal-derived isolates of serotypes O:3, O:5,27, O:8, and O:9 with murine, porcine, and human intestinal cells and macrophages. The examined strains exhibited significant serotype-specific cell binding and entry characteristics, but adhesion and uptake into different host cells were not host specific and were independent of the source of the isolate. In contrast, survival and replication within macrophages and the induced proinflammatory response differed between murine, porcine, and human macrophages, suggesting a host-specific immune response. In fact, similar levels of the proinflammatory cytokine macrophage inflammatory protein 2 (MIP-2) were secreted by murine bone marrow-derived macrophages with all tested isolates, but the equivalent interleukin-8 (IL-8) response of porcine bone marrow-derived macrophages was strongly serotype specific and considerably lower in O:3 than in O:8 strains. In addition, all tested Y. enterocolitica strains caused a considerably higher level of secretion of the anti-inflammatory cytokine IL-10 by porcine than by murine macrophages. This could contribute to limiting the severity of the infection (in particular of serotype O:3 strains) in pigs, which are the primary reservoir of Y. enterocolitica strains pathogenic to humans. PMID:23959720

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

    Science.gov (United States)

    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

  9. MRI of Mouse Models for Gliomas Shows Similarities to Humans and Can Be Used to Identify Mice for Preclinical Trials

    Directory of Open Access Journals (Sweden)

    Jason A. Koutcher

    2002-01-01

    Full Text Available Magnetic resonance imaging (MRI has been utilized for screening and detecting brain tumors in mice based upon their imaging characteristics appearance and their pattern of enhancement. Imaging of these tumors reveals many similarities to those observed in humans with identical pathology. Specifically, high-grade murine gliomas have histologic characteristics of glioblastoma multiforme (GBM with contrast enhancement after intravenous administration of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA, implying disruption of the blood-brain barrier in these tumors. In contrast, low-grade murine oligodendrogliomas do not reveal contrast enhancement, similar to human tumors. MRI can be used to identify mice with brain neoplasms as inclusion criteria in preclinical trials.

  10. Measure, Then Show: Grasping Human Evolution Through an Inquiry-Based, Data-driven Hominin Skulls Lab.

    Directory of Open Access Journals (Sweden)

    Chris N Bayer

    Full Text Available Incomprehension and denial of the theory of evolution among high school students has been observed to also occur when teachers are not equipped to deliver a compelling case also for human evolution based on fossil evidence. This paper assesses the outcomes of a novel inquiry-based paleoanthropology lab teaching human evolution to high-school students. The inquiry-based Be a Paleoanthropologist for a Day lab placed a dozen hominin skulls into the hands of high-school students. Upon measuring three variables of human evolution, students explain what they have observed and discuss findings. In the 2013/14 school year, 11 biology classes in 7 schools in the Greater New Orleans area participated in this lab. The interviewed teacher cohort unanimously agreed that the lab featuring hominin skull replicas and stimulating student inquiry was a pedagogically excellent method of delivering the subject of human evolution. First, the lab's learning path of transforming facts to data, information to knowledge, and knowledge to acceptance empowered students to themselves execute part of the science that underpins our understanding of deep time hominin evolution. Second, although challenging, the hands-on format of the lab was accessible to high-school students, most of whom were readily able to engage the lab's scientific process. Third, the lab's exciting and compelling pedagogy unlocked higher order thinking skills, effectively activating the cognitive, psychomotor and affected learning domains as defined in Bloom's taxonomy. Lastly, the lab afforded students a formative experience with a high degree of retention and epistemic depth. Further study is warranted to gauge the degree of these effects.

  11. Measure, Then Show: Grasping Human Evolution Through an Inquiry-Based, Data-driven Hominin Skulls Lab.

    Science.gov (United States)

    Bayer, Chris N; Luberda, Michael

    2016-01-01

    Incomprehension and denial of the theory of evolution among high school students has been observed to also occur when teachers are not equipped to deliver a compelling case also for human evolution based on fossil evidence. This paper assesses the outcomes of a novel inquiry-based paleoanthropology lab teaching human evolution to high-school students. The inquiry-based Be a Paleoanthropologist for a Day lab placed a dozen hominin skulls into the hands of high-school students. Upon measuring three variables of human evolution, students explain what they have observed and discuss findings. In the 2013/14 school year, 11 biology classes in 7 schools in the Greater New Orleans area participated in this lab. The interviewed teacher cohort unanimously agreed that the lab featuring hominin skull replicas and stimulating student inquiry was a pedagogically excellent method of delivering the subject of human evolution. First, the lab's learning path of transforming facts to data, information to knowledge, and knowledge to acceptance empowered students to themselves execute part of the science that underpins our understanding of deep time hominin evolution. Second, although challenging, the hands-on format of the lab was accessible to high-school students, most of whom were readily able to engage the lab's scientific process. Third, the lab's exciting and compelling pedagogy unlocked higher order thinking skills, effectively activating the cognitive, psychomotor and affected learning domains as defined in Bloom's taxonomy. Lastly, the lab afforded students a formative experience with a high degree of retention and epistemic depth. Further study is warranted to gauge the degree of these effects.

  12. Recombinant human melatonin receptor MT1 isolated in mixed detergents shows pharmacology similar to that in mammalian cell membranes.

    Directory of Open Access Journals (Sweden)

    Christel Logez

    Full Text Available The human melatonin MT1 receptor-belonging to the large family of G protein-coupled receptors (GPCRs-plays a key role in circadian rhythm regulation and is notably involved in sleep disorders and depression. Structural and functional information at the molecular level are highly desired for fine characterization of this receptor; however, adequate techniques for isolating soluble MT1 material suitable for biochemical and biophysical studies remain lacking. Here we describe the evaluation of a panel of constructs and host systems for the production of recombinant human MT1 receptors, and the screening of different conditions for their solubilization and purification. Our findings resulted in the establishment of an original strategy using a mixture of Fos14 and CHAPS detergents to extract and purify a recombinant human MT1 from Pichia pastoris membranes. This procedure enabled the recovery of relatively pure, monomeric and ligand-binding active MT1 receptor in the near-milligram range. A comparative study based on extensive ligand-binding characterization highlighted a very close correlation between the pharmacological profiles of MT1 purified from yeast and the same receptor present in mammalian cell membranes. The high quality of the purified MT1 was further confirmed by its ability to activate its cognate Gαi protein partner when reconstituted in lipid discs, thus opening novel paths to investigate this receptor by biochemical and biophysical approaches.

  13. Recombinant human melatonin receptor MT1 isolated in mixed detergents shows pharmacology similar to that in mammalian cell membranes.

    Science.gov (United States)

    Logez, Christel; Berger, Sylvie; Legros, Céline; Banères, Jean-Louis; Cohen, William; Delagrange, Philippe; Nosjean, Olivier; Boutin, Jean A; Ferry, Gilles; Simonin, Frédéric; Wagner, Renaud

    2014-01-01

    The human melatonin MT1 receptor-belonging to the large family of G protein-coupled receptors (GPCRs)-plays a key role in circadian rhythm regulation and is notably involved in sleep disorders and depression. Structural and functional information at the molecular level are highly desired for fine characterization of this receptor; however, adequate techniques for isolating soluble MT1 material suitable for biochemical and biophysical studies remain lacking. Here we describe the evaluation of a panel of constructs and host systems for the production of recombinant human MT1 receptors, and the screening of different conditions for their solubilization and purification. Our findings resulted in the establishment of an original strategy using a mixture of Fos14 and CHAPS detergents to extract and purify a recombinant human MT1 from Pichia pastoris membranes. This procedure enabled the recovery of relatively pure, monomeric and ligand-binding active MT1 receptor in the near-milligram range. A comparative study based on extensive ligand-binding characterization highlighted a very close correlation between the pharmacological profiles of MT1 purified from yeast and the same receptor present in mammalian cell membranes. The high quality of the purified MT1 was further confirmed by its ability to activate its cognate Gαi protein partner when reconstituted in lipid discs, thus opening novel paths to investigate this receptor by biochemical and biophysical approaches.

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

    Science.gov (United States)

    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...

  15. 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

  16. Age distribution of human gene families shows significant roles of both large- and small-scale duplications in vertebrate evolution.

    Science.gov (United States)

    Gu, Xun; Wang, Yufeng; Gu, Jianying

    2002-06-01

    The classical (two-round) hypothesis of vertebrate genome duplication proposes two successive whole-genome duplication(s) (polyploidizations) predating the origin of fishes, a view now being seriously challenged. As the debate largely concerns the relative merits of the 'big-bang mode' theory (large-scale duplication) and the 'continuous mode' theory (constant creation by small-scale duplications), we tested whether a significant proportion of paralogous genes in the contemporary human genome was indeed generated in the early stage of vertebrate evolution. After an extensive search of major databases, we dated 1,739 gene duplication events from the phylogenetic analysis of 749 vertebrate gene families. We found a pattern characterized by two waves (I, II) and an ancient component. Wave I represents a recent gene family expansion by tandem or segmental duplications, whereas wave II, a rapid paralogous gene increase in the early stage of vertebrate evolution, supports the idea of genome duplication(s) (the big-bang mode). Further analysis indicated that large- and small-scale gene duplications both make a significant contribution during the early stage of vertebrate evolution to build the current hierarchy of the human proteome.

  17. Degradation of p53 by human Alphapapillomavirus E6 proteins shows a stronger correlation with phylogeny than oncogenicity.

    Directory of Open Access Journals (Sweden)

    Leiping Fu

    2010-09-01

    Full Text Available Human Papillomavirus (HPV E6 induced p53 degradation is thought to be an essential activity by which high-risk human Alphapapillomaviruses (alpha-HPVs contribute to cervical cancer development. However, most of our understanding is derived from the comparison of HPV16 and HPV11. These two viruses are relatively distinct viruses, making the extrapolation of these results difficult. In the present study, we expand the tested strains (types to include members of all known HPV species groups within the Alphapapillomavirus genus.We report the biochemical activity of E6 proteins from 27 HPV types representing all alpha-HPV species groups to degrade p53 in human cells. Expression of E6 from all HPV types epidemiologically classified as group 1 carcinogens significantly reduced p53 levels. However, several types not associated with cancer (e.g., HPV53, HPV70 and HPV71 were equally active in degrading p53. HPV types within species groups alpha 5, 6, 7, 9 and 11 share a most recent common ancestor (MRCA and all contain E6 ORFs that degrade p53. A unique exception, HPV71 E6 ORF that degraded p53 was outside this clade and is one of the most prevalent HPV types infecting the cervix in a population-based study of 10,000 women. Alignment of E6 ORFs identified an amino acid site that was highly correlated with the biochemical ability to degrade p53. Alteration of this amino acid in HPV71 E6 abrogated its ability to degrade p53, while alteration of this site in HPV71-related HPV90 and HPV106 E6s enhanced their capacity to degrade p53.These data suggest that the alpha-HPV E6 proteins' ability to degrade p53 is an evolved phenotype inherited from a most recent common ancestor of the high-risk species that does not always segregate with carcinogenicity. In addition, we identified an amino-acid residue strongly correlated with viral p53 degrading potential.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  20. 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.

  1. MUTZ-3 derived Langerhans cells in human skin equivalents show differential migration and phenotypic plasticity after allergen or irritant exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kosten, Ilona J.; Spiekstra, Sander W. [Department of Dermatology, VU University Medical Center, Amsterdam (Netherlands); Gruijl, Tanja D. de [Department of Dermatology Medical Oncology, VU University Medical Center, Amsterdam (Netherlands); Gibbs, Susan, E-mail: s.gibbs@acta.nl [Department of Dermatology, VU University Medical Center, Amsterdam (Netherlands); Department of Oral Cell Biology, Academic Center for Dentistry (ACTA), Amsterdam (Netherlands)

    2015-08-15

    After allergen or irritant exposure, Langerhans cells (LC) undergo phenotypic changes and exit the epidermis. In this study we describe the unique ability of MUTZ-3 derived Langerhans cells (MUTZ-LC) to display similar phenotypic plasticity as their primary counterparts when incorporated into a physiologically relevant full-thickness skin equivalent model (SE-LC). We describe differences and similarities in the mechanisms regulating LC migration and plasticity upon allergen or irritant exposure. The skin equivalent consisted of a reconstructed epidermis containing primary differentiated keratinocytes and CD1a{sup +} MUTZ-LC on a primary fibroblast-populated dermis. Skin equivalents were exposed to a panel of allergens and irritants. Topical exposure to sub-toxic concentrations of allergens (nickel sulfate, resorcinol, cinnamaldehyde) and irritants (Triton X-100, SDS, Tween 80) resulted in LC migration out of the epidermis and into the dermis. Neutralizing antibody to CXCL12 blocked allergen-induced migration, whereas anti-CCL5 blocked irritant-induced migration. In contrast to allergen exposure, irritant exposure resulted in cells within the dermis becoming CD1a{sup −}/CD14{sup +}/CD68{sup +} which is characteristic of a phenotypic switch of MUTZ-LC to a macrophage-like cell in the dermis. This phenotypic switch was blocked with anti-IL-10. Mechanisms previously identified as being involved in LC activation and migration in native human skin could thus be reproduced in the in vitro constructed skin equivalent model containing functional LC. This model therefore provides a unique and relevant research tool to study human LC biology in situ under controlled in vitro conditions, and will provide a powerful tool for hazard identification, testing novel therapeutics and identifying new drug targets. - Highlights: • MUTZ-3 derived Langerhans cells integrated into skin equivalents are fully functional. • Anti-CXCL12 blocks allergen-induced MUTZ-LC migration.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  6. Plectasin shows intracellular activity against Staphylococcus aureus in human THP-1 monocytes and in a mouse peritonitis model

    DEFF Research Database (Denmark)

    Brinch, Karoline Sidelmann; Sandberg, Anne; Baudoux, Pierre

    2009-01-01

    was maintained (maximal relative efficacy [E(max)], 1.0- to 1.3-log reduction in CFU) even though efficacy was inferior to that of extracellular killing (E(max), >4.5-log CFU reduction). Animal studies included a novel use of the mouse peritonitis model, exploiting extra- and intracellular differentiation assays...... concentration. These findings stress the importance of performing studies of extra- and intracellular activity since these features cannot be predicted from traditional MIC and killing kinetic studies. Application of both the THP-1 and the mouse peritonitis models showed that the in vitro results were similar...

  7. 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…

  8. Brain natriuretic peptide is a potent vasodilator in aged human microcirculation and shows a blunted response in heart failure patients

    DEFF Research Database (Denmark)

    Edvinsson, Marie-Louise; Uddman, Erik; Edvinsson, Lars

    2014-01-01

    in the forearm was measured by laser Doppler Flowmetry. Local heating (+44°C, 10 min) was used to evoke a maximum local dilator response. RESULTS: Non-invasive iontophoretic administration of either BNP or acetylcholine (ACh), a known endothelium-dependent dilator, elicited an increase in local flow. The nitric......, the vasodilator responses to ACh and to local heating were only somewhat attenuated in CHF patients. Thus, dilator capacity and nitric oxide signalling were not affected to the same extent as BNP-mediated dilation, indicating a specific downregulation of the latter response. CONCLUSIONS: The findings show...... for the first time that microvascular responses to BNP are markedly reduced in CHF patients. This is consistent with the hypothesis of BNP receptor function is downregulated in CHF....

  9. 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.

  10. Adult Education and Human Capital: Leadership from the Fortune 500.

    Science.gov (United States)

    Palmer, Teresa M.

    1992-01-01

    A survey of 333 Fortune 500 firms received 81 replies indicating that (1) two-thirds formally recognized the value of human resources; (2) most had changed corporate policy regarding human capital; and (3) most training was provided in the ares of new employee orientation, current job needs, customer relations, personal development, and…

  11. 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.

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

    Science.gov (United States)

    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.

  13. Human Peripheral Blood Mononuclear Cells Exhibit Heterogeneous CD52 Expression Levels and Show Differential Sensitivity to Alemtuzumab Mediated Cytolysis

    Science.gov (United States)

    Rao, Sambasiva P.; Sancho, Jose; Campos-Rivera, Juanita; Boutin, Paula M.; Severy, Peter B.; Weeden, Timothy; Shankara, Srinivas; Roberts, Bruce L.; Kaplan, Johanne M.

    2012-01-01

    Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs) from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs) display the highest number while natural killer (NK) cells, plasmacytoid dendritic cells (pDCs) and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC) studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs) on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact. PMID:22761788

  14. Image-based multiscale mechanical modeling shows the importance of structural heterogeneity in the human lumbar facet capsular ligament.

    Science.gov (United States)

    Zarei, Vahhab; Liu, Chao J; Claeson, Amy A; Akkin, Taner; Barocas, Victor H

    2017-08-01

    The lumbar facet capsular ligament (FCL) primarily consists of aligned type I collagen fibers that are mainly oriented across the joint. The aim of this study was to characterize and incorporate in-plane local fiber structure into a multiscale finite element model to predict the mechanical response of the FCL during in vitro mechanical tests, accounting for the heterogeneity in different scales. Characterization was accomplished by using entire-domain polarization-sensitive optical coherence tomography to measure the fiber structure of cadaveric lumbar FCLs ([Formula: see text]). Our imaging results showed that fibers in the lumbar FCL have a highly heterogeneous distribution and are neither isotropic nor completely aligned. The averaged fiber orientation was [Formula: see text] ([Formula: see text] in the inferior region and [Formula: see text] in the middle and superior regions), with respect to lateral-medial direction (superior-medial to inferior-lateral). These imaging data were used to construct heterogeneous structural models, which were then used to predict experimental gross force-strain behavior and the strain distribution during equibiaxial and strip biaxial tests. For equibiaxial loading, the structural model fit the experimental data well but underestimated the lateral-medial forces by [Formula: see text]16% on average. We also observed pronounced heterogeneity in the strain field, with stretch ratios for different elements along the lateral-medial axis of sample typically ranging from about 0.95 to 1.25 during a 12% strip biaxial stretch in the lateral-medial direction. This work highlights the multiscale structural and mechanical heterogeneity of the lumbar FCL, which is significant both in terms of injury prediction and microstructural constituents' (e.g., neurons) behavior.

  15. Human peripheral blood mononuclear cells exhibit heterogeneous CD52 expression levels and show differential sensitivity to alemtuzumab mediated cytolysis.

    Directory of Open Access Journals (Sweden)

    Sambasiva P Rao

    Full Text Available Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs display the highest number while natural killer (NK cells, plasmacytoid dendritic cells (pDCs and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact.

  16. 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....

  17. CCL2 binding is CCR2 independent in primary adult human astrocytes.

    Science.gov (United States)

    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.

  18. The sodium-bicarbonate cotransporter NBCe2 (slc4a5) expressed in human renal proximal tubules shows increased apical expression under high-salt conditions.

    Science.gov (United States)

    Gildea, John J; Xu, Peng; Carlson, Julia M; Gaglione, Robert T; Bigler Wang, Dora; Kemp, Brandon A; Reyes, Camellia M; McGrath, Helen E; Carey, Robert M; Jose, Pedro A; Felder, Robin A

    2015-12-01

    The electrogenic sodium bicarbonate cotransporter (NBCe2) is encoded by SLC4A5, variants of which have been associated with salt sensitivity of blood pressure, which affects 25% of the adult population. NBCe2 is thought to mediate sodium bicarbonate cotransport primarily in the renal collecting duct, but NBCe2 mRNA is also found in the rodent renal proximal tubule (RPT). The protein expression or function of NBCe2 has not been demonstrated in the human RPT. We validated an NBCe2 antibody by shRNA and Western blot analysis, as well as overexpression of an epitope-tagged NBCe2 construct in both RPT cells (RPTCs) and human embryonic kidney 293 (HEK293) cells. Using this validated NBCe2 antibody, we found NBCe2 protein expression in the RPT of fresh and frozen human kidney slices, RPTCs isolated from human urine, and isolated RPTC apical membrane. Under basal conditions, NBCe2 was primarily found in the Golgi, while NBCe1 was primarily found at the basolateral membrane. Following an acute short-term increase in intracellular sodium, NBCe2 expression was increased at the apical membrane in cultured slices of human kidney and polarized, immortalized RPTCs. Sodium bicarbonate transport was increased by monensin and overexpression of NBCe2, decreased by NBCe2 shRNA, but not by NBCe1 shRNA, and blocked by 2,2'-(1,2-ethenediyl)bis[5-isothiocyanato-benzenesulfonic acid]. NBCe2 could be important in apical sodium and bicarbonate cotransport under high-salt conditions; the implication of the ex vivo studies to the in vivo situation when salt intake is increased remains unclear. Therefore, future studies will examine the role of NBCe2 in mediating increased renal sodium transport in humans whose blood pressures are elevated by an increase in sodium intake. Copyright © 2015 the American Physiological Society.

  19. 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.

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

    Science.gov (United States)

    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.

  1. Hesperetin induces melanin production in adult human epidermal melanocytes.

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  4. A self administered executive functions ecological questionnaire (the Behavior Rating Inventory of Executive Function - Adult Version shows impaired scores in a sample of patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Andrei Szöke

    2013-02-01

    Full Text Available Subjective measurements of cognition have seldom been used in schizophrenia. This is mainly due to the assumption that such measurements lack sensitivity in a disorder characterized by poor insight. We investigated the capacity of BRIEF-A (Behavior Rating Inventory of Executive Function - Adult Version: a self-administered, ecological questionnaire to identify executive deficits in adults with schizophrenia. The global score and each domain-specific score was significantly lower in patients than in healthy controls. BRIEF-A could be a useful complement to objective measurements, providing a subjective assessment of everyday consequences of executive dysfunction in patients with schizophrenia.

  5. 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

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

    Science.gov (United States)

    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.

  7. 'You don't show everyone your weakness': Older adults' views on using Family Group Conferencing to regain control and autonomy

    NARCIS (Netherlands)

    Metze, R.N.; Kwekkeboom, R.H.; Abma, T.A.

    2015-01-01

    Aim: Family Group Conferencing (FGC), a model in which a person and his or her social network make their own 'care' plan, is used in youth care and might also be useful in elderly care to support older persons living at home. In Amsterdam, the Netherlands, FGC was implemented for older adults but

  8. Resident aerobic microbiota of the adult human nasal cavity

    DEFF Research Database (Denmark)

    Rasmussen, TT; Kirkeby Nielsen, LP; Poulsen, Knud

    2000-01-01

    Recent evidence strongly suggests that the microbiota of the nasal cavity plays a crucial role in determining the reaction patterns of the mucosal and systemic immune system. However, little is known about the normal microbiota of the nasal cavity. The purpose of this study was to determine...... the microbiota in different parts of the nasal cavity and to develop and evaluate methods for this purpose. Samples were collected from 10 healthy adults by nasal washes and by swabbing of the mucosa through a sterile introduction device. Both methods gave results that were quantitatively and qualitatively...... reproducible, and revealed significant differences in the density of the nasal microbiota between individuals. The study revealed absence of gram-negative bacteria that are regular members of the commensal microbiota of the pharynx. Likewise, viridans type streptococci were sparsely represented. The nasal...

  9. An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells

    KAUST Repository

    Ali, Amal J.; AbuElela, Ayman; Merzaban, Jasmeen

    2017-01-01

    -selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells. We showed that CD44 acts as a functional E-selectin ligand when expressed on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein

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

    Directory of Open Access Journals (Sweden)

    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

  11. Phenotypic characterization of an older adult male with late-onset epilepsy and a novel mutation in ASXL3 shows overlap with the associated Bainbridge-Ropers syndrome

    Directory of Open Access Journals (Sweden)

    Verhoeven W

    2018-03-01

    Full Text Available Willem Verhoeven,1,2 Jos Egger,1,3 Emmy Räkers,4 Arjen van Erkelens,5 Rolph Pfundt,5 Marjolein H Willemsen5 1Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, the Netherlands; 2Department of Psychiatry, Erasmus University Medical Centre, Rotterdam, the Netherlands; 3Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands; 4ASVZ, Centre for People with Intellectual Disabilities, Sliedrecht, the Netherlands; 5Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands Abstract: The additional sex combs like 3 gene is considered to be causative for the rare Bainbridge-Ropers syndrome (BRPS, which is characterized by severe intellectual disability, neonatal hypotonia, nearly absent development of speech and language as well as several facial dysmorphisms. Apart from disruptive autistiform behaviors, sleep disturbances and epileptic phenomena may be present. Here, a 47-year-old severely intellectually disabled male is described in whom exome sequencing disclosed a novel heterozygous frameshift mutation in the ASXL3 gene leading to a premature stopcodon in the last part of the last exon. Mutations in this very end 3' of the gene have not been reported before in BRPS. The phenotypical presentation of the patient including partially therapy-resistant epilepsy starting in later adulthood shows overlap with BRPS, and it was therefore concluded that the phenotype is likely explained by the identified mutation in ASXL3. Keywords: Bainbridge-Ropers syndrome, ASLX3, frameshift mutation, epilepsy, intellectual disability, array analysis, whole exome sequencing, autism spectrum disorder

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

    Science.gov (United States)

    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.

  13. 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.

  14. 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  17. 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.

  18. 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.

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

    Science.gov (United States)

    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.

  20. ERP C250 shows the elderly (cognitively normal, Alzheimer's disease) store more stimuli in short-term memory than Young Adults do.

    Science.gov (United States)

    Chapman, Robert M; Gardner, Margaret N; Mapstone, Mark; Klorman, Rafael; Porsteinsson, Anton P; Dupree, Haley M; Antonsdottir, Inga M; Kamalyan, Lily

    2016-06-01

    To determine how aging and dementia affect the brain's initial storing of task-relevant and irrelevant information in short-term memory. We used brain Event-Related Potentials (ERPs) to measure short-term memory storage (ERP component C250) in 36 Young Adults, 36 Normal Elderly, and 36 early-stage AD subjects. Participants performed the Number-Letter task, a cognitive paradigm requiring memory storage of a first relevant stimulus to compare it with a second stimulus. In Young Adults, C250 was more positive for the first task-relevant stimulus compared to all other stimuli. C250 in Normal Elderly and AD subjects was roughly the same to relevant and irrelevant stimuli in Intratrial Parts 1-3 but not 4. The AD group had lower C250 to relevant stimuli in part 1. Both normal aging and dementia cause less differentiation of relevant from irrelevant information in initial storage. There was a large aging effect involving differences in the pattern of C250 responses of the Young Adult versus the Normal Elderly/AD groups. Also, a potential dementia effect was obtained. C250 is a candidate tool for measuring short-term memory performance on a biological level, as well as a potential marker for memory changes due to normal aging and dementia. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. 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…

  4. 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…

  5. 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).…

  6. 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

  7. 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…

  8. 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 ...

  9. 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

  10. Adults with developmental dyslexia show selective impairments in time-based and self-initiated prospective memory: Self-report and clinical evidence.

    Science.gov (United States)

    Smith-Spark, James H; Zięcik, Adam P; Sterling, Christopher

    2017-03-01

    Prospective memory (PM; memory for delayed intentions) would seem to be impaired in dyslexia but evidence is currently limited in scope. There is a need, therefore, firstly, to explore PM under controlled conditions using a broader range of PM tasks than used previously and, secondly, to determine whether objectively measured and self-reported PM problems can be found in the same individuals with dyslexia. The responses of 30 adults with dyslexia were compared with those of 30 IQ-matched adults without dyslexia on a self-report and a clinical measure of PM. Dyslexia-related deficits were shown on the clinical measure overall and, more particularly, when PM responses had to be made to cues based on time rather than environmental events. Adults with dyslexia were also more likely to forget to carry out an intention under naturalistic conditions 24h later. On the self-report questionnaire, the group with dyslexia reported significantly more frequent problems with PM overall, despite using more techniques to aid their memory. In particular, problems were identified with longer-term PM tasks and PM which had to be self-initiated. Dyslexia-related PM deficits were found under both laboratory and everyday conditions in the same participants; the first time that this has been demonstrated. These findings support previous experimental research which has highlighted dyslexia-related deficits in PM when the enacting of intentions is based on time cues and/or has to be self-initiated rather than being in prompted by environmental events. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  12. 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

  13. 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.

  14. Candida tropicalis from veterinary and human sources shows similar in vitro hemolytic activity, antifungal biofilm susceptibility and pathogenesis against Caenorhabditis elegans.

    Science.gov (United States)

    Brilhante, Raimunda Sâmia Nogueira; Oliveira, Jonathas Sales de; Evangelista, Antônio José de Jesus; Serpa, Rosana; Silva, Aline Lobão da; Aguiar, Felipe Rodrigues Magalhães de; Pereira, Vandbergue Santos; Castelo-Branco, Débora de Souza Collares Maia; Pereira-Neto, Waldemiro Aquino; Cordeiro, Rossana de Aguiar; Sidrim, José Júlio Costa; Rocha, Marcos Fábio Gadelha

    2016-08-30

    The aim of this study was to evaluate the in vitro hemolytic activity and biofilm antifungal susceptibility of veterinary and human Candida tropicalis strains, as well as their pathogenesis against Caenorhabditis elegans. Twenty veterinary isolates and 20 human clinical isolates of C. tropicalis were used. The strains were evaluated for their hemolytic activity and biofilm production. Biofilm susceptibility to itraconazole, fluconazole, voriconazole, amphotericin B and caspofungin was assessed using broth microdilution assay. The in vivo evaluation of strain pathogenicity was investigated using the nematode C. elegans. Hemolytic factor was observed in 95% of the strains and 97.5% of the isolates showed ability to form biofilm. Caspofungin and amphotericin B showed better results than azole antifungals against mature biofilms. Paradoxical effect on mature biofilm metabolic activity was observed at elevated concentrations of caspofungin (8-64μg/mL). Azole antifungals were not able to inhibit mature C. tropicalis biofilms, even at the higher tested concentrations. High mortality rates of C. elegans were observed when the worms were exposed to with C. tropicalis strains, reaching up to 96%, 96h after exposure of the worms to C. tropicalis strains. These results reinforce the high pathogenicity of C. tropicalis from veterinary and human sources and show the effectiveness of caspofungin and amphotericin B against mature biofilms of this species. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. 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…

  16. Neuroscience of Human Social Interactions and Adult Attachment Style

    Directory of Open Access Journals (Sweden)

    Pascal eVrticka

    2012-07-01

    Full Text Available Since its first description four decades ago, attachment theory has become one of the principal developmental psychological frameworks for describing the role of individual differences in the establishment and maintenance of social bonds between people. Yet, still little is known about the neurobiological underpinnings of attachment orientations and their well-established impact on a range of social and affective behaviors. In the present review, we summarize data from recent studies using cognitive and imaging approaches to characterize attachment styles and their effect on emotion and social cognition. We propose a functional neuroanatomical framework to integrate the key brain mechanisms involved in the perception and regulation of social emotional information, and their modulation by individual differences in terms of secure versus insecure (more specifically avoidant, anxious, or resolved vs. unresolved attachment traits. This framework describes how each individual’s attachment style (built through interactions between personal relationship history and predispositions may influence the encoding of approach versus aversion tendencies (safety versus threat in social encounters, implicating the activation of a network of subcortical (amygdala, hippocampus, striatum and cortical (insula, cingulate limbic areas. These basic and automatic affective mentalization mechanisms are in turn modulated by more elaborate and voluntary cognitive mentalization processes, subserving theory of mind, cognitive control, and emotion regulation capacities, implicating a distinct network (in medial prefrontal cortex, superior temporal sulcus, and temporo-parietal junction, among others. Such research does not only help better understand the neural underpinnings of human social behavior, but also provides important insights on psychopathological conditions where attachment dysregulations is likely to play an important (causal role.

  17. 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.

  18. 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....

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

    Science.gov (United States)

    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.

  20. White matter sexual dimorphism of the adult human brain

    Directory of Open Access Journals (Sweden)

    Bourisly Ali K.

    2017-05-01

    Full Text Available Sex-biased psychophysiology, behavior, brain function, and conditions are extensive, yet underlying structural brain mechanisms remain unclear. There is contradicting evidence regarding sexual dimorphism when it comes to brain structure, and there is still no consensus on whether or not there exists such a dimorphism for brain white matter. Therefore, we conducted a voxel-based morphometry (VBM analysis along with global volume analysis for white matter across sex. We analyzed 384 T1-weighted MRI brain images (192 male, 192 female to investigate any differences in white matter (WM between males and females. In the VBM analysis, we found males to have larger WM, compared to females, in occipital, temporal, insular, parietal, and frontal brain regions. In contrast, females showed only one WM region to be significantly larger than males: the right postcentral gyrus in the parietal lobe region. Although, on average, males showed larger global WM volume, we did not find any significant difference in global WM volume between males and females.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells

    KAUST Repository

    Ali, Amal J.

    2017-05-03

    Selectins guide the traffic of activated T-cells through the blood stream by mediating their tethering and rolling onto inflamed endothelium, in this way acting as beacons to help navigate them to sites of inflammation. Here, we present a comprehensive analysis of E-selectin ligands expressed on activated human T-cells. We identified several novel glycoproteins that function as E-selectin ligands. Specifically, we compared the role of P-selectin glycoprotein ligand-1 (PSGL-1) and CD43, known E-selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells. We showed that CD44 acts as a functional E-selectin ligand when expressed on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein carries a binding epitope identifying it as hematopoietic cell E- and/or L-selectin ligand (HCELL). Furthermore, by knocking down these ligands individually or together in primary activated human T-cells, we demonstrated that CD44/HCELL, and not CD43, cooperates with PSGL-1 as a major E-selectin ligand. Additionally, we demonstrated the relevance of our findings to chronic autoimmune disease, by showing that CD44/HCELL and PSGL-1, but not CD43, from T-cells isolated from psoriasis patients, bind E-selectin.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Older Adults with Mild Cognitive Impairments Show Less Driving Errors after a Multiple Sessions Simulator Training Program but Do Not Exhibit Long Term Retention.

    Science.gov (United States)

    Teasdale, Normand; Simoneau, Martin; Hudon, Lisa; Germain Robitaille, Mathieu; Moszkowicz, Thierry; Laurendeau, Denis; Bherer, Louis; Duchesne, Simon; Hudon, Carol

    2016-01-01

    The driving performance of individuals with mild cognitive impairment (MCI) is suboptimal when compared to healthy older adults. It is expected that the driving will worsen with the progression of the cognitive decline and thus, whether or not these individuals should continue to drive is a matter of debate. The aim of the study was to provide support to the claim that individuals with MCI can benefit from a training program and improve their overall driving performance in a driving simulator. Fifteen older drivers with MCI participated in five training sessions in a simulator (over a 21-day period) and in a 6-month recall session. During training, they received automated auditory feedback on their performance when an error was noted about various maneuvers known to be suboptimal in MCI individuals (for instance, weaving, omitting to indicate a lane change, to verify a blind spot, or to engage in a visual search before crossing an intersection). The number of errors was compiled for eight different maneuvers for all sessions. For the initial five sessions, a gradual and significant decrease in the number of errors was observed, indicating learning and safer driving. The level of performance, however, was not maintained at the 6-month recall session. Nevertheless, the initial learning observed opens up possibilities to undertake more regular interventions to maintain driving skills and safe driving in MCI individuals.

  5. Feline bone marrow-derived mesenchymal stromal cells (MSCs) show similar phenotype and functions with regards to neuronal differentiation as human MSCs.

    Science.gov (United States)

    Munoz, Jessian L; Greco, Steven J; Patel, Shyam A; Sherman, Lauren S; Bhatt, Suresh; Bhatt, Rekha S; Shrensel, Jeffrey A; Guan, Yan-Zhong; Xie, Guiqin; Ye, Jiang-Hong; Rameshwar, Pranela; Siegel, Allan

    2012-09-01

    Mesenchymal stromal cells (MSCs) show promise for treatment of a variety of neurological and other disorders. Cat has a high degree of linkage with the human genome and has been used as a model for analysis of neurological disorders such as stroke, Alzheimer's disease and motor disorders. The present study was designed to characterize bone marrow-derived MSCs from cats and to investigate the capacity to generate functional peptidergic neurons. MSCs were expanded with cells from the femurs of cats and then characterized by phenotype and function. Phenotypically, feline and human MSCs shared surface markers, and lacked hematopoietic markers, with similar morphology. As compared to a subset of human MSCs, feline MSCs showed no evidence of the major histocompatibility class II. Since the literature suggested Stro-1 as an indicator of pluripotency, we compared early and late passages feline MSCs and found its expression in >90% of the cells. However, the early passage cells showed two distinct populations of Stro-1-expressing cells. At passage 5, the MSCs were more homogeneous with regards to Stro-1 expression. The passage 5 MSCs differentiated to osteogenic and adipogenic cells, and generated neurons with electrophysiological properties. This correlated with the expression of mature neuronal markers with concomitant decrease in stem cell-associated genes. At day 12 induction, the cells were positive for MAP2, Neuronal Nuclei, tubulin βIII, Tau and synaptophysin. This correlated with electrophysiological maturity as presented by excitatory postsynaptic potentials (EPSPs). The findings indicate that the cat may constitute a promising biomedical model for evaluation of novel therapies such as stem cell therapy in such neurological disorders as Alzheimer's disease and stroke. Copyright © 2012 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  6. Dobrava-Belgrade hantavirus from Germany shows receptor usage and innate immunity induction consistent with the pathogenicity of the virus in humans.

    Directory of Open Access Journals (Sweden)

    Elena Popugaeva

    Full Text Available BACKGROUND: Dobrava-Belgrade virus (DOBV is a European hantavirus causing hemorrhagic fever with renal syndrome (HFRS in humans with fatality rates of up to 12%. DOBV-associated clinical cases typically occur also in the northern part of Germany where the virus is carried by the striped field mouse (Apodemus agrarius. However, the causative agent responsible for human illness has not been previously isolated. METHODOLOGY/PRINCIPAL FINDINGS: Here we report on characterization of a novel cell culture isolate from Germany obtained from a lung tissue of "spillover" infected yellow necked mouse (A. flavicollis trapped near the city of Greifswald. Phylogenetic analyses demonstrated close clustering of the new strain, designated Greifswald/Aa (GRW/Aa with the nucleotide sequence obtained from a northern German HFRS patient. The virus was effectively blocked by specific antibodies directed against β3 integrins and Decay Accelerating Factor (DAF indicating that the virus uses same receptors as the highly pathogenic Hantaan virus (HTNV. In addition, activation of selected innate immunity markers as interferon β and λ and antiviral protein MxA after viral infection of A549 cells was investigated and showed that the virus modulates the first-line antiviral response in a similar way as HTNV. CONCLUSIONS/SIGNIFICANCE: In summary, our study reveals novel data on DOBV receptor usage and innate immunity induction in relationship to virus pathogenicity and underlines the potency of German DOBV strains to act as human pathogen.

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

    Science.gov (United States)

    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.

  8. 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...

  9. 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.

  10. 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...

  11. 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.

  12. Plasmid-based generation of induced neural stem cells from adult human fibroblasts

    Directory of Open Access Journals (Sweden)

    Philipp Capetian

    2016-10-01

    Full Text Available Direct reprogramming from somatic to neural cell types has become an alternative to induced pluripotent stem cells. Most protocols employ viral expression systems, posing the risk of random genomic integration. Recent developments led to plasmid-based protocols, lowering this risk. However, these protocols either relied on continuous presence of a variety of small molecules or were only able to reprogram murine cells. We therefore established a reprogramming protocol based on vectors containing the Epstein-Barr virus (EBV-derived oriP/EBNA1 as well as the defined expression factors Oct3/4, Sox2, Klf4, L-myc, Lin28, and a small hairpin directed against p53. We employed a defined neural medium in combination with the neurotrophins bFGF, EGF and FGF4 for cultivation without the addition of small molecules. After reprogramming, cells demonstrated a temporary increase in the expression of endogenous Oct3/4. We obtained induced neural stem cells (iNSC 30 days after transfection. In contrast to previous results, plasmid vectors as well as a residual expression of reprogramming factors remained detectable in all cell lines. Cells showed a robust differentiation into neuronal (72% and glial cells (9% astrocytes, 6% oligodendrocytes. Despite the temporary increase of pluripotency-associated Oct3/4 expression during reprogramming, we did not detect pluripotent stem cells or non-neural cells in culture (except occasional residual fibroblasts. Neurons showed electrical activity and functional glutamatergic synapses. Our results demonstrate that reprogramming adult human fibroblasts to iNSC by plasmid vectors and basic neural medium without small molecules is possible and feasible. However, a full set of pluripotency-associated transcription factors may indeed result in the acquisition of a transient (at least partial pluripotent intermediate during reprogramming. In contrast to previous reports, the EBV-based plasmid system remained present and active inside

  13. Children Do Not Behave Like Adults: Gender Gaps in Performance and Risk Taking within a Random Social Context in the High-StakesGame Shows Jeopardy and Junior Jeopardy

    OpenAIRE

    Säve-Söderbergh, Jenny; Lindquist, Gabriella Sjögren

    2014-01-01

    Using unique panel data, we compare cognitive performance and wagering behavior of children (10-11 years) with adults playing in the Swedish version of the TV-shows Jeopardy and Junior Jeopardy. Although facing the same well-known high-stakes game, and controlling for performance differences, there is no gender gap in risk-taking among girls and boys in contrast with adults, and, while girls take more risk than women, boys take less risk than men. We also find that female behavior is differen...

  14. A human intervention study with foods containing natural Ah-receptor agonists does not significantly show AhR-mediated effects as measured in blood cells and urine.

    Science.gov (United States)

    de Waard, Pim W J; Peijnenburg, Ad A C M; Baykus, Hakan; Aarts, Jac M M J G; Hoogenboom, Ron L A P; van Schooten, Frederik J; de Kok, Theo M C M

    2008-10-22

    Binding and activation of the aryl hydrocarbon receptor (AhR) is thought to be an essential step in the toxicity of the environmental pollutants dioxins and dioxin-like PCBs. However, also a number of natural compounds, referred to as NAhRAs (natural Ah-receptor agonists), which are present in, for example, fruits and vegetables, can bind and activate this receptor. To study their potential effects in humans, we first investigated the effect of the prototypical AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression in ex vivo exposed freshly isolated human lymphocytes, and compared the resulting gene expression profile with those caused by the well-known NAhRA indolo[3,2-b]carbazole (ICZ), originating from cruciferous vegetables, and by a hexane extract of NAhRA-containing grapefruit juice (GJE). Only ICZ induced a gene expression profile similar to TCDD in the lymphocytes, and both significantly up-regulated CYP1B1 and TIPARP (TCDD-inducible poly (ADP-ribose) polymerase) mRNA. Next, we performed a human intervention study with NAhRA-containing cruciferous vegetables and grapefruit juice. The expression of the prototypical AhR-responsive genes CYP1A1, CYP1B1 and NQO1 in whole blood cells and in freshly isolated lymphocytes was not significantly affected. Also enzyme activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO), as judged by caffeine metabolites in urine, were unaffected, except for a small down-regulation of NAT2 activity by grapefruit juice. Examination of blood plasma with DR CALUX showed a 12% increased AhR agonist activity 3 and 24 h after consumption of cruciferous vegetables, but did not show a significant effect of grapefruit juice consumption. We conclude that intake of NAhRAs from food may result in minor AhR-related effects measurable in human blood and urine.

  15. Analysis of S gene mutation of the hepatitis B virus in adult liver transplant recipients showing resistance to hepatitis B immunoglobulin therapy.

    Science.gov (United States)

    Park, G-C; Hwang, S; Ahn, C-S; Kim, K-H; Moon, D-B; Ha, T-Y; Song, G-W; Jung, D-H; Shin, Y W; Kim, S-H; Chang, K-H; Namgoong, J-M; Park, C-S; Park, H-W; Park, Y-H; Kang, S-H; Jung, B-H; Lee, S-G

    2013-10-01

    A considerable proportion of recipients of liver transplantations who are presented hepatitis B immunoglobulin (HBIG) monotherapy for hepatitis B virus (HBV) prophylaxis develop HBIG resistance. In this study, we investigated the mutation patterns in the major hydrophilic region (MHR) of amino acid sequences 100 to 160. Using the gene sequence analyzer for amino acid sequences 0 to 226 in the S/pre-S region we analyzed blood samples of 15 patients showing HBIG resistance after high-dose HBIG prophylaxis. Various mutations in the MHR were observed in 14/15 samples: Gly145Arg mutation in 8/13 Adr subtype and 1/2 Ayw subtype samples (60%). The next most common mutation was Gly165Trp in 8/13 Adr subtype but neither of 2 Ayw subtype samples (53.3%). Concurrent antiviral resistance was noted in 5 patients: lamivudine (n = 5), or entecavir (n = 3), but not adefovir, suggesting the occurrence of simultaneous, antiviral cross-resistances. Two patients underwent retransplantation due to the progression of HBV infection despite vigorous antiviral therapy. At diagnosis of HBV recurrence, the mean HBV DNA load was 6.5 × 10(6) copies/mL; 4 patients showed paradoxical coexistence of anti-HBs and HBsAg. Currently, 2 subjects show low-level HBV DNA replication in peripheral blood, although the other 12 had no DNA replication after prolonged antiviral therapy. This study suggested that various mutations in the "a" determinant were associated with HBIG resistance. Since treatment failure to rescue antiviral therapy was often associated with delayed detection of HBV recurrence rather than concurrent antiviral resistance, frequent HBV surveillance using more sensitive screening tests, such as HBeAg and HBV DNA polymerase chain reaction assay, seems to be mandatory. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. 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

  17. 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

  18. Short-acting insulin analogues versus regular human insulin for adults with type 1 diabetes mellitus.

    Science.gov (United States)

    Fullerton, Birgit; Siebenhofer, Andrea; Jeitler, Klaus; Horvath, Karl; Semlitsch, Thomas; Berghold, Andrea; Plank, Johannes; Pieber, Thomas R; Gerlach, Ferdinand M

    2016-06-30

    Short-acting insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. To assess the effects of short-acting insulin analogues versus regular human insulin in adults with type 1 diabetes. We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared short-acting insulin analogues with regular human insulins in the treatment of adults with type 1 diabetes who were not pregnant. Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in

  19. 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.

  20. When seeing depends on knowing: adults with Autism Spectrum Conditions show diminished top-down processes in the visual perception of degraded faces but not degraded objects.

    Science.gov (United States)

    Loth, Eva; Gómez, Juan Carlos; Happé, Francesca

    2010-04-01

    Behavioural, neuroimaging and neurophysiological approaches emphasise the active and constructive nature of visual perception, determined not solely by the environmental input, but modulated top-down by prior knowledge. For example, degraded images, which at first appear as meaningless 'blobs', can easily be recognized as, say, a face, after having seen the same image un-degraded. This conscious perception of the fragmented stimuli relies on top-down priming influences from systems involved in attention and mental imagery on the processing of stimulus attributes, and feature-binding [Dolan, R. J., Fink, G. R., Rolls, E., Booth, M., Holmes, A., Frackowiak, R. S. J., et al. (1997). How the brain learns to see objects and faces in an impoverished context. Nature, 389, 596-599]. In Autism Spectrum Conditions (ASC), face processing abnormalities are well-established, but top-down anomalies in various domains have also been shown. Thus, we tested two alternative hypotheses: (i) that people with ASC show overall reduced top-down modulation in visual perception, or (ii) that top-down anomalies affect specifically the perception of faces. Participants were presented with sets of three consecutive images: degraded images (of faces or objects), corresponding or non-corresponding grey-scale photographs, and the same degraded images again. In a passive viewing sequence we compared gaze times (an index of focal attention) on faces/objects vs. background before and after viewers had seen the undegraded photographs. In an active viewing sequence, we compared how many faces/objects were identified pre- and post-exposure. Behavioural and gaze tracking data showed significantly reduced effects of prior knowledge on the conscious perception of degraded faces, but not objects in the ASC group. Implications for future work on the underlying mechanisms, at the cognitive and neurofunctional levels, are discussed. (c) 2009 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  2. Human second trimester amniotic fluid cells are able to create embryoid body-like structures in vitro and to show typical expression profiles of embryonic and primordial germ cells.

    Science.gov (United States)

    Antonucci, Ivana; Di Pietro, Roberta; Alfonsi, Melissa; Centurione, Maria Antonietta; Centurione, Lucia; Sancilio, Silvia; Pelagatti, Francesca; D'Amico, Maria Angela; Di Baldassarre, Angela; Piattelli, Adriano; Tetè, Stefano; Palka, Giandomenico; Borlongan, Cesar V; Stuppia, Liborio

    2014-01-01

    Human amniotic fluid-derived stem cells (AFSCs) represent a novel class of broadly multipotent stem cells sharing characteristics of both embryonic and adult stem cells. However, both the origin of these cells and their actual properties in terms of pluripotent differentiation potential are still debated. In order to verify the presence of features of pluripotency in human second trimester AFSCs, we have investigated the ability of these cells to form in vitro three-dimensional aggregates, known as embryoid bodies (EBs), and to express specific genes of embryonic stem cells (ESCs) and primordial germ cells (PGCs). EBs were obtained after 5 days of AFSC culture in suspension and showed positivity for alkaline phosphatase (AP) staining and for specific markers of pluripotency (OCT4 and SOX2). Moreover, EB-derived cells showed the expression of specific transcripts of the three germ layers. RT-PCR analysis, carried out at different culture times (second, third, fourth, fifth, and eighth passages), revealed the presence of specific markers of ESCs (such as FGF4 and DAPPA4), as well as of markers typical of PGCs and, in particular, genes involved in early stages of germ cell development (Fragilis, Stella, Vasa, c-Kit, Rnf17). Finally, the expression of genes related to the control of DNA methylation (DNMT3A, DNMT3b1, DNMT1, DNMT3L, MBD1, MBD2, MBD3, MDB4, MeCP2), as well as the lack of inactivation of the X-chromosome in female samples, was also demonstrated. Taken together, these data provide further evidence for the presence of common features among human AFSCs, PGCs, and ESCs.

  3. Immature dendritic cells generated from cryopreserved human monocytes show impaired ability to respond to LPS and to induce allogeneic lymphocyte proliferation.

    Directory of Open Access Journals (Sweden)

    Guilherme Ferreira Silveira

    Full Text Available Dendritic cells play a key role in the immune system, in the sensing of foreign antigens and triggering of an adaptive immune response. Cryopreservation of human monocytes was investigated to understand its effect on differentiation into immature monocyte-derived dendritic cells (imdDCs, the response to inflammatory stimuli and the ability to induce allogeneic lymphocyte proliferation. Cryopreserved (crp-monocytes were able to differentiate into imdDCs, albeit to a lesser extent than freshly (frh-obtained monocytes. Furthermore, crp-imdDCs had lower rates of maturation and cytokine/chemokine secretion in response to LPS than frh-imdDCs. Lower expression of Toll-like receptor 4 (at 24 and 48 h and higher susceptibility to apoptosis in crp-imdDCs than in fresh cells would account for the impaired maturation and cytokine/chemokine secretion observed. A mixed leukocyte reaction showed that lymphocyte proliferation was lower with crp-imdDCs than with frh-imdDCs. These findings suggested that the source of monocytes used to generate human imdDCs could influence the accuracy of results observed in studies of the immune response to pathogens, lymphocyte activation, vaccination and antigen sensing. It is not always possible to work with freshly isolated monocytes but the possible effects of freezing/thawing on the biology and responsiveness of imdDCs should be taken into account.

  4. Inactivated ORF virus shows antifibrotic activity and inhibits human hepatitis B virus (HBV) and hepatitis C virus (HCV) replication in preclinical models.

    Science.gov (United States)

    Paulsen, Daniela; Urban, Andreas; Knorr, Andreas; Hirth-Dietrich, Claudia; Siegling, Angela; Volk, Hans-Dieter; Mercer, Andrew A; Limmer, Andreas; Schumak, Beatrix; Knolle, Percy; Ruebsamen-Schaeff, Helga; Weber, Olaf

    2013-01-01

    Inactivated orf virus (iORFV), strain D1701, is a potent immune modulator in various animal species. We recently demonstrated that iORFV induces strong antiviral activity in animal models of acute and chronic viral infections. In addition, we found D1701-mediated antifibrotic effects in different rat models of liver fibrosis. In the present study, we compare iORFV derived from two different strains of ORFV, D1701 and NZ2, respectively, with respect to their antifibrotic potential as well as their potential to induce an antiviral response controlling infections with the hepatotropic pathogens hepatitis C virus (HCV) and hepatitis B virus (HBV). Both strains of ORFV showed anti-viral activity against HCV in vitro and against HBV in a transgenic mouse model without signs of necro-inflammation in vivo. Our experiments suggest that the absence of liver damage is potentially mediated by iORFV-induced downregulation of antigen cross-presentation in liver sinus endothelial cells. Furthermore, both strains showed significant anti-fibrotic activity in rat models of liver fibrosis. iORFV strain NZ2 appeared more potent compared to strain D1701 with respect to both its antiviral and antifibrotic activity on the basis of dosages estimated by titration of active virus. These results show a potential therapeutic approach against two important human liver pathogens HBV and HCV that independently addresses concomitant liver fibrosis. Further studies are required to characterize the details of the mechanisms involved in this novel therapeutic principle.

  5. Inactivated ORF virus shows antifibrotic activity and inhibits human hepatitis B virus (HBV and hepatitis C virus (HCV replication in preclinical models.

    Directory of Open Access Journals (Sweden)

    Daniela Paulsen

    Full Text Available Inactivated orf virus (iORFV, strain D1701, is a potent immune modulator in various animal species. We recently demonstrated that iORFV induces strong antiviral activity in animal models of acute and chronic viral infections. In addition, we found D1701-mediated antifibrotic effects in different rat models of liver fibrosis. In the present study, we compare iORFV derived from two different strains of ORFV, D1701 and NZ2, respectively, with respect to their antifibrotic potential as well as their potential to induce an antiviral response controlling infections with the hepatotropic pathogens hepatitis C virus (HCV and hepatitis B virus (HBV. Both strains of ORFV showed anti-viral activity against HCV in vitro and against HBV in a transgenic mouse model without signs of necro-inflammation in vivo. Our experiments suggest that the absence of liver damage is potentially mediated by iORFV-induced downregulation of antigen cross-presentation in liver sinus endothelial cells. Furthermore, both strains showed significant anti-fibrotic activity in rat models of liver fibrosis. iORFV strain NZ2 appeared more potent compared to strain D1701 with respect to both its antiviral and antifibrotic activity on the basis of dosages estimated by titration of active virus. These results show a potential therapeutic approach against two important human liver pathogens HBV and HCV that independently addresses concomitant liver fibrosis. Further studies are required to characterize the details of the mechanisms involved in this novel therapeutic principle.

  6. Gastrointestinal Simulation Model TWIN-SHIME Shows Differences between Human Urolithin-Metabotypes in Gut Microbiota Composition, Pomegranate Polyphenol Metabolism, and Transport along the Intestinal Tract.

    Science.gov (United States)

    García-Villalba, Rocío; Vissenaekens, Hanne; Pitart, Judit; Romo-Vaquero, María; Espín, Juan C; Grootaert, Charlotte; Selma, María V; Raes, Katleen; Smagghe, Guy; Possemiers, Sam; Van Camp, John; Tomas-Barberan, Francisco A

    2017-07-12

    A TWIN-SHIME system was used to compare the metabolism of pomegranate polyphenols by the gut microbiota from two individuals with different urolithin metabotypes. Gut microbiota, ellagitannin metabolism, short-chain fatty acids (SCFA), transport of metabolites, and phase II metabolism using Caco-2 cells were explored. The simulation reproduced the in vivo metabolic profiles for each metabotype. The study shows for the first time that microbial composition, metabolism of ellagitannins, and SCFA differ between metabotypes and along the large intestine. The assay also showed that pomegranate phenolics preserved intestinal cell integrity. Pomegranate polyphenols enhanced urolithin and propionate production, as well as Akkermansia and Gordonibacter prevalence with the highest effect in the descending colon. The system provides an insight into the mechanisms of pomegranate polyphenol gut microbiota metabolism and absorption through intestinal cells. The results obtained by the combined SHIME/Caco-2 cell system are consistent with previous human and animal studies and show that although urolithin metabolites are present along the gastrointestinal tract due to enterohepatic circulation, they are predominantly produced in the distal colon region.

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

    NARCIS (Netherlands)

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

    2014-01-01

    textabstractUsing 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

  8. Using "The Simpsons" to Teach Humanities with Gen X and Gen Y Adult Students

    Science.gov (United States)

    Fink, Maxwell A.; Foote, Deborah C.

    2007-01-01

    Many educators lament the UNESCO study showing that by the time the average teen graduates from high school he or she has spent more than fifteen thousand hours watching television and only eleven thousand in the classroom (Gorebel, 1998). Rather than regretting this "condition," colleges, universities, and educators of adults and children should…

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

    NARCIS (Netherlands)

    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.; McCarty, Catherine A.; Starren, Justin; Peissig, Peggy; Berg, Richard; Rasmussen, Luke; Linneman, James; Miller, Aaron; Choudary, Vidhu; Chen, Lin; Waudby, Carol; Kitchner, Terrie; Reeser, Jonathan; Fost, Norman; Wilke, Russell A.; Chisholm, Rex L.; Avila, Pedro C.; Greenland, Philip; Hayes, M. Geoff; Kho, Abel; Kibbe, Warren A.; Lemke, Amy A.; Lowe, William L.; Smith, Maureen E.; Wolf, Wendy A.; Pacheco, Jennifer A.; Thompson, William K.; Humowiecki, Joel; Law, May; Chute, Christopher; Kullo, Iftikar; Koenig, Barbara; de Andrade, Mariza; Bielinski, Suzette; Pathak, Jyotishman; Savova, Guergana; Wu, Joel; Henriksen, Joan; Ding, Keyue; Hart, Lacey; Palbicki, Jeremy; Larson, Eric B.; Newton, Katherine; Ludman, Evette; Spangler, Leslie; Hart, Gene; Carrell, David; Jarvik, Gail; Crane, Paul; Burke, Wylie; Fullerton, Stephanie Malia; Trinidad, Susan Brown; Carlson, Chris; Hutchinson, Fred; McDavid, Andrew; Roden, Dan M.; Clayton, Ellen; Haines, Jonathan L.; Masys, Daniel R.; Churchill, Larry R.; Cornfield, Daniel; Crawford, Dana; Darbar, Dawood; Denny, Joshua C.; Malin, Bradley A.; Ritchie, Marylyn D.; Schildcrout, Jonathan S.; Xu, Hua; Ramirez, Andrea Havens; Basford, Melissa; Pulley, Jill; Alizadeh, Behrooz Z.; de Boer, Rudolf A.; Boezen, H. Marike; van der Klauw, Melanie M.; Navis, Gerjan; Ormel, Johan; Postma, Dirkje S.; Rosmalen, Judith G. M.; Slaets, Joris P.; Wolffenbuttel, Bruce H. R.; Wijmenga, Cisca; Kathiresan, Sekar; Voight, Benjamin F.; Purcell, Shaun; Musunuru, Kiran; Ardissino, Diego; Mannucci, Pier M.; Anand, Sonia; Engert, James C.; Reilly, Muredach P.; Rader, Daniel J.; Morgan, Thomas; Spertus, John A.; Stoll, Monika; Girelli, Domenico; McKeown, Pascal P.; Patterson, Chris C.; Siscovick, David S.; O'Donnell, Christopher J.; Elosua, Roberto; Peltonen, Leena; Schwartz, Stephen M.; Melander, Olle; Altshuler, David; Merlini, Pier Angelica; Berzuini, Carlo; Bernardinelli, Luisa; Peyvandi, Flora; Tubaro, Marco; Celli, Patrizia; Ferrario, Maurizio; Fetiveau, Raffaela; Marziliano, Nicola; Casari, Giorgio; Galli, Michele; Ribichini, Flavio; Rossi, Marco; Bernardi, Francesco; Zonzin, Pietro; Piazza, Alberto; Yee, Jean; Friedlander, Yechiel; Marrugat, Jaume; Lucas, Gavin; Subirana, Isaac; Sala, Joan; Ramos, Rafael; Meigs, James B.; Williams, Gordon; Nathan, David M.; MacRae, Calum A.; Havulinna, Aki S.; Berglund, Goran; Asselta, Rosanna; Duga, Stefano; Spreafico, Marta; Daly, Mark J.; Nemesh, James; Korn, Joshua M.; McCarroll, Steven A.; Surti, Aarti; Guiducci, Candace; Gianniny, Lauren; Mirel, Daniel; Parkin, Melissa; Burtt, Noel; Gabriel, Stacey B.; Thompson, John R.; Braund, Peter S.; Wright, Benjamin J.; Balmforth, Anthony J.; Ball, Stephen G.; Schunkert, I. Heribert; Linsel-Nitschke, Patrick; Lieb, Wolfgang; Ziegler, Andreas; König, Inke R.; Fischer, Marcus; Stark, Klaus; Grosshennig, Anika; Preuss, Michael; Schreiber, Stefan; Ouwehand, Willem; Scholz, Michael; Cambien, Francois; Goodall, Alison; Li, Mingyao; Chen, Zhen; Wilensky, Robert; Matthai, William; Qasim, Atif; Hakonarson, Hakon H.; Devaney, Joe; Burnett, Mary-Susan; Pichard, Augusto D.; Kent, Kenneth M.; Satler, Lowell; Lindsay, Joseph M.; Waksman, Ron; Knouff, Christopher W.; Waterworth, Dawn M.; Walker, Max C.; Mooser, Vincent; Epstein, Stephen E.; Scheffold, Thomas; Berger, Klaus; Huge, Andreas; Martinelli, Nicola; Olivieri, Oliviero; Corrocher, Roberto; Hólm, Hilma; Do, Ron; Xie, Changchun; Siscovick, David; Matise, Tara; Buyske, Steve; Higashio, Julia; Williams, Rasheeda; Nato, Andrew; Ambite, Jose Luis; Deelman, Ewa; Manolio, Teri; Hindorff, Lucia; Heiss, Gerardo; Taylor, Kira; Franceschini, Nora; Avery, Christy; Graff, Misa; Lin, Danyu; Quibrera, Miguel; Cochran, Barbara; Kao, Linda; Umans, Jason; Cole, Shelley; MacCluer, Jean; Person, Sharina; Pankow, James; Gross, Myron; Fornage, Myriam; Durda, Peter; Jenny, Nancy; Patsy, Bruce; Arnold, Alice; Buzkova, Petra; Haines, Jonathan; Murdock, Deborah; Glenn, Kim; Brown-Gentry, Kristin; Thornton-Wells, Tricia; Dumitrescu, Logan; Bush, William S.; Mitchell, Sabrina L.; Goodloe, Robert; Wilson, Sarah; Boston, Jonathan; Malinowski, Jennifer; Restrepo, Nicole; Oetjens, Matthew; Fowke, Jay; Zheng, Wei; Spencer, Kylee; Pendergrass, Sarah; Le Marchand, Loïc; Wilkens, Lynne; Park, Lani; Tiirikainen, Maarit; Kolonel, Laurence; Cheng, Iona; Wang, Hansong; Shohet, Ralph; Haiman, Christopher; Stram, Daniel; Henderson, Brian; Monroe, Kristine; Schumacher, Fredrick; Anderson, Garnet; Prentice, Ross; LaCroix, Andrea; Wu, Chunyuan; Carty, Cara; Rosse, Stephanie; Young, Alicia; Haessler, Jeff; Kocarnik, Jonathan; Lin, Yi; Jackson, Rebecca; Duggan, David; Kuller, Lew

    2014-01-01

    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

  10. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

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

    Science.gov (United States)

    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.

  17. Ectopic Human Fasciola hepatica Infection by an Adult Worm in the Mesocolon.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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/.

  19. Fatty acid oxidation in the human fetus: implications for fetal and adult disease

    NARCIS (Netherlands)

    Oey, Nadia A.; Ruiter, Jos P. N.; Attié-Bitach, Tania; Ijlst, Lodewijk; Wanders, Ronald J. A.; Wijburg, Frits A.

    2006-01-01

    Studies in the last few years have shown a remarkably high activity of fatty acid oxidation (FAO) enzymes in human placenta. We have recently shown mRNA expression as well as enzymatic activity of long-chain FAO enzymes in the human embryo and fetus. In this study we show activity of the FAO enzymes

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  5. Direct Reprogramming of Adult Human Somatic Stem Cells Into Functional Neurons Using Sox2, Ascl1, and Neurog2

    Directory of Open Access Journals (Sweden)

    Jessica Alves de Medeiros Araújo

    2018-06-01

    Full Text Available Reprogramming of somatic cells into induced pluripotent stem cells (iPS or directly into cells from a different lineage, including neurons, has revolutionized research in regenerative medicine in recent years. Mesenchymal stem cells are good candidates for lineage reprogramming and autologous transplantation, since they can be easily isolated from accessible sources in adult humans, such as bone marrow and dental tissues. Here, we demonstrate that expression of the transcription factors (TFs SRY (sex determining region Y-box 2 (Sox2, Mammalian achaete-scute homolog 1 (Ascl1, or Neurogenin 2 (Neurog2 is sufficient for reprogramming human umbilical cord mesenchymal stem cells (hUCMSC into induced neurons (iNs. Furthermore, the combination of Sox2/Ascl1 or Sox2/Neurog2 is sufficient to reprogram up to 50% of transfected hUCMSCs into iNs showing electrical properties of mature neurons and establishing synaptic contacts with co-culture primary neurons. Finally, we show evidence supporting the notion that different combinations of TFs (Sox2/Ascl1 and Sox2/Neurog2 may induce multiple and overlapping neuronal phenotypes in lineage-reprogrammed iNs, suggesting that neuronal fate is determined by a combination of signals involving the TFs used for reprogramming but also the internal state of the converted cell. Altogether, the data presented here contribute to the advancement of techniques aiming at obtaining specific neuronal phenotypes from lineage-converted human somatic cells to treat neurological disorders.

  6. Expression pattern of thymosin beta 4 in the adult human liver

    Directory of Open Access Journals (Sweden)

    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.

  7. 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...

  8. Neurons from the adult human dentate nucleus: neural networks in the neuron classification.

    Science.gov (United States)

    Grbatinić, Ivan; Marić, Dušica L; Milošević, Nebojša T

    2015-04-07

    Topological (central vs. border neuron type) and morphological classification of adult human dentate nucleus neurons according to their quantified histomorphological properties using neural networks on real and virtual neuron samples. In the real sample 53.1% and 14.1% of central and border neurons, respectively, are classified correctly with total of 32.8% of misclassified neurons. The most important result present 62.2% of misclassified neurons in border neurons group which is even greater than number of correctly classified neurons (37.8%) in that group, showing obvious failure of network to classify neurons correctly based on computational parameters used in our study. On the virtual sample 97.3% of misclassified neurons in border neurons group which is much greater than number of correctly classified neurons (2.7%) in that group, again confirms obvious failure of network to classify neurons correctly. Statistical analysis shows that there is no statistically significant difference in between central and border neurons for each measured parameter (p>0.05). Total of 96.74% neurons are morphologically classified correctly by neural networks and each one belongs to one of the four histomorphological types: (a) neurons with small soma and short dendrites, (b) neurons with small soma and long dendrites, (c) neuron with large soma and short dendrites, (d) neurons with large soma and long dendrites. Statistical analysis supports these results (pneurons can be classified in four neuron types according to their quantitative histomorphological properties. These neuron types consist of two neuron sets, small and large ones with respect to their perykarions with subtypes differing in dendrite length i.e. neurons with short vs. long dendrites. Besides confirmation of neuron classification on small and large ones, already shown in literature, we found two new subtypes i.e. neurons with small soma and long dendrites and with large soma and short dendrites. These neurons are

  9. 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...

  10. 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...

  11. 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...

  12. Millennial-scale isotope records from a wide-ranging predator show evidence of recent human impact to oceanic food webs

    DEFF Research Database (Denmark)

    Wiley, A.E.; Ostrom, P.H.; Welch, A.J.

    2013-01-01

    Human exploitation of marine ecosystems is more recent in oceanic than near shore regions, yet our understanding of human impacts on oceanic food webs is comparatively poor. Few records of species that live beyond the continental shelves date back more than 60 y, and the sheer size of oceanic reg...

  13. Probabilistic analysis showing that a combination of bacteroides and methanobrevibacter source tracking markers is effective for identifying waters contaminated by human fecal pollution

    Science.gov (United States)

    Johnston, Christopher; Byappanahalli, Muruleedhara N.; Gibson, Jacqueline MacDonald; Ufnar, Jennifer A.; Whitman, Richard L.; Stewart, Jill R.

    2013-01-01

    Microbial source tracking assays to identify sources of waterborne contamination typically target genetic markers of host-specific microorganisms. However, no bacterial marker has been shown to be 100% host-specific, and cross-reactivity has been noted in studies evaluating known source samples. Using 485 challenge samples from 20 different human and animal fecal sources, this study evaluated microbial source tracking markers including the Bacteroides HF183 16S rRNA, M. smithii nifH, and Enterococcus esp gene targets that have been proposed as potential indicators of human fecal contamination. Bayes' Theorem was used to calculate the conditional probability that these markers or a combination of markers can correctly identify human sources of fecal pollution. All three human-associated markers were detected in 100% of the sewage samples analyzed. Bacteroides HF183 was the most effective marker for determining whether contamination was specifically from a human source, and greater than 98% certainty that contamination was from a human source was shown when both Bacteroides HF183 and M. smithii nifH markers were present. A high degree of certainty was attained even in cases where the prior probability of human fecal contamination was as low as 8.5%. The combination of Bacteroides HF183 and M. smithii nifH source tracking markers can help identify surface waters impacted by human fecal contamination, information useful for prioritizing restoration activities or assessing health risks from exposure to contaminated waters.

  14. A simple method for analyzing exome sequencing data shows distinct levels of nonsynonymous variation for human immune and nervous system genes.

    Directory of Open Access Journals (Sweden)

    Jan Freudenberg

    Full Text Available To measure the strength of natural selection that acts upon single nucleotide variants (SNVs in a set of human genes, we calculate the ratio between nonsynonymous SNVs (nsSNVs per nonsynonymous site and synonymous SNVs (sSNVs per synonymous site. We transform this ratio with a respective factor f that corrects for the bias of synonymous sites towards transitions in the genetic code and different mutation rates for transitions and transversions. This method approximates the relative density of nsSNVs (rdnsv in comparison with the neutral expectation as inferred from the density of sSNVs. Using SNVs from a diploid genome and 200 exomes, we apply our method to immune system genes (ISGs, nervous system genes (NSGs, randomly sampled genes (RSGs, and gene ontology annotated genes. The estimate of rdnsv in an individual exome is around 20% for NSGs and 30-40% for ISGs and RSGs. This smaller rdnsv of NSGs indicates overall stronger purifying selection. To quantify the relative shift of nsSNVs towards rare variants, we next fit a linear regression model to the estimates of rdnsv over different SNV allele frequency bins. The obtained regression models show a negative slope for NSGs, ISGs and RSGs, supporting an influence of purifying selection on the frequency spectrum of segregating nsSNVs. The y-intercept of the model predicts rdnsv for an allele frequency close to 0. This parameter can be interpreted as the proportion of nonsynonymous sites where mutations are tolerated to segregate with an allele frequency notably greater than 0 in the population, given the performed normalization of the observed nsSNV to sSNV ratio. A smaller y-intercept is displayed by NSGs, indicating more nonsynonymous sites under strong negative selection. This predicts more monogenically inherited or de-novo mutation diseases that affect the nervous system.

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

    DEFF Research Database (Denmark)

    Li, Hongzhe; Ghazanfari, Roshanak; Zacharaki, Dimitra

    2014-01-01

    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...... exhibited high levels of genes associated with mesenchymal lineages and HSC supportive function. Moreover, lin(-)/CD45(-)/CD271(+)/CD140a(low/-) cells effectively mediated the ex vivo expansion of transplantable CD34(+) hematopoietic stem cells. Taken together, these data indicate that CD140a is a key...... 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...

  16. Show us you are real: the effect of human-versus-organizational presence on online relationship building through social networking sites.

    Science.gov (United States)

    Park, Hyojung; Lee, Hyunmin

    2013-04-01

    This study examined how creating a human presence in organizational online communication affects organization-public relationships and publics' favorable behavioral intentions to engage in word-of-mouth (WOM) and dialogic communications. Four hypotheses were tested in the context of Twitter through a 2×2 (presence: human vs. organizational×organization type: nonprofit vs. for-profit) within-subjects design. The results revealed that conversational human voice was perceived to be higher for Twitter pages of organizations with a human presence than for those with an organizational presence. Providing a human presence on social media through the use of social media managers' avatars and names appeared to promote favorable organization-public relationships and positive WOM communication. However, dialogic communication intentions did not significantly differ between organizations incorporating a human presence versus an organizational presence into their Twitter pages. The proposed dynamic role of human presence versus organizational presence adds a new perspective as to how organizations can take better advantage of interpersonal aspects of social media.

  17. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Research Advances. Image Pinpoints All 5 Million Atoms in Viral Coat; Bilirubin, "Animals-Only" Pigment, Found in Plants; New Evidence Shows Humans Make Salicylic Acid

    Science.gov (United States)

    King, Angela G.

    2009-08-01

    Recent "firsts" in chemical research: image of a viral capsid pinpointing 5 million atoms; isolation and identification of an "animal" pigment, bilirubin, from a plant source; evidence that humans make salicylic acid.

  20. The Duffy binding protein (PkDBPαII) of Plasmodium knowlesi from Peninsular Malaysia and Malaysian Borneo show different binding activity level to human erythrocytes.

    Science.gov (United States)

    Lim, Khai Lone; Amir, Amirah; Lau, Yee Ling; Fong, Mun Yik

    2017-08-11

    The zoonotic Plasmodium knowlesi is a major cause of human malaria in Malaysia. This parasite uses the Duffy binding protein (PkDBPαII) to interact with the Duffy antigen receptor for chemokines (DARC) receptor on human and macaque erythrocytes to initiate invasion. Previous studies on P. knowlesi have reported distinct Peninsular Malaysia and Malaysian Borneo PkDBPαII haplotypes. In the present study, the differential binding activity of these haplotypes with human and macaque (Macaca fascicularis) erythrocytes was investigated. The PkDBPαII of Peninsular Malaysia and Malaysian Borneo were expressed on the surface of COS-7 cells and tested with human and monkey erythrocytes, with and without anti-Fy6 (anti-Duffy) monoclonal antibody treatment. Binding activity level was determined by counting the number of rosettes formed between the transfected COS-7 cells and the erythrocytes. Anti-Fy6 treatment was shown to completely block the binding of human erythrocytes with the transfected COS-7 cells, thus verifying the specific binding of human DARC with PkDBPαII. Interestingly, the PkDBPαII of Peninsular Malaysia displayed a higher binding activity with human erythrocytes when compared with the Malaysian Borneo PkDBPαII haplotype (mean number of rosettes formed = 156.89 ± 6.62 and 46.00 ± 3.57, respectively; P < 0.0001). However, no difference in binding activity level was seen in the binding assay using M. fascicularis erythrocytes. This study is the first report of phenotypic difference between PkDBPαII haplotypes. The biological implication of this finding is yet to be determined. Therefore, further studies need to be carried out to determine whether this differential binding level can be associated with severity of knowlesi malaria in human.

  1. Cytoskeleton and pericellular matrix organization of pure adult human keratinocytes cultured from suction-blister roof epidermis.

    Science.gov (United States)

    Kariniemi, A L; Lehto, V P; Vartio, T; Virtanen, I

    1982-12-01

    Pure adult human keratinocyte cultures were raised from suction-blister roof epidermis and cultured in MCDB-151 medium. In primary culture the epidermal cells rapidly adhered, spread and began to proliferate on collagen-coated growth substrata but not on uncoated plastic or glass substrata. A fibrillar keratin-specific fluorescence, showing a typical cell-cell arrangement, was seen in all cells in indirect immunofluorescence microscopy, whereas only some cells also showed vimentin-specific staining. A fine fibrillar fibronectin-specific surface staining was seen at the margin of attaching cells and in marginal cells of spreading cell islands, whereas no fluorescence could be seen in epidermal cells, with antibodies against type IV collagen or laminin. Interestingly, the marginal cells also showed intracellular fibronectin. The synthesis of fibronectin in epidermal cell cultures could also be revealed by metabolic labelling experiments with [35S]methionine. In contrast to primary cultures, subcultivated keratinocytes also adhered to uncoated plastic and glass substrata. After subcultivation, keratin and surface fibronectin distribution remained unaltered but after some subcultivations, most of the cells also showed fibrillar vimentin and expressed fibronectin intracellularly. The results show that the suction-blister method provides an easy way to obtain pure epidermal cell cultures without contaminating mesenchymal cells. Our results also suggest a direct role for fibronectin but not for collagen type IV or laminin in adhesion and spreading of epidermal cells in vitro.

  2. Telomere erosion varies during in vitro aging of normal human fibroblasts from young and adult donors.

    Science.gov (United States)

    Figueroa, R; Lindenmaier, H; Hergenhahn, M; Nielsen, K V; Boukamp, P

    2000-06-01

    The life span of normal fibroblasts in vitro (Hayflick limit) depends on donor age, and telomere shortening has been proposed as a potential mechanism. By quantitative fluorescence in situ hybridization and Southern blot analysis, we show progressive telomere loss to about 5 kb mean telomere restriction fragment length in fibroblasts from two adult donors within 40 population doublings, whereas in fibroblasts from two infant donors, telomere erosion is reduced, leaving a mean telomere restriction fragment length of approximately 7 kb at senescence (after approximately 60 population doublings). Aging of fibroblasts from both infant and adult donors was not accompanied by chromosomal abnormalities but was correlated with increased telomere repeat-binding factor 2 expression at both the protein and transcriptional level.

  3. Suicidal ideation and suicide attempts among human immunodeficiency virus-infected adults: differences in risk factors and their implications.

    Science.gov (United States)

    Kang, Cho Ryok; Bang, Ji Hwan; Cho, Sung-Il; Kim, Kui Nam; Lee, Hee-Jin; Ryu, Bo Yeong; Cho, Soo Kyung; Lee, Young Hwa; Oh, Myoung-Don; Lee, Jong-Koo

    2016-01-01

    Many studies have investigated risk factors for suicidal ideation and suicide attempt; however, most have failed to show differences in risk factors between suicidal ideation and suicide attempt among the human immunodeficiency virus (HIV)-infected population. This study was designed to identify differences in risk factors between suicidal ideation and suicide attempts among HIV-infected adults in Seoul. A face-to-face survey of 457 HIV-infected adults was conducted by the Seoul Metropolitan Government in 2013. Multivariate logistic regression analysis was used to identify factors associated with suicidal ideation and suicide attempt. Among 422 participants, 44% had suicidal ideation, and 11% had suicide attempts. The independent risk factors for suicidal ideation were young and middle age, living with someone, history of AIDS-defining opportunistic disease, history of treatment for depression, lower social support, and psychological status. Beneficiaries of National Medical Aid, economic barriers to treatment, history of treatment for depression, and lower psychological status were independently associated with suicide attempts. Patients with HIV in Korea were treated without cost in some centers. Thus, experiencing an economic barrier to treatment might be due in part to ignorance of HIV care policies. Our findings indicate that suicide attempts are associated with socioeconomic factors and information inequality regarding medical care. In conclusion, suicidal ideation closely associated with the psychosocial factors, whereas suicide attempt demonstrates a stronger association with socioeconomic factors. Suicide prevention measures should be implemented to provide information to help HIV-infected patients.

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

    Science.gov (United States)

    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.

  5. Oldest human occupation of Wallacea at Laili Cave, Timor-Leste, shows broad-spectrum foraging responses to late Pleistocene environments

    Science.gov (United States)

    Hawkins, Stuart; O'Connor, Sue; Maloney, Tim Ryan; Litster, Mirani; Kealy, Shimona; Fenner, Jack N.; Aplin, Ken; Boulanger, Clara; Brockwell, Sally; Willan, Richard; Piotto, Elena; Louys, Julien

    2017-09-01

    The Wallacea Archipelago provides an extraordinary laboratory for the study of human colonisation and adaptation, yet few detailed archaeological studies have been conducted in the region that span the earliest phase of human settlement. Laili Cave, in northern Timor-Leste, preserves the oldest human occupation in this insular region with a cultural sequence spanning 11,200 to 44,600 cal BP. Small-bodied vertebrates and invertebrates were recovered to the lowest excavated levels, associated with highly concentrated stone artefacts. We report on human behavioural adaptations within the context of Pleistocene environments and changing landscapes using zooarchaeological, stone artefact, bathymetric, and experimental isotopic analyses. Results indicate that Pleistocene humans used the abundant local chert liberally and engaged in mobile broad-spectrum exploitation of invertebrates and fishes from marine, estuarine, and freshwater environments within close proximity of Laili Cave. The faunal assemblage indicates heterogeneous but relatively stable environments during the late Pleistocene. Variability in subsistence strategies over time appears to be a response to changing landscapes and concomitant local resources. This record contrasts with marine specialisations evident from other sites in Timor-Leste and within the broader Wallacean region.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. Human papilloma virus specific T cells infiltrating cervical cancer and draining lymph nodes show remarkably frequent use of HLA-DQ and -DP as a restriction element

    NARCIS (Netherlands)

    Piersma, Sytse J.; Welters, Marij J. P.; van der Hulst, Jeanette M.; Kloth, Judith N.; Kwappenberg, Kitty M. C.; Trimbos, Baptist J.; Melief, Cornelis J. M.; Hellebrekers, Bart W.; Fleuren, Gert Jan; Kenter, Gemma G.; Offringa, Rienk; van der Burg, Sjoerd H.

    2008-01-01

    Human papillomavirus (HPV)-induced malignancies are frequently infiltrated by lymphocytes. To comprehend the contribution of HPV-specific T cells in this anti-tumor response we developed a method that allowed the analysis of the presence and specificity of cervix-infiltrating and draining lymph node

  12. Bat lung epithelial cells show greater host species-specific innate resistance than MDCK cells to human and avian influenza viruses.

    Science.gov (United States)

    Slater, Tessa; Eckerle, Isabella; Chang, Kin-Chow

    2018-04-10

    With the recent discovery of novel H17N10 and H18N11 influenza viral RNA in bats and report on high frequency of avian H9 seroconversion in a species of free ranging bats, an important issue to address is the extent bats are susceptible to conventional avian and human influenza A viruses. To this end, three bat species (Eidolon helvum, Carollia perspicillata and Tadarida brasiliensis) of lung epithelial cells were separately infected with two avian and two human influenza viruses to determine their relative host innate immune resistance to infection. All three species of bat cells were more resistant than positive control Madin-Darby canine kidney (MDCK) cells to all four influenza viruses. TB1-Lu cells lacked sialic acid α2,6-Gal receptors and were most resistant among the three bat species. Interestingly, avian viruses were relatively more replication permissive in all three bat species of cells than with the use of human viruses which suggest that bats could potentially play a role in the ecology of avian influenza viruses. Chemical inhibition of the JAK-STAT pathway in bat cells had no effect on virus production suggesting that type I interferon signalling is not a major factor in resisting influenza virus infection. Although all three species of bat cells are relatively more resistant to influenza virus infection than control MDCK cells, they are more permissive to avian than human viruses which suggest that bats could have a contributory role in the ecology of avian influenza viruses.

  13. Proteolytic processing of anti-Müllerian hormone differs between human fetal testes and adult ovaries

    DEFF Research Database (Denmark)

    Mamsen, L S; Petersen, T S; Jeppesen, J V

    2015-01-01

    and specificity of a panel of five novel high-affinity AMH monoclonal antibodies. Two recognize the mature C-terminal form of AMH, whereas three recognize the active pro-mature form of AMH in human tissue. The antibodies were tested on fetal male testicular and mesonephric tissue aged 8-19 weeks post conception...... (pc), fetal male serum aged 16-26 weeks pc and human immature GCs by immunofluorescence, immunohistochemistry, ELISA and western blotting. The active pro-mature forms of AMH were expressed in both Sertoli cells from human fetal testis and human immature GCs. In contrast, the mature C-terminal form...... of AMH was hardly detected in Sertoli cells, but was readily detected in GCs. This particular form was also located to the nucleus in GCs, whereas the other investigated AMH forms remained in the cytoplasm. Interestingly, the distribution of the AMH forms in the fetal serum of boys showed...

  14. Domestic sheep show average Coxiella burnetii seropositivity generations after a sheep-associated human Q fever outbreak and lack detectable shedding by placental, vaginal, and fecal routes

    Science.gov (United States)

    Oliveira, Ryan D.; Mousel, Michelle R.; Pabilonia, Kristy L.; Highland, Margaret A.; Taylor, J. Bret; Knowles, Donald P.

    2017-01-01

    Coxiella burnetii is a globally distributed zoonotic bacterial pathogen that causes abortions in ruminant livestock. In humans, an influenza-like illness results with the potential for hospitalization, chronic infection, abortion, and fatal endocarditis. Ruminant livestock, particularly small ruminants, are hypothesized to be the primary transmission source to humans. A recent Netherlands outbreak from 2007–2010 traced to dairy goats resulted in over 4,100 human cases with estimated costs of more than 300 million euros. Smaller human Q fever outbreaks of small ruminant origin have occurred in the United States, and characterizing shedding is important to understand the risk of future outbreaks. In this study, we assessed bacterial shedding and seroprevalence in 100 sheep from an Idaho location associated with a 1984 human Q fever outbreak. We observed 5% seropositivity, which was not significantly different from the national average of 2.7% for the U.S. (P>0.05). Furthermore, C. burnetii was not detected by quantitative PCR from placentas, vaginal swabs, or fecal samples. Specifically, a three-target quantitative PCR of placenta identified 0.0% shedding (exact 95% confidence interval: 0.0%-2.9%). While presence of seropositive individuals demonstrates some historical C. burnetii exposure, the placental sample confidence interval suggests 2016 shedding events were rare or absent. The location maintained the flock with little or no depopulation in 1984 and without C. burnetii vaccination during or since 1984. It is not clear how a zero-shedding rate was achieved in these sheep beyond natural immunity, and more work is required to discover and assess possible factors that may contribute towards achieving zero-shedding status. We provide the first U.S. sheep placental C. burnetii shedding update in over 60 years and demonstrate potential for C. burnetii shedding to reach undetectable levels after an outbreak event even in the absence of targeted interventions, such

  15. Genetic characterization of human hydatid cysts shows coinfection by Echinococcus canadensis G7 and Echinococcus granulosus sensu stricto G1 in Argentina.

    Science.gov (United States)

    Debiaggi, María Florencia; Soriano, Silvia Viviana; Pierangeli, Nora Beatriz; Lazzarini, Lorena Evelina; Pianciola, Luis Alfredo; Mazzeo, Melina Leonor; Moguillansky, Sergio; Farjat, Juan Angel Basualdo

    2017-09-01

    Human cystic echinococcosis caused by the larval stage of Echinococcus granulosus sensu lato (s.l.) is a highly endemic disease in the province of Neuquén, Patagonia, Argentina. Human infections with E. granulosus sensu stricto (s.s.) G1 and Echinococcus canadensis G6 were reported in Neuquén in previous studies, whereas four genotypes were identified in livestock: G1, G3, G6, and G7. The aim of this study was to identify the genotypes of E. granulosus s.l. isolates from humans of Neuquén province, Patagonia, Argentina, through the 2005-2014 period. Twenty six hydatid cysts were obtained from 21 patients. The most frequent locations were the liver and lungs. Single cysts were observed in 81.0% of patients, and combined infection of liver and lungs was detected in 9.5% of cases. Partial sequencing of mitochondrial cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 1 (nad1) genes identified the presence of E. granulosus s.s. G1 (n = 11; 42.3%) including three different partial sequences; E. canadensis G6 (n = 14; 53.8%) and E. canadensis G7 (n = 1; 3.9%). Coinfection with G1 and G7 genotypes was detected in one patient who harbored three liver cysts. Most of the liver cysts corresponded to G1 and G6 genotypes. This study presents the first report in the Americas of a human infection with E. canadensis G7 and the second worldwide report of a coinfection with two different species and genotypes of E. granulosus s.l in humans. The molecular diversity of this parasite should be considered to redesign or improve the control program strategies in endemic regions.

  16. Domestic sheep show average Coxiella burnetii seropositivity generations after a sheep-associated human Q fever outbreak and lack detectable shedding by placental, vaginal, and fecal routes.

    Directory of Open Access Journals (Sweden)

    Ryan D Oliveira

    Full Text Available Coxiella burnetii is a globally distributed zoonotic bacterial pathogen that causes abortions in ruminant livestock. In humans, an influenza-like illness results with the potential for hospitalization, chronic infection, abortion, and fatal endocarditis. Ruminant livestock, particularly small ruminants, are hypothesized to be the primary transmission source to humans. A recent Netherlands outbreak from 2007-2010 traced to dairy goats resulted in over 4,100 human cases with estimated costs of more than 300 million euros. Smaller human Q fever outbreaks of small ruminant origin have occurred in the United States, and characterizing shedding is important to understand the risk of future outbreaks. In this study, we assessed bacterial shedding and seroprevalence in 100 sheep from an Idaho location associated with a 1984 human Q fever outbreak. We observed 5% seropositivity, which was not significantly different from the national average of 2.7% for the U.S. (P>0.05. Furthermore, C. burnetii was not detected by quantitative PCR from placentas, vaginal swabs, or fecal samples. Specifically, a three-target quantitative PCR of placenta identified 0.0% shedding (exact 95% confidence interval: 0.0%-2.9%. While presence of seropositive individuals demonstrates some historical C. burnetii exposure, the placental sample confidence interval suggests 2016 shedding events were rare or absent. The location maintained the flock with little or no depopulation in 1984 and without C. burnetii vaccination during or since 1984. It is not clear how a zero-shedding rate was achieved in these sheep beyond natural immunity, and more work is required to discover and assess possible factors that may contribute towards achieving zero-shedding status. We provide the first U.S. sheep placental C. burnetii shedding update in over 60 years and demonstrate potential for C. burnetii shedding to reach undetectable levels after an outbreak event even in the absence of targeted

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

    Science.gov (United States)

    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.

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

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    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

  19. 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.

  20. 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.

  1. 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.

  2. Second generation codon optimized minicircle (CoMiC) for nonviral reprogramming of human adult fibroblasts.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  4. 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.

  5. 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.

  6. [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.

  7. 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.

  8. 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...

  9. 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.

  10. Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks.

    Science.gov (United States)

    Bour, Alexandra; Grootendorst, Jeannette; Vogel, Elise; Kelche, Christian; Dodart, Jean-Cosme; Bales, Kelly; Moreau, Pierre-Henri; Sullivan, Patrick M; Mathis, Chantal

    2008-11-21

    Apolipoprotein (apo) E4, one of three human apoE (h-apoE) isoforms, has been identified as a major genetic risk factor for Alzheimer's disease and for cognitive deficits associated with aging. However, the biological mechanisms involving apoE in learning and memory processes are unclear. A potential isoform-dependent role of apoE in cognitive processes was studied in human apoE targeted-replacement (TR) mice. These mice express either the human apoE3 or apoE4 gene under the control of endogenous murine apoE regulatory sequences, resulting in physiological expression of h-apoE in both a temporal and spatial pattern similar to humans. Male and female apoE3-TR, apoE4-TR, apoE-knockout and C57BL/6J mice (15-18 months) were tested with spatial memory and avoidance conditioning tasks. Compared to apoE3-TR mice, spatial memory in female apoE4-TR mice was impaired based on their poor performances in; (i) the probe test of the water-maze reference memory task, (ii) the water-maze working memory task and (iii) an active avoidance Y-maze task. Retention performance on a passive avoidance task was also impaired in apoE4-TR mice, but not in other genotypes. These deficits in both spatial and avoidance memory tasks may be related to the anatomical and functional abnormalities previously reported in the hippocampus and the amygdala of apoE4-TR mice. We conclude that the apoE4-TR mice provide an excellent model for understanding the mechanisms underlying apoE4-dependent susceptibility to cognitive decline.

  11. Multiple novel alternative splicing forms of FBXW7α have a translational modulatory function and show specific alteration in human cancer.

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    Yueyong Liu

    Full Text Available FBXW7 acts as a tumor suppressor through ubiquitination and degradation of multiple oncoproteins. Loss of FBXW7 expression, which could be partially attributed by the genomic deletion or mutation of FBXW7 locus, is frequently observed in various human cancers. However, the mechanisms regulating FBXW7 expression still remain poorly understood. Here we examined the 5' region of FBXW7 gene to investigate the regulation of FBXW7 expression. We identified seven alternative splicing (AS 5'-UTR forms of FBXW7α that are composed of multiple novel non-coding exons. A significant difference in translational efficiency among these 5'-UTRs variants was observed by in vivo Luciferase reporter assay and Western blot. Furthermore, we found that the mRNA level of the AS form with high translational efficiency was specifically reduced in more than 80% of breast cancer cell lines and in more than 50% of human primary cancers from various tissues. In addition, we also identified mutations of FBXW7 in prostate cancers (5.6%, kidney cancers (16.7%, and bladder cancers (18.8%. Our results suggest that in addition to mutation, differential expression of FBXW7α AS forms with different translational properties may serve as a novel mechanism for inactivation of FBXW7 in human cancer.

  12. 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.

  13. 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.

  14. [Development of a web-based education program for nurses working in nursing homes on human rights of older adults].

    Science.gov (United States)

    Kim, Ki-Kyong

    2010-08-01

    This study was done to develop a web-based education program for nurses working in nursing homes. The focus was on the rights of older adults. The program was designed based on the Network-Based Instructional System Design (NBISD) model and was operated and evaluated between July 2007 and June 2008. Out of nursing records of 40 residents from a nursing home, the final 7 cases were deducted through classification using the Resource Utilization Group (RUG)-III. The data on needs for education was collected from 28 nurses working in 15 nursing homes located in Seoul and Gyeonggi Province, who agreed to complete a self-report questionnaire. A comprehensive review of the literature and two focus groups interviews were used to search for risk factors and guidelines for protection of human rights. The education program was developed based on Kolb's experiential learning model and composed of 5 units, which included content on types of human rights and rights to death with dignity, elder abuse, physical liberty, and self-determination. The program was positively evaluated showing a score of 3.35 (SD=0.37) out of 4. The educational program developed in this study should promote nurses' sensitivity to the rights of elders and improve nurses' behaviors in protecting the rights of elders residing in nursing homes.

  15. Rotating three-dimensional dynamic culture of adult human bone marrow-derived cells for tissue engineering of hyaline cartilage.

    Science.gov (United States)

    Sakai, Shinsuke; Mishima, Hajime; Ishii, Tomoo; Akaogi, Hiroshi; Yoshioka, Tomokazu; Ohyabu, Yoshimi; Chang, Fei; Ochiai, Naoyuki; Uemura, Toshimasa

    2009-04-01

    The method of constructing cartilage tissue from bone marrow-derived cells in vitro is considered a valuable technique for hyaline cartilage regenerative medicine. Using a rotating wall vessel (RWV) bioreactor developed in a NASA space experiment, we attempted to efficiently construct hyaline cartilage tissue from human bone marrow-derived cells without using a scaffold. Bone marrow aspirates were obtained from the iliac crest of nine patients during orthopedic operation. After their proliferation in monolayer culture, the adherent cells were cultured in the RWV bioreactor with chondrogenic medium for 2 weeks. Cells from the same source were cultured in pellet culture as controls. Histological and immunohistological evaluations (collagen type I and II) and quantification of glycosaminoglycan were performed on formed tissues and compared. The engineered constructs obtained using the RWV bioreactor showed strong features of hyaline cartilage in terms of their morphology as determined by histological and immunohistological evaluations. The glycosaminoglycan contents per microg DNA of the tissues were 10.01 +/- 3.49 microg/microg DNA in the case of the RWV bioreactor and 6.27 +/- 3.41 microg/microg DNA in the case of the pellet culture, and their difference was significant. The RWV bioreactor could provide an excellent environment for three-dimensional cartilage tissue architecture that can promote the chondrogenic differentiation of adult human bone marrow-derived cells.

  16. Transcriptomic Analysis of Lung Tissue from Cigarette Smoke-Induced Emphysema Murine Models and Human Chronic Obstructive Pulmonary Disease Show Shared and Distinct Pathways.

    Science.gov (United States)

    Yun, Jeong H; Morrow, Jarrett; Owen, Caroline A; Qiu, Weiliang; Glass, Kimberly; Lao, Taotao; Jiang, Zhiqiang; Perrella, Mark A; Silverman, Edwin K; Zhou, Xiaobo; Hersh, Craig P

    2017-07-01

    Although cigarette smoke (CS) is the primary risk factor for chronic obstructive pulmonary disease (COPD), the underlying molecular mechanisms for the significant variability in developing COPD in response to CS are incompletely understood. We performed lung gene expression profiling of two different wild-type murine strains (C57BL/6 and NZW/LacJ) and two genetic models with mutations in COPD genome-wide association study genes (HHIP and FAM13A) after 6 months of chronic CS exposure and compared the results to human COPD lung tissues. We identified gene expression patterns that correlate with severity of emphysema in murine and human lungs. Xenobiotic metabolism and nuclear erythroid 2-related factor 2-mediated oxidative stress response were commonly regulated molecular response patterns in C57BL/6, Hhip +/- , and Fam13a -/- murine strains exposed chronically to CS. The CS-resistant Fam13a -/- mouse and NZW/LacJ strain revealed gene expression response pattern differences. The Fam13a -/- strain diverged in gene expression compared with C57BL/6 control only after CS exposure. However, the NZW/LacJ strain had a unique baseline expression pattern, enriched for nuclear erythroid 2-related factor 2-mediated oxidative stress response and xenobiotic metabolism, and converged to a gene expression pattern similar to the more susceptible wild-type C57BL/6 after CS exposure. These results suggest that distinct molecular pathways may account for resistance to emphysema. Surprisingly, there were few genes commonly modulated in mice and humans. Our study suggests that gene expression responses to CS may be largely species and model dependent, yet shared pathways could provide biologically significant insights underlying individual susceptibility to CS.

  17. 3ircular dichroism simulation shows a site-II-to-site-I displacement of human serum albumin-bound diclofenac by ibuprofen

    OpenAIRE

    Yamasaki, Keishi; Rahman, Mohammed Hablbur; Tsutsumi, Yasuhiro; Maruyama, Toru; Ahmed, Shamim; Kragh-Hansen; Otagiri, Masaki

    2000-01-01

    Purpose: The purpose of this study was to confirm the hypothesis that a site-II-to-site-I displacement takes place when some nonsteroidal anti-inflammatory drugs are displaced by another drug from their high-affinity binding site to a site of lower affinity on human serum albumin (HSA).Methods: Diclofenac, sodium salt, was used as a representative example because of its prominent reversal of the Cotton effect. Effects of site-specific drugs on the free fraction of diclofenac were determined b...

  18. 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.

  19. The predictive nature of transcript expression levels on protein expression in adult human brain.

    Science.gov (United States)

    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.

  20. Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb 14C

    Science.gov (United States)

    Heinemeier, Katja Maria; Schjerling, Peter; Heinemeier, Jan; Magnusson, Stig Peter; Kjaer, Michael

    2013-01-01

    Tendons are often injured and heal poorly. Whether this is caused by a slow tissue turnover is unknown, since existing data provide diverging estimates of tendon protein half-life that range from 2 mo to 200 yr. With the purpose of determining life-long turnover of human tendon tissue, we used the 14C bomb-pulse method. This method takes advantage of the dramatic increase in atmospheric levels of 14C, produced by nuclear bomb tests in 1955–1963, which is reflected in all living organisms. Levels of 14C were measured in 28 forensic samples of Achilles tendon core and 4 skeletal muscle samples (donor birth years 1945–1983) with accelerator mass spectrometry (AMS) and compared to known atmospheric levels to estimate tissue turnover. We found that Achilles tendon tissue retained levels of 14C corresponding to atmospheric levels several decades before tissue sampling, demonstrating a very limited tissue turnover. The tendon concentrations of 14C approximately reflected the atmospheric levels present during the first 17 yr of life, indicating that the tendon core is formed during height growth and is essentially not renewed thereafter. In contrast, 14C levels in muscle indicated continuous turnover. Our observation provides a fundamental premise for understanding tendon function and pathology, and likely explains the poor regenerative capacity of tendon tissue.—Heinemeier, K. M., Schjerling, P., Heinemeier, J., Magnusson, S. P., Kjaer, M. Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb 14C. PMID:23401563

  1. 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.

  2. Genome-Wide Screening of Genes Showing Altered Expression in Liver Metastases of Human Colorectal Cancers by cDNA Microarray

    Directory of Open Access Journals (Sweden)

    Rempei Yanagawa

    2001-01-01

    Full Text Available In spite of intensive and increasingly successful attempts to determine the multiple steps involved in colorectal carcinogenesis, the mechanisms responsible for metastasis of colorectal tumors to the liver remain to be clarified. To identify genes that are candidates for involvement in the metastatic process, we analyzed genome-wide expression profiles of 10 primary colorectal cancers and their corresponding metastatic lesions by means of a cDNA microarray consisting of 9121 human genes. This analysis identified 40 genes whose expression was commonly upregulated in metastatic lesions, and 7 that were commonly downregulated. The upregulated genes encoded proteins involved in cell adhesion, or remodeling of the actin cytoskeleton. Investigation of the functions of more of the altered genes should improve our understanding of metastasis and may identify diagnostic markers and/or novel molecular targets for prevention or therapy of metastatic lesions.

  3. The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus.

    Science.gov (United States)

    Flisiak, Robert; Horban, Andrzej; Gallay, Philippe; Bobardt, Michael; Selvarajah, Suganya; Wiercinska-Drapalo, Alicja; Siwak, Ewa; Cielniak, Iwona; Higersberger, Jozef; Kierkus, Jarek; Aeschlimann, Christian; Grosgurin, Pierre; Nicolas-Métral, Valérie; Dumont, Jean-Maurice; Porchet, Hervé; Crabbé, Raf; Scalfaro, Pietro

    2008-03-01

    Debio-025 is an oral cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus activity in vitro. Its effect on viral load as well as its influence on intracellular Cyp levels was investigated in a randomized, double-blind, placebo-controlled study. Mean hepatitis C viral load decreased significantly by 3.6 log(10) after a 14-day oral treatment with 1200 mg twice daily (P CypB) levels in peripheral blood mononuclear cells decreased from 67 +/- 6 (standard error) ng/mg protein (baseline) to 5 +/- 1 ng/mg protein at day 15 (P CypB levels, coinciding with the decrease in hepatitis C viral load. These are the first preliminary human data supporting the hypothesis that CypB may play an important role in hepatitis C virus replication and that Cyp inhibition is a valid target for the development of anti-hepatitis C drugs.

  4. 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...

  5. The human CD38 monoclonal antibody daratumumab shows anti-tumor activity and hampers leukemia-microenvironment interactions in chronic lymphocytic leukemia

    Science.gov (United States)

    Matas-Céspedes, Alba; Vidal-Crespo, Anna; Rodriguez, Vanina; Villamor, Neus; Delgado, Julio; Giné, Eva; Roca-Ho, Heleia; Menéndez, Pablo; Campo, Elías; López-Guillermo, Armando; Colomer, Dolors; Roué, Gaël; Wiestner, Adrian; Parren, Paul W.H.I.; Doshi, Parul; van Bueren, Jeroen Lammerts; Pérez-Galán, Patricia

    2016-01-01

    Purpose To establish a proof-of-concept for the efficacy of the anti-CD38 antibody daratumumab in the poor prognosis CD38+ CLL subtype. Experimental design The mechanism of action of daratumumab was assessed in CLL primary cells and cell lines using peripheral blood mononuclear cells to analyze antibody-dependent cell cytotoxicity (ADCC), murine and human macrophages to study antibody-dependent cell phagocytosis (ADCP) or human serum to analyze complement-dependent cytotoxicity (CDC). The effect of daratumumab on CLL cell migration and adhesion to extracellular matrix was characterized. Daratumumab activity was validated in two in vivo models. Results Daratumumab demonstrated efficient lysis of patient-derived CLL cells and cell lines by ADCC in vitro and ADCP both in vitro and in vivo, while exhibited negligible CDC in these cells. To demonstrate the therapeutic effect of daratumumab in CLL, we generated a disseminated CLL mouse model with the CD38+ MEC2 cell line and CLL patient derived xenografts (CLL-PDX). Daratumumab significantly prolonged overall survival of MEC2 mice, completely eliminated cells from the infiltrated organs and significantly reduced disease burden in the spleen of CLL-PDX. The effect of daratumumab on patient-derived CLL cell dissemination was demonstrated in vitro by its effect on CXCL12-induced migration and in vivo by interfering with CLL cell homing to spleen in NSG mice. Daratumumab also reduced adhesion of CLL cells to VCAM-1, accompanied by down-regulation of the matrix metalloproteinase MMP9. Conclusions These unique and substantial effects of daratumumab on CLL viability and dissemination support the investigation of its use in a clinical setting of CLL. PMID:27637890

  6. Clusters of ancestrally related genes that show paralogy in whole or in part are a major feature of the genomes of humans and other species.

    Directory of Open Access Journals (Sweden)

    Michael B Walker

    Full Text Available Arrangements of genes along chromosomes are a product of evolutionary processes, and we can expect that preferable arrangements will prevail over the span of evolutionary time, often being reflected in the non-random clustering of structurally and/or functionally related genes. Such non-random arrangements can arise by two distinct evolutionary processes: duplications of DNA sequences that give rise to clusters of genes sharing both sequence similarity and common sequence features and the migration together of genes related by function, but not by common descent. To provide a background for distinguishing between the two, which is important for future efforts to unravel the evolutionary processes involved, we here provide a description of the extent to which ancestrally related genes are found in proximity.Towards this purpose, we combined information from five genomic datasets, InterPro, SCOP, PANTHER, Ensembl protein families, and Ensembl gene paralogs. The results are provided in publicly available datasets (http://cgd.jax.org/datasets/clustering/paraclustering.shtml describing the extent to which ancestrally related genes are in proximity beyond what is expected by chance (i.e. form paraclusters in the human and nine other vertebrate genomes, as well as the D. melanogaster, C. elegans, A. thaliana, and S. cerevisiae genomes. With the exception of Saccharomyces, paraclusters are a common feature of the genomes we examined. In the human genome they are estimated to include at least 22% of all protein coding genes. Paraclusters are far more prevalent among some gene families than others, are highly species or clade specific and can evolve rapidly, sometimes in response to environmental cues. Altogether, they account for a large portion of the functional clustering previously reported in several genomes.

  7. 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

  8. Higher prevalence of human papillomavirus infection in adolescent and young adult girls belonging to different Indian tribes with varied socio-sexual lifestyle.

    Directory of Open Access Journals (Sweden)

    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.

  9. A new frailty syndrome: central obesity and frailty in older adults with the human immunodeficiency virus.

    Science.gov (United States)

    Shah, Krupa; Hilton, Tiffany N; Myers, Lauren; Pinto, Jonathan F; Luque, Amneris E; Hall, William J

    2012-03-01

    To evaluate the relationships between body composition and physical frailty in community-dwelling older adults with the human immunodeficiency virus (HIV) (HOA). Cross-sectional. Academic hospital-based infectious disease clinic in Rochester, New York. Forty community-dwelling HOA aged 50 and older undergoing antiretroviral therapy who were able to ambulate without assistive devices with a mean age of 58, a mean BMI of 29.0 kg/m(2), mean CD4 count of 569 cells/mL, and a mean duration since HIV diagnosis of 17 years; 28% were female and 57% Caucasian. Subjective and objective measures of functional status were evaluated using the Physical Performance Test (PPT), the graded treadmill test, knee strength, gait speed, balance, and the Functional Status Questionnaire (FSQ). Body composition was evaluated using dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI). Sixty percent (25/40) of the participants met standard criteria for physical frailty. Frail (FR) and nonfrail (NF) participants were comparable in age, sex, CD4 count, and viral load. FR HOA had greater impairments in PPT, peak oxygen uptake, FSQ, walking speed, balance, and muscle quality than NF HOA. FR HOA had a greater body mass index (BMI), fat mass, and truncal fat with lipodystrophy. Moreover, PPT score was inversely related to trunk fat (correlation coefficient (r) = -0.34; P = .04) and ratio of intermuscular fat to total fat (r = -0.60; P = .02) after adjusting for covariates. HOA represent an emerging cohort of older adults who frequently experience frailty at a much younger age than the general older population. Central obesity and fat redistribution are important predictors of frailty in community-dwelling HOA. These findings suggest that physical frailty in HOA may be amenable to lifestyle interventions, especially exercise and diet therapy. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

  10. 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.

  11. 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.

  12. Knock-in strategy at 3'-end of Crx gene by CRISPR/Cas9 system shows the gene expression profiles during human photoreceptor differentiation.

    Science.gov (United States)

    Homma, Kohei; Usui, Sumiko; Kaneda, Makoto

    2017-03-01

    Fluorescent reporter gene knock-in induced pluripotent stem cell (iPSC) lines have been used to evaluate the efficiency of differentiation into specific cell lineages. Here, we report a knock-in strategy for the generation of human iPSC reporter lines in which a 2A peptide sequence and a red fluorescent protein (E2-Crimson) gene were inserted at the termination codon of the cone-rod homeobox (Crx) gene, a photoreceptor-specific transcriptional factor gene. The knock-in iPSC lines were differentiated into fluorescence-expressing cells in 3D retinal differentiation culture, and the fluorescent cells also expressed Crx specifically in the nucleus. We found that the fluorescence intensity was positively correlated with the expression levels of Crx mRNA and that fluorescent cells expressed rod photoreceptor-specific genes in the later stage of differentiation. Finally, we treated the fluorescent cells with DAPT, a Notch inhibitor, and found that DAPT-enhanced retinal differentiation was associated with up-regulation of Crx, Otx2 and NeuroD1, and down-regulation of Hes5 and Ngn2. These suggest that this knock-in strategy at the 3'-end of the target gene, combined with the 2A peptide linked to fluorescent proteins, offers a useful tool for labeling specific cell lineages or monitoring expression of any marker genes without affecting the function of the target gene. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  13. Human neuroblastoma SH-SY5Y cells show increased resistance to hyperthermic stress after differentiation, associated with elevated levels of Hsp72.

    Science.gov (United States)

    Cheng, Lesley; Smith, Danielle J; Anderson, Robin L; Nagley, Phillip

    2011-01-01

    Terminally differentiated neurones in the central nervous system need to be protected from stress. We ask here whether differentiation of progenitor cells to neurones is accompanied by up-regulation of Hsp72, with acquisition of enhanced thermotolerance. Human neuroblastoma SH-SY5Y cells were propagated in an undifferentiated form and subsequently differentiated into neurone-like cells. Thermotolerance tests were carried out by exposure of cells to various temperatures, monitoring nuclear morphology as index of cell death. Abundance of Hsp72 was measured in cell lysates by western immunoblotting. The differentiation of SH-SY5Y cells was accompanied by increased expression of Hsp72. Further, in both cell states, exposure to mild hyperthermic stress (43°C for 30 min) increased Hsp72 expression. After differentiation, SH-SY5Y cells were more resistant to hyperthermic stress compared to their undifferentiated state, correlating with levels of Hsp72. Stable exogenous expression of Hsp72 in SH-SY5Y cells (transfected line 5YHSP72.1, containing mildly elevated levels of Hsp72), led to enhanced resistance to hyperthermic stress. Hsp72 was found to be inducible in undifferentiated 5YHSP72.1 cells; such heat-treated cells displayed enhanced thermotolerance. Treatment of cells with KNK437, a suppressor of Hsp72 induction, resulted in acute thermosensitisation of all cell types tested here. Hsp72 has a major role in the enhanced hyperthermic resistance acquired during neuronal differentiation of SH-SY5Y cells. These findings model the requirement in intact organisms for highly differentiated neurones to be specially protected against thermal stress.

  14. The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, But Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults

    Science.gov (United States)

    Dinges, Warren; Girard, Pierre-Marie; Podzamczer, Daniel; Brockmeyer, Norbert H.; García, Felipe.; Harrer, Thomas; Lelievre, Jean-Daniel; Frank, Ian; Colin De Verdière, Nathalie; Yeni, Guy-Patrick; Ortega Gonzalez, Enrique; Rubio, Rafael; Clotet Sala, Bonaventura; DeJesus, Edwin; Pérez-Elias, Maria Jesus; Launay, Odile; Pialoux, Gilles; Slim, Jihad; Weiss, Laurence; Bouchaud, Olivier; Felizarta, Franco; Meurer, Anja; Raffi, François; Esser, Stefan; Katlama, Christine; Koletar, Susan L.; Mounzer, Karam; Swindells, Susan; Baxter, John D.; Schneider, Stefan; Chas, Julie; Molina, Jean-Michel; Koutsoukos, Marguerite; Collard, Alix; Bourguignon, Patricia; Roman, François

    2016-01-01

    Abstract The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults. This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B_2 group, N = 64) or 3 (F4/AS01B_3 group, N = 62) doses of F4/AS01B or placebo (control group, N = 64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD4+ T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks. At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B_2 and control group (0.073 log10 copies/mL [97.5% confidence interval (CI): −0.088; 0.235]), or F4/AS01B_3 and control group (−0.096 log10 copies/mL [97.5% CI: −0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD4+ T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/AS01B_2 group: angioedema). F4/AS01B induced polyfunctional F4-specific CD4+ T-cells, but had no significant impact on F4-specific CD8+ T-cell and anti-F4 antibody levels. F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD4+ T-cell responses, but did not reduce HIV-1 VL, impact CD4+ T-cells count, delay ART initiation, or prevent HIV-1 related clinical events. PMID:26871794

  15. The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, But Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults: A Randomized Controlled Trial.

    Science.gov (United States)

    Dinges, Warren; Girard, Pierre-Marie; Podzamczer, Daniel; Brockmeyer, Norbert H; García, Felipe; Harrer, Thomas; Lelievre, Jean-Daniel; Frank, Ian; Colin De Verdière, Nathalie; Yeni, Guy-Patrick; Ortega Gonzalez, Enrique; Rubio, Rafael; Clotet Sala, Bonaventura; DeJesus, Edwin; Pérez-Elias, Maria Jesus; Launay, Odile; Pialoux, Gilles; Slim, Jihad; Weiss, Laurence; Bouchaud, Olivier; Felizarta, Franco; Meurer, Anja; Raffi, François; Esser, Stefan; Katlama, Christine; Koletar, Susan L; Mounzer, Karam; Swindells, Susan; Baxter, John D; Schneider, Stefan; Chas, Julie; Molina, Jean-Michel; Koutsoukos, Marguerite; Collard, Alix; Bourguignon, Patricia; Roman, François

    2016-02-01

    The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults.This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B_2 group, N = 64) or 3 (F4/AS01B_3 group, N = 62) doses of F4/AS01B or placebo (control group, N = 64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD4 T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks.At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B_2 and control group (0.073 log10 copies/mL [97.5% confidence interval (CI): -0.088; 0.235]), or F4/AS01B_3 and control group (-0.096 log10 copies/mL [97.5% CI: -0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD4 T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/AS01B_2 group: angioedema). F4/AS01B induced polyfunctional F4-specific CD4 T-cells, but had no significant impact on F4-specific CD8 T-cell and anti-F4 antibody levels.F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD4 T-cell responses, but did not reduce HIV-1 VL, impact CD4 T-cells count, delay ART initiation, or prevent HIV-1 related clinical events.

  16. 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)

  17. DNA Methylation Profiling of Human Prefrontal Cortex Neurons in Heroin Users Shows Significant Difference between Genomic Contexts of Hyper- and Hypomethylation and a Younger Epigenetic Age

    Directory of Open Access Journals (Sweden)

    Alexey Kozlenkov

    2017-05-01

    Full Text Available We employed Illumina 450 K Infinium microarrays to profile DNA methylation (DNAm in neuronal nuclei separated by fluorescence-activated sorting from the postmortem orbitofrontal cortex (OFC of heroin users who died from heroin overdose (N = 37, suicide completers (N = 22 with no evidence of heroin use and from control subjects who did not abuse illicit drugs and died of non-suicide causes (N = 28. We identified 1298 differentially methylated CpG sites (DMSs between heroin users and controls, and 454 DMSs between suicide completers and controls (p < 0.001. DMSs and corresponding genes (DMGs in heroin users showed significant differences in the preferential context of hyper and hypo DM. HyperDMSs were enriched in gene bodies and exons but depleted in promoters, whereas hypoDMSs were enriched in promoters and enhancers. In addition, hyperDMGs showed preference for genes expressed specifically by glutamatergic as opposed to GABAergic neurons and enrichment for axonogenesis- and synaptic-related gene ontology categories, whereas hypoDMGs were enriched for transcription factor activity- and gene expression regulation-related terms. Finally, we found that the DNAm-based “epigenetic age” of neurons from heroin users was younger than that in controls. Suicide-related results were more difficult to interpret. Collectively, these findings suggest that the observed DNAm differences could represent functionally significant marks of heroin-associated plasticity in the OFC.

  18. Persisting fetal clonotypes influence the structure and overlap of adult human T cell receptor repertoires.

    Directory of Open Access Journals (Sweden)

    Mikhail V Pogorelyy

    2017-07-01

    Full Text Available The diversity of T-cell receptors recognizing foreign pathogens is generated through a highly stochastic recombination process, making the independent production of the same sequence rare. Yet unrelated individuals do share receptors, which together constitute a "public" repertoire of abundant clonotypes. The TCR repertoire is initially formed prenatally, when the enzyme inserting random nucleotides is downregulated, producing a limited diversity subset. By statistically analyzing deep sequencing T-cell repertoire data from twins, unrelated individuals of various ages, and cord blood, we show that T-cell clones generated before birth persist and maintain high abundances in adult organisms for decades, slowly decaying with age. Our results suggest that large, low-diversity public clones are created during pre-natal life, and survive over long periods, providing the basis of the public repertoire.

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

    Science.gov (United States)

    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

  20. Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states

    International Nuclear Information System (INIS)

    Sarver, Aaron L; Cunningham, Julie M; Subramanian, Subbaya; Wang, Liang; Smyrk, Tom C; Rodrigues, Cecilia MP; Thibodeau, Stephen N; Steer, Clifford J; French, Amy J; Borralho, Pedro M; Thayanithy, Venugopal; Oberg, Ann L; Silverstein, Kevin AT; Morlan, Bruce W; Riska, Shaun M; Boardman, Lisa A

    2009-01-01

    Colon cancer arises from the accumulation of multiple genetic and epigenetic alterations to normal colonic tissue. microRNAs (miRNAs) are small, non-coding regulatory RNAs that post-transcriptionally regulate gene expression. Differential miRNA expression in cancer versus normal tissue is a common event and may be pivotal for tumor onset and progression. To identify miRNAs that are differentially expressed in tumors and tumor subtypes, we carried out highly sensitive expression profiling of 735 miRNAs on samples obtained from a statistically powerful set of tumors (n = 80) and normal colon tissue (n = 28) and validated a subset of this data by qRT-PCR. Tumor specimens showed highly significant and large fold change differential expression of the levels of 39 miRNAs including miR-135b, miR-96, miR-182, miR-183, miR-1, and miR-133a, relative to normal colon tissue. Significant differences were also seen in 6 miRNAs including miR-31 and miR-592, in the direct comparison of tumors that were deficient or proficient for mismatch repair. Examination of the genomic regions containing differentially expressed miRNAs revealed that they were also differentially methylated in colon cancer at a far greater rate than would be expected by chance. A network of interactions between these miRNAs and genes associated with colon cancer provided evidence for the role of these miRNAs as oncogenes by attenuation of tumor suppressor genes. Colon tumors show differential expression of miRNAs depending on mismatch repair status. miRNA expression in colon tumors has an epigenetic component and altered expression that may reflect a reversion to regulatory programs characteristic of undifferentiated proliferative developmental states

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

    Science.gov (United States)

    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.

  2. Different DNA damage response of cis and trans isomers of commonly used UV filter after the exposure on adult human liver stem cells and human lymphoblastoid cells.

    Science.gov (United States)

    Sharma, Anežka; Bányiová, Katarína; Babica, Pavel; El Yamani, Naouale; Collins, Andrew Richard; Čupr, Pavel

    2017-09-01

    2-ethylhexyl 4-methoxycinnamate (EHMC), used in many categories of personal care products (PCPs), is one of the most discussed ultraviolet filters because of its endocrine-disrupting effects. EHMC is unstable in sunlight and can be transformed from trans-EHMC to emergent cis-EHMC. Toxicological studies are focusing only on trans-EHMC; thus the toxicological data for cis-EHMC are missing. In this study, the in vitro genotoxic effects of trans- and cis-EHMC on adult human liver stem cells HL1-hT1 and human-derived lymphoblastoid cells TK-6 using a high-throughput comet assay were studied. TK-6 cells treated with cis-EHMC showed a high level of DNA damage when compared to untreated cells in concentrations 1.56 to 25μgmL -1 . trans-EHMC showed genotoxicity after exposure to the two highest concentrations 12.5 and 25μgmL -1 . The increase in DNA damage on HL1-hT1 cells induced by cis-EHMC and trans-EHMC was detected at the concentration 25μgmL -1 . The No observed adverse effect level (NOAEL, mg kg -1 bwday -1 ) was determined using a Quantitative in vitro to in vivo extrapolation (QIVIVE) approach: NOAEL trans-EHMC =3.07, NOAEL cis-EHMC =0.30 for TK-6 and NOAEL trans-EHMC =26.46, NOAEL cis-EHMC =20.36 for HL1-hT1. The hazard index (HI) was evaluated by comparing the reference dose (RfD, mgkg -1 bwday -1 ) obtained from our experimental data with the chronic daily intake (CDI) of the female population. Using comet assay experimental data with the more sensitive TK-6 cells, HI cis-EHMC was 7 times higher than HI trans-EHMC . In terms of CDI, relative contributions were; dermal exposure route>oral>inhalation. According to our results we recommend the RfD trans-EHMC =0.20 and RfD cis-EHMC =0.02 for trans-EHMC and cis-EHMC, respectively, to use for human health risk assessment. The significant difference in trans-EHMC and cis-EHMC response points to the need for toxicological reevaluation and application reassessment of both isomers in PCPs. Copyright © 2017 Elsevier B

  3. An association between human hippocampal volume and topographical memory in healthy young adults.

    Directory of Open Access Journals (Sweden)

    Tom eHartley

    2012-12-01

    Full Text Available The association between human hippocampal structure and topographical memory was investigated in healthy adults (N=30. Structural MR images were acquired, and voxel-based morphometry (VBM was used to estimate local gray matter volume throughout the brain. A complementary automated mesh-based segmentation approach was used to independently isolate and measure specified structures including the hippocampus. Topographical memory was assessed using a version of the Four Mountains Task, a short test designed to target hippocampal spatial function. Each item requires subjects to briefly study a landscape scene before recognizing the depicted place from a novel viewpoint and under altered non-spatial conditions when presented amongst similar alternative scenes. Positive correlations between topographical memory performance and hippocampal volume were observed in both VBM and segmentation-based analyses. Score on the topographical memory task was also correlated with the volume of some subcortical structures, extra-hippocampal gray matter and total brain volume, with the most robust and extensive covariation seen in circumscribed neocortical regions in the insula and anterior temporal lobes. Taken together with earlier findings, the results suggest that global variations in brain morphology affect the volume of the hippocampus and its specific contribution to topographical memory. We speculate that behavioral variation might arise directly through the impact of resource constraints on spatial representations in the hippocampal formation and its inputs, and perhaps indirectly through an increased reliance on non-allocentric strategies.

  4. Growth of the human lens in the Indian adult population: Preliminary observations

    Directory of Open Access Journals (Sweden)

    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.

  5. Redetection of human papillomavirus type 16 infections of the cervix in mid-adult life

    Directory of Open Access Journals (Sweden)

    Aaron Ermel

    2018-06-01

    Full Text Available Purpose: To assess whether HPV 16 originally detected in adolescent women can be redetected in adulthood. Methods: A convenience sample of 27 adult women with known HPV 16 detection during adolescence was assessed for HPV 16 redetection. A comparison of the long control region (LCR DNA sequences was performed on some of the original and redetected HPV 16 isolates. Results: Median age at reenrollment was 27.5 years (interquartile range of 26.7–29.6. Reenrollment occurred six years on average after the original HPV 16 detection. Eleven of 27 women had HPV 16 redetected. Some of these HPV 16 infections had apparently cleared during adolescence. LCR sequencing was successful in paired isolates from 6 women; in 5 of 6 cases the redetected HPV 16 isolates were identical to those detected during adolescence, Conclusions: HPV 16 may be episodically detected in young women, even over long time periods. HPV 16 redetection with identical LCR sequences suggests low-level persistent infection rather than true clearance, although newly acquired infection with an identical HPV 16 isolate cannot be excluded. However, this study suggests that a new HPV 16-positive test in a clinical setting may not indicate a new infection. Keywords: Human papillomavirus (HPV, Redetection, Latency, Long control region, Sequencing

  6. A novel mouse model carrying a human cytoplasmic dynein mutation shows motor behavior deficits consistent with Charcot-Marie-Tooth type 2O disease.

    Science.gov (United States)

    Sabblah, Thywill T; Nandini, Swaran; Ledray, Aaron P; Pasos, Julio; Calderon, Jami L Conley; Love, Rachal; King, Linda E; King, Stephen J

    2018-01-29

    Charcot-Marie-Tooth disease (CMT) is a peripheral neuromuscular disorder in which axonal degeneration causes progressive loss of motor and sensory nerve function. The loss of motor nerve function leads to distal muscle weakness and atrophy, resulting in gait problems and difficulties with walking, running, and balance. A mutation in the cytoplasmic dynein heavy chain (DHC) gene was discovered to cause an autosomal dominant form of the disease designated Charcot-Marie-Tooth type 2 O disease (CMT2O) in 2011. The mutation is a single amino acid change of histidine into arginine at amino acid 306 (H306R) in DHC. In order to understand the onset and progression of CMT2, we generated a knock-in mouse carrying the corresponding CMT2O mutation (H304R/+). We examined H304R/+ mouse cohorts in a 12-month longitudinal study of grip strength, tail suspension, and rotarod assays. H304R/+ mice displayed distal muscle weakness and loss of motor coordination phenotypes consistent with those of individuals with CMT2. Analysis of the gastrocnemius of H304R/+ male mice showed prominent defects in neuromuscular junction (NMJ) morphology including reduced size, branching, and complexity. Based on these results, the H304R/+ mouse will be an important model for uncovering functions of dynein in complex organisms, especially related to CMT onset and progression.

  7. A yeast glycolipid biosurfactant, mannosylerythritol lipid, shows potential moisturizing activity toward cultured human skin cells: the recovery effect of MEL-A on the SDS-damaged human skin cells.

    Science.gov (United States)

    Morita, Tomotake; Kitagawa, Masaru; Suzuki, Michiko; Yamamoto, Shuhei; Sogabe, Atsushi; Yanagidani, Shusaku; Imura, Tomohiro; Fukuoka, Tokuma; Kitamoto, Dai

    2009-01-01

    Mannosylerythritol lipids (MELs) are produced in large amounts from renewable vegetable oils by Pseudozyma antarctica, and are the most promising biosurfactants known due to its versatile interfacial and biochemical actions. In order to broaden the application in cosmetics and pharmaceuticals, the skin care property of MEL-A, the major component of MELs, was investigated using a three-dimensional cultured human skin model. The skin cells were cultured and treated with sodium dodecyl sulfate (SDS) solution of 1 wt%, and the effects of different lipids on the SDS-damaged cells were then evaluated on the basis of the cell viability. The viability of the damaged cells was markedly recovered by the addition of MEL-A in a dose-dependent manner. Compared to the control, MEL-A solutions of 5 wt% and 10 wt% gave the recovery rate of 73% and 91%, respectively, while ceramide solution of 1 wt% gave the rate of over 100%. This revealed that MEL-A shows a ceramide-like moisturizing activity toward the skin cells. Considering the drawbacks of natural ceramides, namely limited amount and high production cost, the yeast biosurfactants should have a great potential as a novel moisturizer for treating the damaged skin.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. 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.

  10. A comparative study of the structural organization of spheres derived from the adult human subventricular zone and glioblastoma biopsies

    International Nuclear Information System (INIS)

    Vik-Mo, Einar Osland; Sandberg, Cecilie; Joel, Mrinal; Stangeland, Biljana; Watanabe, Yasuhiro; Mackay-Sim, Alan; Moe, Morten Carstens; Murrell, Wayne; Langmoen, Iver Arne

    2011-01-01

    Sphere forming assays have been useful to enrich for stem like cells in a range of tumors. The robustness of this system contrasts the difficulties in defining a stem cell population based on cell surface markers. We have undertaken a study to describe the cellular and organizational composition of tumorspheres, directly comparing these to neurospheres derived from the adult human subventricular zone (SVZ). Primary cell cultures from brain tumors were found to contain variable fractions of cells positive for tumor stem cell markers (CD133 (2-93%)/SSEA1 (3-15%)/CXCR4 (1-72%)). All cultures produced tumors upon xenografting. Tumorspheres contained a heterogeneous population of cells, but were structurally organized with stem cell markers present at the core of spheres, with markers of more mature glial progenitors and astrocytes at more peripheral location. Ultrastructural studies showed that tumorspheres contained a higher fraction of electron dense cells in the core than the periphery (36% and 19%, respectively). Neurospheres also contained a heterogeneous cell population, but did not have an organization similar to tumorspheres. Although tumorspheres clearly display irregular and neoplastic cells, they establish an organized structure with an outward gradient of differentiation. We suggest that this organization is central in maintaining the tumor stem cell pool.

  11. Storing live embryonic and adult human cartilage grafts for transplantation using a joint simulating device.

    Science.gov (United States)

    Cohen, I; Robinson, D; Cohen, N; Nevo, Z

    2000-11-01

    Cartilage transplantation as a means to replace damaged articular surfaces is of interest. A major obstacle is the long-term preservation of cartilage grafts. The commonly used technique of freezing the grafts inevitably leads to cellular death. The current study compares the technique to an innovative approach using a pulsed-pressure perfusion system termed a joint simulating device (JSD), intended to simulate intra-articular mechanical forces. Human articular cartilage explants were harvested from both embryonic epiphyseal tissue and femoral heads of elderly women (over 70 years of age) undergoing a partial joint replacement (hemi-arthroplasty) and were divided in two groups: half of the samples were incubated in the JSD while the remaining half were grown in static culture within tissue culture plates. After 10 days all samples were evaluated for: (a) cell vitality as assessed by image analysis and XTT assay; (b) biosynthetic activity as expressed by radioactive sulfate incorporation into glycosaminoglycans (GAG's); and (c) proteoglycan content as assessed by alcian blue staining intensity. A 10-fold increase in sulfate incorporation in samples held in the JSD compared to the static culture group was observed in embryonic cartilage. In adult cartilage culture in the JSD elevated sulfate incorporation by threefold as compared to static culture. Central necrosis was observed in specimens grown in the static culture plates, while it did not occur in the samples held in the JSD. Cell vitality as assessed by XTT assay was significantly better in the JSD group as compared to static culture. The difference was more pronounced in the embryonic specimens as compared to adult cartilage. The specimens cultured within the JSD retained proteoglycans significantly better than those cultured in static culture. Maintenance of cartilage specimens in a JSD was highly effective in keeping the vitality of cartilage explants in vitro over a 10-day period. A possible future

  12. Showing Value (Editorial

    Directory of Open Access Journals (Sweden)

    Denise Koufogiannakis

    2009-06-01

    librarians on student achievement. Todd notes, “If we do not show value, we will not have a future. Evidence-based practice is not about the survival of school librarians, it’s about the survival of our students” (40. In this issue we feature school libraries and their connection to evidence based practice. Former Editor-in-Chief, Lindsay Glynn, began putting the wheels in motion for this feature almost a year ago. She invited Carol Gordon and Ross Todd to act as guest editors of the section, drawing upon their contacts and previous work in this field. The result is an issue with five feature articles exploring different aspects of the connection between school libraries and evidence based practice, from the theoretical to the practical. In addition, there is a thought-provoking Commentary by David Loertscher, asking whether we need the evolutionary model of evidence based practice, or something more revolutionary!In addition to the Feature section, we have a well-rounded issue with articles on the topics of library human resources, and the development of a scholars’ portal. As well, there are a record 10 evidence summaries and our educational EBL101 column. I hope there is something for everyone in this issue of EBLIP – enjoy, and see you soon in Stockholm!

  13. Islet neogenesis potential of human adult stem cells and its applications in cell replacement therapy for diabetes

    Directory of Open Access Journals (Sweden)

    Bhonde RR

    2008-11-01

    Full Text Available In recent years regenerative biology has reached to greater heights due to its therapeutic potential in treating degenerative diseases; as they are not curable by modern medicine. With the advent of research in stem cells and developmental biology the regenerative potential of adult resident stem cells is becoming clearer. The long term objective of regenerative medicine or cell therapy is to treat patients with their own stem cells. These stem cells could be derived from the diseased organs such as skin, liver, pancreas etc. or from reservoirs of multipotent stem cells such as bone marrow or cord blood.Manipulating the ability of tissue resident stem cells as well as from multipotent reservoirs such as bone marrow, umbilical cord and cord blood to give rise to endocrine cells may open new avenues in the treatment of diabetes. A better understanding of stem cell biology would almost certainly allow for the establishment of efficient and reliable cell transplantation experimental programs in the clinic. We show here that multipotent mesenchymal stem cells can be isolated from various sources such as the bone marrow, placenta, umbilical cord. Upon stimulation with specific growth factors they differentiate into islet like clusters (ILCs. When ILCs obtained from the above mentioned sources were transplanted in experimental diabetic mice, restoration of normoglycemia was observed within three weeks of transplantation with concomitant increase in the body weight. These euglycemic mice exhibited normal glucose tolerance test indicating normal utilization of glucose. Allthough the MSCs isolated from all the sources had the same characteristics; they showed significant differences in their islet differentiation potential. ILCs isolated for the human bone marrow did not show any pancreatic hormones in vitro, but upon transplantation they matured into insulin and somatostatin producing hormones. Placental MSCs as well as ILCs showed insulin trascripts

  14. Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs.

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    Federica Collino

    Full Text Available BACKGROUND: Cell-derived microvesicles (MVs have been described as a new mechanism of cell-to-cell communication. MVs after internalization within target cells may deliver genetic information. Human bone marrow derived mesenchymal stem cells (MSCs and liver resident stem cells (HLSCs were shown to release MVs shuttling functional mRNAs. The aim of the present study was to evaluate whether MVs derived from MSCs and HLSCs contained selected micro-RNAs (miRNAs. METHODOLOGY/PRINCIPAL FINDINGS: MVs were isolated from MSCs and HLSCs. The presence in MVs of selected ribonucleoproteins involved in the traffic and stabilization of RNA was evaluated. We observed that MVs contained TIA, TIAR and HuR multifunctional proteins expressed in nuclei and stress granules, Stau1 and 2 implicated in the transport and stability of mRNA and Ago2 involved in miRNA transport and processing. RNA extracted from MVs and cells of origin was profiled for 365 known human mature miRNAs by real time PCR. Hierarchical clustering and similarity analysis of miRNAs showed 41 co-expressed miRNAs in MVs and cells. Some miRNAs were accumulated within MVs and absent in the cells after MV release; others were retained within the cells and not secreted in MVs. Gene ontology analysis of predicted and validated targets showed that the high expressed miRNAs in cells and MVs could be involved in multi-organ development, cell survival and differentiation. Few selected miRNAs shuttled by MVs were also associated with the immune system regulation. The highly expressed miRNAs in MVs were transferred to target cells after MV incorporation. CONCLUSIONS: This study demonstrated that MVs contained ribonucleoproteins involved in the intracellular traffic of RNA and selected pattern of miRNAs, suggesting a dynamic regulation of RNA compartmentalization in MVs. The observation that MV-highly expressed miRNAs were transferred to target cells, rises the possibility that the biological effect of stem

  15. Improved function and proliferation of adult human beta cells engrafted in diabetic immunodeficient NOD-scid IL2rγnull mice treated with alogliptin

    Directory of Open Access Journals (Sweden)

    Jurczyk A

    2013-12-01

    Full Text Available Agata Jurczyk,1 Philip diIorio,1 Dean Brostowin,1 Linda Leehy,1 Chaoxing Yang,1 Fumihiko Urano,2 David M Harlan,3 Leonard D Shultz,4 Dale L Greiner,1 Rita Bortell1 1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 2Department of Medicine, Washington University School of Medicine, St Louis, MO, 3Department of Medicine, University of Massachusetts Medical School, Worcester, MA, 4The Jackson Laboratory, Bar Harbor, ME, USA Purpose: Dipeptidyl-peptidase-4 (DPP-4 inhibitors are known to increase insulin secretion and beta cell proliferation in rodents. To investigate the effects on human beta cells in vivo, we utilize immunodeficient mice transplanted with human islets. The study goal was to determine the efficacy of alogliptin, a DPP-4 inhibitor, to enhance human beta cell function and proliferation in an in vivo context using diabetic immunodeficient mice engrafted with human pancreatic islets. Methods: Streptozotocin-induced diabetic NOD-scid IL2rγnull (NSG mice were transplanted with adult human islets in three separate trials. Transplanted mice were treated daily by gavage with alogliptin (30 mg/kg/day or vehicle control. Islet graft function was compared using glucose tolerance tests and non-fasting plasma levels of human insulin and C-peptide; beta cell proliferation was determined by bromodeoxyuridine (BrdU incorporation. Results: Glucose tolerance tests were significantly improved by alogliptin treatment for mice transplanted with islets from two of the three human islet donors. Islet-engrafted mice treated with alogliptin also had significantly higher plasma levels of human insulin and C-peptide compared to vehicle controls. The percentage of insulin+BrdU+ cells in human islet grafts from alogliptin-treated mice was approximately 10-fold more than from vehicle control mice, consistent with a significant increase in human beta cell proliferation. Conclusion: Human islet-engrafted immunodeficient mice

  16. The impact of Body Worlds on adult visitors' knowledge on human anatomy: A preliminary study.

    Science.gov (United States)

    Fonseca, Guilherme R B C; Finn, Gabrielle M

    2016-05-01

    Body Worlds is an anatomical exhibition that shows human remains to the public. It has been considered controversial since it raises ethical tensions and issues. However, organizers and supporters of Body Worlds have claimed the exhibition is intended to promote visitors' understanding over the human body. Despite these claims, no studies were found that support or refute the hypothesis that a visit to Body Worlds increases the public's objective knowledge on human anatomy. Consequently, the objective of this study was to determine the impact of Body Worlds on anatomical knowledge. We constructed and delivered a questionnaire to both a previsit random sample and a postvisit random sample of visitors of Body Worlds' event Facets of Life, in Berlin. The questionnaire was available in both English and German languages and contained (a) basic sociodemographic questions and (b) a valid and reliable anatomy quiz. The quiz consisted of 16 multiple-choice questions that assessed the ability to identify the location of major anatomical structures on the human body. Average scores achieved on the quiz by the postvisit sample (X¯= 9.08, s = 2.48, n = 164) were significantly higher (unpaired t = 3.3957, P = 0.0008) than those achieved by the previsit sample (X¯= 8.11, s = 2.69, n = 167). Our results suggest that a visit to Body Worlds' event Facets of Life may have a beneficial effect in anatomical knowledge. However, further studies with better empirical designs and fewer limitations are needed to confirm our results. © 2016 Wiley Periodicals, Inc.

  17. Foetal and adult human CYP3A isoforms in the bioactivation of organophosphorothionate insecticides.

    Science.gov (United States)

    Buratti, Franca M; Leoni, Claudia; Testai, Emanuela

    2006-12-15

    In humans organophosphorothionate pesticides (OPT) prenatal exposure has been demonstrated. Since OPT-induced neurodevelopmental effects may be due to in situ bioactivation by foetal enzymes, the catalytic activity of the foetal CYP3A7 toward chlorpyrifos (CPF), parathion (PAR), malathion (MAL) and fenthion (FEN) has been assessed by using recombinant enzymes. A comparison with the adult isoforms CYP3A4 and CYP3A5 has been also carried out. CYP3A7 was able to produce significant levels of oxon or sulfoxide from the four OPTs in the range of tested concentrations (0.05-200 microM). When the efficiencies of CYP3A isoforms were compared, the ranking, expressed as CLi values, were: CPF=3A4>3A5>3A7; PAR=3A4>3A7>3A5; MAL=3A4>3A7>3A5; FEN (sulfoxide formation)=3A4>3A5>3A7. The CYP3A5 efficiency appeared to be more dependent on the single insecticide than its related isozyme CYP3A4. Our results indicate that the levels of toxic metabolite formed in situ by CYP3A7 from CPF, MAL and PAR but not from FEN have the chance to inhibit acetylcholinesterase, following prenatal exposure to OPTs. However, due to the smaller weight of foetal liver, the contribution to total OPT biotransformation is relatively low. On the other hand, our results clearly indicate that at low CPF concentrations, the formation of the non-toxic metabolites is highly favoured in the foetus.

  18. Applied anatomic study of testicular veins in adult cadavers and in human fetuses

    Directory of Open Access Journals (Sweden)

    Luciano A. Favorito

    2007-04-01

    Full Text Available OBJECTIVES: Analyze the anatomic variations of the testicular veins in human cadavers and fetuses. MATERIALS AND METHODS: One hundred male adult cadavers and 24 fetuses were studied. Four anatomic aspects were considered: 1 Number of testicular veins, 2 The local of vein termination, 3 Type and number of collaterals present and 4 Testicular vein termination angle. RESULTS: Cadavers - Right side - One testicular vein occurred in 85% and 2 veins in 5% of the cases. There were communicating veins with the colon in 21% of the cases. Left side - One testicular vein occurred in 82%, two veins in 15%, three veins in 2% and four veins in 1% of the cases. There were communicating veins with the colon in 31% of the cases. Fetuses - Right side -One testicular vein occurred in all cases. This vein drained to the vena cava in 83.3% of the cases, to the junction of the vena cava with the renal vein in 12.5% and to the renal vein in 4.2%. There were communicating veins with the colon in 25% of the cases. Left side - One testicular vein occurred in 66.6% of the cases, and 2 veins in occurred 33.3%. Communicating veins with the colon were found in 41.6% of the cases. CONCLUSION: The testicular vein presents numeric variations and also variations in its local of termination. In approximately 30% of the cases, there are collaterals that communicate the testicular vein with retroperitoneal veins. These anatomic findings can help understanding the origin of varicocele and its recurrence after surgical interventions.

  19. The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration.

    Science.gov (United States)

    Umigai, N; Murakami, K; Ulit, M V; Antonio, L S; Shirotori, M; Morikawa, H; Nakano, T

    2011-05-15

    Crocetin, a unique carotenoid with a short carbon chain length, is an active compound of saffron and Gardenia jasminoides Ellis used as traditional herbal medicine. The present study was undertaken to investigate the pharmacokinetic profiles of crocetin in healthy adult subjects. The study was conducted as an open-label, single dose escalation with 10 Filipino volunteers (5 men and 5 women). The subjects received a single dose of crocetin at three doses (7.5, 15 and 22.5 mg) in one week interval. Blood samples were collected from the brachial vein before and at 1, 2, 4, 6, 8, 10 and 24 h after administration. Plasma concentrations of crocetin were determined by high-performance liquid chromatography (HPLC). Crocetin was rapidly absorbed and detected within an hour of administration with a mean time to reach maximum concentration (T(max)) of crocetin ranging from 4.0 to 4.8 h. The mean values of C(max) and AUC(0-24h) ranged from 100.9 to 279.7 ng/ml and 556.5 to 1720.8 ng. h/ml respectively. C(max) and AUC values increased with dose proportional manner. Crocetin was eliminated from human plasma with a mean elimination half life (T(½) of 6.1 to 7.5 h. In summary, there were no serious adverse events up to 22.5 mg dose of crocetin while crocetin was found to be absorbed more quickly than the other carotenoids such as β-carotene, lutein and lycopene. Copyright © 2010 Elsevier GmbH. All rights reserved.

  20. Sulcal pattern, extension, and morphology of the precuneus in adult humans.

    Science.gov (United States)

    Pereira-Pedro, Ana Sofia; Bruner, Emiliano

    2016-11-01

    The precuneus represents a relevant cortical component of the parietal lobes. It is involved in visuospatial integration, imagery and simulation, self-awareness, and it is a main node of the Default Mode Network. Its morphology is extremely variable among adult humans, and it has been hypothesized to have undergone major morphological changes in the evolution of Homo sapiens. Recent studies have evidenced a marked variation also associated with its sulcal patterns. The present survey contributes to add further information on this topic, investigating the extension of its main folds, their geometrical influence on the lateral parietal areas, and the relationships with the sulcal schemes. The subparietal sulcus, on average, extends 14mm in its anterior and middle regions and 11mm in its posterior area. The precuneal area extends 36mm above this sulcus. The subparietal sulcus is generally wider on the right hemisphere. Males have larger values than females, but differences are not significant. Sulcal pattern is not correlated with the size of the subparietal sulcus extension. There is a lack of consistent correspondence between hemispheres in the sulcal patterns, pointing further towards a notable individual variability and random asymmetries. The vertical extension of the precuneus influences the height and proportions of the upper parietal profile, but the lateral parietal outline is not sensitive to precuneal variation. There is no correlation between external cortical shape and the size of the subparietal sulcus. Morphological analyses of the precuneus must be integrated with studies on histological factors involved in its variability and, ultimately, with analyses on possible relationships with functional factors. Copyright © 2016 Elsevier GmbH. All rights reserved.

  1. Nanosized fibers' effect on adult human articular chondrocytes behavior

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-for-gestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA.

    Science.gov (United States)

    Audí, Laura; Esteban, Cristina; Carrascosa, Antonio; Espadero, Rosa; Pérez-Arroyo, Annalisa; Arjona, Rosa; Clemente, María; Wollmann, Hartmut; Fryklund, Linda; Parodi, Luis A

    2006-12-01

    A polymorphism in the human GH receptor gene (d3/fl-GHR) resulting in genomic deletion of exon 3 has been associated with the degree of height increase in response to GH therapy. The objective of the study was to evaluate the frequencies of d3/fl-GHR polymorphism genotypes in control and short small-for-gestational-age (SGA) populations. An adult control population with heights normally distributed (ACPNH) between -2 and +2 sd score (SDS) and a short non-GH-deficient SGA child population were selected. Thirty Spanish hospitals participated in the selection of the short non-GH-deficient SGA children in the setting of a controlled, randomized trial, and one of these hospitals selected the ACPNH. CONTROLS AND PATIENTS: Two hundred eighty-nine adult subjects of both sexes constituted the ACPNH and 247 children and adolescents of both sexes the short SGA patients. Heights and weights were recorded in the ACPNH, and auxologic and biochemical data were recorded at each hospital for the SGA patients; d3/fl-GHR genotypes were determined and data analyzed in a single hospital. In short SGA patients, d3/fl-GHR genotype frequencies were significantly different from those in ACPNH, with a higher frequency of fl/fl genotype (P or=-2 SDS, n = 60). Our data showed significant differences in the frequency distribution of the d3/fl-GHR genotypes between a normally distributed adult height population and short SGA children, with the biologically less active fl/fl genotype being almost twice as frequent in SGA patients. These data suggest that the d3/fl-GHR polymorphism might be considered among the factors that contribute to the phenotypic expression of growth.

  3. 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…

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Show-Bix &

    DEFF Research Database (Denmark)

    2014-01-01

    The anti-reenactment 'Show-Bix &' consists of 5 dias projectors, a dial phone, quintophonic sound, and interactive elements. A responsive interface will enable the Dias projectors to show copies of original dias slides from the Show-Bix piece ”March på Stedet”, 265 images in total. The copies are...

  7. Reactivating Fetal Hemoglobin Expression in Human Adult Erythroblasts Through BCL11A Knockdown Using Targeted Endonucleases

    Directory of Open Access Journals (Sweden)

    Carmen F Bjurström

    2016-01-01

    Full Text Available We examined the efficiency, specificity, and mutational signatures of zinc finger nucleases (ZFNs, transcriptional activator-like effector nucleases (TALENs, and clustered regularly interspaced short palindromic repeat (CRISPR/Cas9 systems designed to target the gene encoding the transcriptional repressor BCL11A, in human K562 cells and human CD34+ progenitor cells. ZFNs and TALENs were delivered as in vitro transcribed mRNA through electroporation; CRISPR/Cas9 was codelivered by Cas9 mRNA with plasmid-encoded guideRNA (gRNA (pU6.g1 or in vitro transcribed gRNA (gR.1. Analyses of efficacy revealed that for these specific reagents and the delivery methods used, the ZFNs gave rise to more allelic disruption in the targeted locus compared to the TALENs and CRISPR/Cas9, which was associated with increased levels of fetal hemoglobin in erythroid cells produced in vitro from nuclease-treated CD34+ cells. Genome-wide analysis to evaluate the specificity of the nucleases revealed high specificity of this specific ZFN to the target site, while specific TALENs and CRISPRs evaluated showed off-target cleavage activity. ZFN gene-edited CD34+ cells had the capacity to engraft in NOD-PrkdcSCID-IL2Rγnull mice, while retaining multi-lineage potential, in contrast to TALEN gene-edited CD34+ cells. CRISPR engraftment levels mirrored the increased relative plasmid-mediated toxicity of pU6.g1/Cas9 in hematopoietic stem/progenitor cells (HSPCs, highlighting the value for the further improvements of CRISPR/Cas9 delivery in primary human HSPCs.

  8. How Does Adult Attachment Affect Human Recognition of Love-related and Sex-related Stimuli: An ERP Study

    Science.gov (United States)

    Hou, Juan; Chen, Xin; Liu, Jinqun; Yao, Fangshu; Huang, Jiani; Ndasauka, Yamikani; Ma, Ru; Zhang, Yuting; Lan, Jing; Liu, Lu; Fang, Xiaoyi

    2016-01-01

    In the present study, we investigated the relationship among three emotion-motivation systems (adult attachment, romantic love, and sex). We recorded event-related potentials in 37 healthy volunteers who had experienced romantic love while they viewed SEX, LOVE, FRIEND, SPORT, and NEUTRAL images. We also measured adult attachment styles, level of passionate love and sexual attitudes. As expected, results showed that, firstly, response to love-related image-stimuli and sex-related image-stimuli on the electrophysiological data significantly different on N1, N2, and positive slow wave (PSW) components. Secondly, the different adult attachment styles affected individuals’ recognition processing in response to love-related and sex-related images, especially, to sex-related images. Further analysis showed that voltages elicited by fearful attachment style individuals were significantly lower than voltages elicited by secure and dismissing attachment style individuals on sex-related images at frontal sites, on N1 and N2 components. Thirdly, from behavior data, we found that adult attachment styles were not significantly related to any dimension of sexual attitudes but were significantly related to passionate love scale (PLS) total points. Thus, the behavior results were not in line with the electrophysiological results. The present study proved that adult attachment styles might mediate individuals’ lust and attraction systems. PMID:27199830

  9. Higher Prevalence of Human Papillomavirus Infection in Adolescent and Young Adult Girls Belonging to Different Indian Tribes with Varied Socio-Sexual Lifestyle

    Science.gov (United States)

    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

  10. 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

  11. 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.

  12. 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.

  13. Talking with TV shows

    DEFF Research Database (Denmark)

    Sandvik, Kjetil; Laursen, Ditte

    2014-01-01

    User interaction with radio and television programmes is not a new thing. However, with new cross-media production concepts such as X Factor and Voice, this is changing dramatically. The second-screen logic of these productions encourages viewers, along with TV’s traditional one-way communication...... mode, to communicate on interactive (dialogue-enabling) devices such as laptops, smartphones and tablets. Using the TV show Voice as our example, this article shows how the technological and situational set-up of the production invites viewers to engage in new ways of interaction and communication...

  14. Gene structure of CYP3A4, an adult-specific form of cytochrome P450 in human livers, and its transcriptional control.

    Science.gov (United States)

    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.

  15. Changes in radiation dose with variations in human anatomy: moderately and severely obese adults.

    Science.gov (United States)

    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.

  16. Human biomonitoring of phthalate exposure in Austrian children and adults and cumulative risk assessment.

    Science.gov (United States)

    Hartmann, Christina; Uhl, Maria; Weiss, Stefan; Koch, Holger M; Scharf, Sigrid; König, Jürgen

    2015-07-01

    children. The execution of a cumulative risk assessment based on Hazard Indices showed cause for concern mainly for children, as well as in rare cases for adults. Although phthalate exposure seems to have decreased in previous years, the wide distribution and existing exceedances of acceptable levels indicate that phthalate exposure should be further monitored in order to identify exposure sources and enable appropriate minimisation measures. Copyright © 2015 Elsevier GmbH. All rights reserved.

  17. Talk Show Science.

    Science.gov (United States)

    Moore, Mitzi Ruth

    1992-01-01

    Proposes having students perform skits in which they play the roles of the science concepts they are trying to understand. Provides the dialog for a skit in which hot and cold gas molecules are interviewed on a talk show to study how these properties affect wind, rain, and other weather phenomena. (MDH)

  18. Obesity in show cats.

    Science.gov (United States)

    Corbee, R J

    2014-12-01

    Obesity is an important disease with a high prevalence in cats. Because obesity is related to several other diseases, it is important to identify the population at risk. Several risk factors for obesity have been described in the literature. A higher incidence of obesity in certain cat breeds has been suggested. The aim of this study was to determine whether obesity occurs more often in certain breeds. The second aim was to relate the increased prevalence of obesity in certain breeds to the official standards of that breed. To this end, 268 cats of 22 different breeds investigated by determining their body condition score (BCS) on a nine-point scale by inspection and palpation, at two different cat shows. Overall, 45.5% of the show cats had a BCS > 5, and 4.5% of the show cats had a BCS > 7. There were significant differences between breeds, which could be related to the breed standards. Most overweight and obese cats were in the neutered group. It warrants firm discussions with breeders and cat show judges to come to different interpretations of the standards in order to prevent overweight conditions in certain breeds from being the standard of beauty. Neutering predisposes for obesity and requires early nutritional intervention to prevent obese conditions. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

  19. Honored Teacher Shows Commitment.

    Science.gov (United States)

    Ratte, Kathy

    1987-01-01

    Part of the acceptance speech of the 1985 National Council for the Social Studies Teacher of the Year, this article describes the censorship experience of this honored social studies teacher. The incident involved the showing of a videotape version of the feature film entitled "The Seduction of Joe Tynan." (JDH)

  20. 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)

  1. 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

  2. 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

  3. The energy show

    International Nuclear Information System (INIS)

    1988-01-01

    The Energy Show is a new look at the problems of world energy, where our supplies come from, now and in the future. The programme looks at how we need energy to maintain our standards of living. Energy supply is shown as the complicated set of problems it is - that Fossil Fuels are both raw materials and energy sources, that some 'alternatives' so readily suggested as practical options are in reality a long way from being effective. (author)

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994.

    Science.gov (United States)

    Jelenkovic, Aline; Hur, Yoon-Mi; Sund, Reijo; Yokoyama, Yoshie; Siribaddana, Sisira H; Hotopf, Matthew; Sumathipala, Athula; Rijsdijk, Fruhling; Tan, Qihua; Zhang, Dongfeng; Pang, Zengchang; Aaltonen, Sari; Heikkilä, Kauko; Öncel, Sevgi Y; Aliev, Fazil; Rebato, Esther; Tarnoki, Adam D; Tarnoki, David L; Christensen, Kaare; Skytthe, Axel; Kyvik, Kirsten O; Silberg, Judy L; Eaves, Lindon J; Maes, Hermine H; Cutler, Tessa L; Hopper, John L; Ordoñana, Juan R; Sánchez-Romera, Juan F; Colodro-Conde, Lucia; Cozen, Wendy; Hwang, Amie E; Mack, Thomas M; Sung, Joohon; Song, Yun-Mi; Yang, Sarah; Lee, Kayoung; Franz, Carol E; Kremen, William S; Lyons, Michael J; Busjahn, Andreas; Nelson, Tracy L; Whitfield, Keith E; Kandler, Christian; Jang, Kerry L; Gatz, Margaret; Butler, David A; Stazi, Maria A; Fagnani, Corrado; D'Ippolito, Cristina; Duncan, Glen E; Buchwald, Dedra; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth Jf; Martin, Nicholas G; Medland, Sarah E; Montgomery, Grant W; Jeong, Hoe-Uk; Swan, Gary E; Krasnow, Ruth; Magnusson, Patrik Ke; Pedersen, Nancy L; Dahl-Aslan, Anna K; McAdams, Tom A; Eley, Thalia C; Gregory, Alice M; Tynelius, Per; Baker, Laura A; Tuvblad, Catherine; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Lichtenstein, Paul; Spector, Timothy D; Mangino, Massimo; Lachance, Genevieve; Bartels, Meike; van Beijsterveldt, Toos Cem; Willemsen, Gonneke; Burt, S Alexandra; Klump, Kelly L; Harris, Jennifer R; Brandt, Ingunn; Nilsen, Thomas Sevenius; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Corley, Robin P; Hjelmborg, Jacob V B; Goldberg, Jack H; Iwatani, Yoshinori; Watanabe, Mikio; Honda, Chika; Inui, Fujio; Rasmussen, Finn; Huibregtse, Brooke M; Boomsma, Dorret I; Sørensen, Thorkild I A; Kaprio, Jaakko; Silventoinen, Karri

    2016-12-14

    Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.

  6. The breaking and making of healthy adult human skeletal muscle in vivo

    DEFF Research Database (Denmark)

    Mackey, Abigail L.; Kjaer, Michael

    2017-01-01

    and highlights the importance of the basement membrane in the process of regeneration. In addition, it provides insight into parallels between the regeneration of adult skeletal muscle in mouse and man, confirming that this model may be a useful tool in investigating myofibre and matrix formation, as well...

  7. Mass Entertainment and Human Survival: Television's Potential for Prosocial Effects on Adults.

    Science.gov (United States)

    Loye, David

    Psychosocial adaptations are sometimes affected by experiences that are ordinarily considered to be amusements. In 1974, a field study was undertaken by the Program on Psychosocial Adaptation and the Future to determine if it is possible to measure the effect of television on adult viewers. A sample of 260 couples, controlled for demographic…

  8. Hiding and Searching Strategies of Adult Humans in a Virtual and a Real-Space Room

    Science.gov (United States)

    Talbot, Katherine J.; Legge, Eric L. G.; Bulitko, Vadim; Spetch, Marcia L.

    2009-01-01

    Adults searched for or cached three objects in nine hiding locations in a virtual room or a real-space room. In both rooms, the locations selected by participants differed systematically between searching and hiding. Specifically, participants moved farther from origin and dispersed their choices more when hiding objects than when searching for…

  9. Adult Education as a Human Right: The Latin American Context and the Ecopedagogic Perspective

    Science.gov (United States)

    Gadotti, Moacir

    2011-01-01

    This article presents the concept and practice of adult education as a key issue for Brazil and other Latin American countries, both for formal and non-formal education in the public and private sectors. It includes citizen education focused on democratisation of society and sustainable development. The concept is pluralist and ideological as well…

  10. 21st Century African Philosophy of Adult and Human Resource Education in Southern Africa

    Science.gov (United States)

    Mutamba, Charlene

    2012-01-01

    This paper will attempt to define a philosophy of adult education for the purpose of workforce development in Southern Africa. The different influences such as Ubuntu and communalism, indigenous education, diversity western philosophy, globalization and technology are explored in the context of the Southern African region.

  11. 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

  12. Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells

    NARCIS (Netherlands)

    Forster, Ryan; Chiba, Kunitoshi; Schaeffer, Lorian; Regalado, Samuel G; Lai, Christine S; Gao, Qing; Kiani, Samira; Farin, Henner F; Clevers, Hans; Cost, Gregory J; Chan, Andy; Rebar, Edward J; Urnov, Fyodor D; Gregory, Philip D; Pachter, Lior; Jaenisch, Rudolf; Hockemeyer, Dirk

    2014-01-01

    Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  16. Preservation of beta cell function in adult human pancreatic islets for several months in vitro

    DEFF Research Database (Denmark)

    Brunstedt, J; Andersson, A; Frimodt-Møller, C

    1979-01-01

    Islets of Langerhans were isolated from four human kidney donors, aged 16 to 21 years by the collagenase method described for isolation of rodent islets. So far the human islets have been kept in tissue culture, without attachment, in medium RPMI 1640 supplemented with 10% calf serum for more tha...... technique presents a valuable tool for studying chronic effects of metabolites and hormones on islet function, as well as for islet storage prior to transplantation into humans.......Islets of Langerhans were isolated from four human kidney donors, aged 16 to 21 years by the collagenase method described for isolation of rodent islets. So far the human islets have been kept in tissue culture, without attachment, in medium RPMI 1640 supplemented with 10% calf serum for more than...

  17. 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

  18. 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...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Changes in radiation dose with variations in human anatomy: larger and smaller normal-stature adults.

    Science.gov (United States)

    Marine, Patrick M; Stabin, Michael G; Fernald, Michael J; Brill, Aaron B

    2010-05-01

    A systematic evaluation has been performed to study how specific absorbed fractions (SAFs) vary with changes in adult body size, for persons of different size but normal body stature. A review of the literature was performed to evaluate how individual organ sizes vary with changes in total body weight of normal-stature individuals. On the basis of this literature review, changes were made to our easily deformable reference adult male and female total-body models. Monte Carlo simulations of radiation transport were performed; SAFs for photons were generated for 10th, 25th, 75th, and 90th percentile adults; and comparisons were made to the reference (50th) percentile SAF values. Differences in SAFs for organs irradiating themselves were between 0.5% and 1.0%/kg difference in body weight, from 15% to 30% overall, for organs within the trunk. Differences in SAFs for organs outside the trunk were not greater than the uncertainties in the data and will not be important enough to change calculated doses. For organs irradiating other organs within the trunk, differences were significant, between 0.3% and 1.1%/kg, or about 8%-33% overall. The differences are interesting and can be used to estimate how different patients' dosimetry might vary from values reported in standard dose tables.

  4. Multisite recruitment and data collection among older adults: exploring methods to conserve human and financial resources.

    Science.gov (United States)

    McCarthy, Valerie Lander; Cassidy, Karen

    2012-01-01

    The purpose of this article is to describe strategies that were effective in recruitment and data collection among older adults in 3 quantitative studies while decreasing costs in terms of time and money. Factors effective in reducing use of investigators' time and expenses included limiting exclusion of data because of abnormal Mini-Cog scores by careful initial screening and avoiding repeated reminders or follow-up, collecting data in small groups, collapsing consent, dementia screening, and data collection into single sessions, as well as accommodating for sensory and literacy deficits. The cross-sectional, descriptive studies were conducted among community-dwelling older adults attending senior citizen centers and among older adults in independent or assisted living apartments within continuing care retirement communities (CCRCs). In the latest study, a convenience sample (N=152) was recruited and data collection was completed in 4 weeks at a total cost of less than $5,000. Methods common to qualitative research and those commonly used in community-based research were adapted to reduce time and costs for recruitment, screening, and data collection. Given limited availability of research funding, other nursing researchers may find one or more of these methods useful.

  5. A Western diet ecological module identified from the 'humanized' mouse microbiota predicts diet in adults and formula feeding in children.

    Science.gov (United States)

    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.

  6. 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.

  7. Hepatitis B virus infection in human immunodeficiency virus infected southern African adults: occult or overt--that is the question.

    Directory of Open Access Journals (Sweden)

    Trevor G Bell

    Full Text Available Hepatitis B virus (HBV and human immunodeficiency virus (HIV share transmission routes and are endemic in sub-Saharan Africa. The objective of the present study was to use the Taormina definition of occult HBV infection, together with stringent amplification conditions, to determine the prevalence and characteristics of HBV infection in antiretroviral treatment (ART-naïve HIV(+ve adults in a rural cohort in South Africa. The presence of HBV serological markers was determined by enzyme linked immunoassay (ELISA tests. HBV DNA-positivity was determined by polymerase chain reaction (PCR of at least two of three different regions of the HBV genome. HBV viral loads were determined by real-time PCR. Liver fibrosis was determined using the aspartate aminotransferase-to-platelet ratio index. Of the 298 participants, 231 (77.5% showed at least one HBV marker, with 53.7% HBV DNA(-ve (resolved and 23.8% HBV DNA(+ve (current [8.7% HBsAg(+ve: 15.1% HBsAg(-ve]. Only the total number of sexual partners distinguished HBV DNA(+ve and HBV DNA(-ve participants, implicating sexual transmission of HBV and/or HIV. It is plausible that sexual transmission of HBV and/or HIV may result in a new HBV infection, superinfection and re-activation as a consequence of immunesuppression. Three HBsAg(-ve HBV DNA(+ve participants had HBV viral loads <200 IU/ml and were therefore true occult HBV infections. The majority of HBsAg(-ve HBV DNA(+ve participants did not differ from HBsAg(+ve HBV DNA(+ve (overt participants in terms of HBV viral loads, ALT levels or frequency of liver fibrosis. Close to a quarter of HIV(+ve participants were HBV DNA(+ve, of which the majority were HBsAg(-ve and were only detected using nucleic acid testing. Detection of HBsAg(-ve HBV DNA(+ve subjects is advisable considering they were clinically indistinguishable from HBsAg(+ve HBV DNA(+ve individuals and should not be overlooked, especially if lamivudine is included in the ART.

  8. Polysialylated-neural cell adhesion molecule (PSA-NCAM in the human trigeminal ganglion and brainstem at prenatal and adult ages

    Directory of Open Access Journals (Sweden)

    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

  9. Human Milk Shows Immunological Advantages Over Organic Milk Samples For Infants in the Presence of Lipopolysaccharide (LPS in 3D Energy Maps Using an Organic Nanobiomimetic Memristor/Memcapacitor

    Directory of Open Access Journals (Sweden)

    S-H. DUH

    2016-08-01

    Full Text Available Human milk is well known for its immunological advantages of protection and support for healthy early childhood cognitive development and prevention of chronic diseases over cow milk for infants. However, little is known about how the immunological advantages are linked to reduce Pathological High Frequency Oscillation (pHFO regarding neural synapse net energy outcomes when lipopolysaccharide (LPS attacks at a clinical concentration range compared with that in cow milk in a 3D energy map. We developed a nanostructure biomimetic memristor/memcapacitor device with a dual function of chronoamperometric (CA sensing/voltage sensing for the direct quantitative evaluation of immunological advantages between human milk and organic cow milk for infants in the presence of wide LPS concentration ranges; those ranges were between 5.0 pg/mL to 500 ng/mL and from 50 ng/mL to 1 µg/mL for both a CA and a voltage method, respectively. The Detection of Limit (DOL results are as follows: 3.73×10-18 g LPS vs. 1.2×10-16 g LPS in 40 µL milk samples using the 3.11×10-7cm3 voltage sensor and the 0.031cm2 CA sensor, respectively, under antibody-free and reagent-free conditions. The 3D energy map results show that cow milk is ten-times more prone to E. Coli attack, and the positive link was revealed that Pathological High Frequency Oscillation (pHFO formations occurred over the studied LPS concentration range from 50 ng/mL up to 1000 ng/mL from Rapid Eye Movement (REM sleep frequency, fast gamma frequency to Sharp Wave-Ripple Complexes (SPW- R frequency. There had no pHFO with human milk samples at Slow Wave Sleeping (SWS, REM and SPW- R frequencies. The microbiota in the human milk samples successfully overcame the endotoxin attack from E. coli bacteria, however the pHFO only occurred at fast gamma frequency linked with the LPS level ≥ 500 ng/mL. Organic milk samples show an order of magnitude lower synapse energy density compared with human milk at SWS for with

  10. Adult hippocampal neurogenesis reduces memory interference in humans: opposing effects of aerobic exercise and depression

    Directory of Open Access Journals (Sweden)

    Nicolas eDéry

    2013-04-01

    Full Text Available Since the remarkable discovery of adult neurogenesis in the mammalian hippocampus, considerable effort has been devoted to unraveling the functional significance of these new neurons. Our group has proposed that a continual turnover of neurons in the DG could contribute to the development of event-unique memory traces that act to reduce interference between highly similar inputs. To test this theory, we implemented a continuous recognition task containing some objects that were repeated across trials as well as some objects that were highly similar, but not identical, to ones previously observed. The similar objects, termed lures, overlap substantially with previously viewed stimuli, and thus, may require hippocampal neurogenesis in order to avoid catastrophic interference. Lifestyle factors such as aerobic exercise and stress have been shown to impact the local neurogenic microenvironment, leading to enhanced and reduced levels of DG neurogenesis, respectively. Accordingly, we hypothesized that healthy young adults who take part in a long-term aerobic exercise regime would demonstrate enhanced performance on the visual pattern separation task, specifically at correctly categorizing lures as similar. Indeed, those who experienced a proportionally large change in fitness demonstrated a significantly greater improvement in their ability to correctly identify lure stimuli as similar. Conversely, we expected that those who score high on depression scales, an indicator of chronic stress, would exhibit selective deficits at appropriately categorizing lures. As expected, those who scored high on the Beck Depression Inventory (BDI were significantly worse than those with relatively lower BDI scores at correctly identifying lures as similar, while performance on novel and repeated stimuli was identical. Taken together, our results support the hypothesis that adult-born neurons in the DG contribute to the orthogonalization of incoming information.

  11. 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.

  12. 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.

  13. 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

  14. Strategies for human-driven robot comprehension of spatial descriptions by older adults in a robot fetch task.

    Science.gov (United States)

    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.

  15. Surface Hydrophilicity of Poly(l-Lactide Acid Polymer Film Changes the Human Adult Adipose Stem Cell Architecture

    Directory of Open Access Journals (Sweden)

    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.

  16. Relationship between Human Gut Microbiota and Interleukin 6 Levels in Overweight and Obese Adults

    Science.gov (United States)

    Background: Gut microbial diversity and abundance can profoundly impact human health. Research has shown that obese individuals are likely to have altered microbiota compared to lean individuals. Obesity is often considered a pro-inflammatory state, however the relationship between microbiota and i...

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

    NARCIS (Netherlands)

    Becker, M.; Guadalupe, T.M.; Franke, B.; Hibar, D.P.; Renteria, M.E.; Stein, J.L.; Thompson, P.M.; Francks, C.; Vernes, S.C; Fisher, S.E.

    2016-01-01

    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

  18. Human recombinant protein C for severe sepsis and septic shock in adult and paediatric patients

    DEFF Research Database (Denmark)

    Martí-Carvajal, Arturo J; Solà, Ivan; Gluud, Christian

    2012-01-01

    Sepsis is a common and frequently fatal condition. Human recombinant activated protein C (APC) has been introduced to reduce the high risk of death associated with severe sepsis or septic shock. This systematic review is an update of a Cochrane review originally published in 2007....

  19. Examining the Relationship between Childhood Animal Cruelty Motives and Recurrent Adult Violent Crimes toward Humans

    Science.gov (United States)

    Overton, Joshua C.; Hensley, Christopher; Tallichet, Suzanne E.

    2012-01-01

    Few researchers have studied the predictive ability of childhood animal cruelty motives as they are associated with later recurrent violence toward humans. Based on a sample of 180 inmates at one medium- and one maximum-security prison in a Southern state, the present study examines the relationship among several retrospectively identified motives…

  20. Gene × Smoking Interactions on Human Brain Gene Expression: Finding Common Mechanisms in Adolescents and Adults

    Science.gov (United States)

    Wolock, Samuel L.; Yates, Andrew; Petrill, Stephen A.; Bohland, Jason W.; Blair, Clancy; Li, Ning; Machiraju, Raghu; Huang, Kun; Bartlett, Christopher W.

    2013-01-01

    Background: Numerous studies have examined gene × environment interactions (G × E) in cognitive and behavioral domains. However, these studies have been limited in that they have not been able to directly assess differential patterns of gene expression in the human brain. Here, we assessed G × E interactions using two publically available datasets…

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

    DEFF Research Database (Denmark)

    Wood, Andrew R.; Esko, Tonu; Yang, Jian

    2014-01-01

    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...

  2. Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

    DEFF Research Database (Denmark)

    Jelenkovic, Aline; Hur, Yoon-Mi; Sund, Reijo

    2016-01-01

    Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic...

  3. Diffusion tensor spectroscopic imaging of the human brain in children and adults.

    Science.gov (United States)

    Fotso, Kevin; Dager, Stephen R; Landow, Alec; Ackley, Elena; Myers, Orrin; Dixon, Mindy; Shaw, Dennis; Corrigan, Neva M; Posse, Stefan

    2017-10-01

    We developed diffusion tensor spectroscopic imaging (DTSI), based on proton-echo-planar-spectroscopic imaging (PEPSI), and evaluated the feasibility of mapping brain metabolite diffusion in adults and children. PRESS prelocalized DTSI at 3 Tesla (T) was performed using navigator-based correction of movement-related phase errors and cardiac gating with compensation for repetition time (TR) related variability in T 1 saturation. Mean diffusivity (MD) and fractional anisotropy (FA) of total N-acetyl-aspartate (tNAA), total creatine (tCr), and total choline (tCho) were measured in eight adults (17-60 years) and 10 children (3-24 months) using b max  = 1734 s/mm 2 , 1 cc and 4.5 cc voxel sizes, with nominal scan times of 17 min and 8:24 min. Residual movement-related phase encoding ghosting (PEG) was used as a regressor across scans to correct overestimation of MD. After correction for PEG, metabolite slice-averaged MD estimated at 20% PEG were lower (P < 0.042) for adults (0.17/0.20/0.18 × 10 -3 mm 2 /s) than for children (0.26/0.27/0.24 × 10 -3 mm 2 /s). Extrapolated to 0% PEG, the MD estimates decreased further (0.09/0.11/0.11 × 10 -3 mm 2 /s versus 0.15/0.16/0.15 × 10 -3 mm 2 /s). Slice-averaged FA of tNAA (P = 0.049), tCr (P = 0.067), and tCho (P = 0.003) were higher in children. This high-speed DTSI approach with PEG regression allows for estimation of metabolite MD and FA with improved tolerance to movement. Our preliminary data suggesting age-related changes support DTSI as a sensitive technique for investigating intracellular markers of biological processes. Magn Reson Med 78:1246-1256, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  4. Human Adult Stem Cells Maintain a Constant Phenotype Profile Irrespective of Their Origin, Basal Media, and Long Term Cultures

    Directory of Open Access Journals (Sweden)

    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.

  5. 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...

  6. 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.)

  7. Validation of case-finding algorithms derived from administrative data for identifying adults living with human immunodeficiency virus infection.

    Directory of Open Access Journals (Sweden)

    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.

  8. Angiotensin-converting enzyme (CD143) marks hematopoietic stem cells in human embryonic, fetal, and adult hematopoietic tissues

    NARCIS (Netherlands)

    Jokubaitis, Vanta J.; Sinka, Lidia; Driessen, Rebecca; Whitty, Genevieve; Haylock, David N.; Bertoncello, Ivan; Smith, Ian; Peault, Bruno; Tavian, Manuela; Simmons, Paul J.

    2008-01-01

    Previous studies revealed that mAb BB9 reacts with a subset of CD34(+) human BM cells with hematopoietic stem cell (HSC) characteristics. Here we map B89 expression throughout hernatopoietic development and show that the earliest definitive HSCs that arise at the ventral wall of the aorta and

  9. 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.

  10. Redifferentiation of insulin-secreting cells after in vitro expansion of adult human pancreatic islet tissue

    International Nuclear Information System (INIS)

    Lechner, Andreas; Nolan, Anna L.; Blacken, Robyn A.; Habener, Joel F.

    2005-01-01

    Cellular replacement therapy holds promise for the treatment of diabetes mellitus but donor tissue is severely limited. Therefore, we investigated whether insulin-secreting cells could be differentiated in vitro from a monolayer of cells expanded from human donor pancreatic islets. We describe a three-step culture protocol that allows for the efficient generation of insulin-producing cell clusters from in vitro expanded, hormone-negative cells. These clusters express insulin at levels of up to 34% that of average freshly isolated human islets and secrete C-peptide upon membrane depolarization. They also contain cells expressing the other major islet hormones (glucagon, somatostatin, and pancreatic polypeptide). The source of the newly differentiated endocrine cells could either be indigenous stem/progenitor cells or the proliferation-associated dedifferentiation and subsequent redifferentiation of mature endocrine cells. The in vitro generated cell clusters may be efficacious in providing islet-like tissue for transplantation into diabetic recipients

  11. Transgenic alfalfa plants co-expressing glutathione S-transferase (GST) and human CYP2E1 show enhanced resistance to mixed contaminates of heavy metals and organic pollutants

    International Nuclear Information System (INIS)

    Zhang, Yuanyuan; Liu, Junhong

    2011-01-01

    Transgenic alfalfa plants simultaneously expressing human CYP2E1 and glutathione S-transferase (GST) were generated from hypocotyl segments by the use of an Agrobacterium transformation system for the phytoremediation of the mixed contaminated soil with heavy metals and organic pollutants. The transgenic alfalfa plants were screened by a combination of kanamycin resistance, PCR, GST and CYP2E1 activity and Western blot analysis. The capabilities of mixed contaminants (heavy metals-organic compounds) resistance of pKHCG transgenic alfalfa plants became markedly increased compared with the transgenic alfalfa plants expressing single gene (GST or CYP2E1) and the non-transgenic control plants. The pKHCG alfalfa plants exhibited strong resistance towards the mixtures of cadmium (Cd) and trichloroethylene (TCE) that were metabolized by the introduced GST and CYP2E1 in combination. Our results show that the pKHCG transgenic alfalfa plants have good potential for phytoremediation because they have cross-tolerance towards the complex contaminants of heavy metals and organic pollutants. Therefore, these transgenic alfalfa plants co-expressing GST and human P450 CDNAs may have a great potential for phytoremediation of mixed environmental contaminants.

  12. Transgenic alfalfa plants co-expressing glutathione S-transferase (GST) and human CYP2E1 show enhanced resistance to mixed contaminates of heavy metals and organic pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yuanyuan [Department of Pharmaceutics, Qingdao University of Science and Technology, 53 Zhengzhou Road, P.O. Box 70, Qingdao 266042 (China); Liu, Junhong, E-mail: liujh@qust.edu.cn [Department of Pharmaceutics, Qingdao University of Science and Technology, 53 Zhengzhou Road, P.O. Box 70, Qingdao 266042 (China)

    2011-05-15

    Transgenic alfalfa plants simultaneously expressing human CYP2E1 and glutathione S-transferase (GST) were generated from hypocotyl segments by the use of an Agrobacterium transformation system for the phytoremediation of the mixed contaminated soil with heavy metals and organic pollutants. The transgenic alfalfa plants were screened by a combination of kanamycin resistance, PCR, GST and CYP2E1 activity and Western blot analysis. The capabilities of mixed contaminants (heavy metals-organic compounds) resistance of pKHCG transgenic alfalfa plants became markedly increased compared with the transgenic alfalfa plants expressing single gene (GST or CYP2E1) and the non-transgenic control plants. The pKHCG alfalfa plants exhibited strong resistance towards the mixtures of cadmium (Cd) and trichloroethylene (TCE) that were metabolized by the introduced GST and CYP2E1 in combination. Our results show that the pKHCG transgenic alfalfa plants have good potential for phytoremediation because they have cross-tolerance towards the complex contaminants of heavy metals and organic pollutants. Therefore, these transgenic alfalfa plants co-expressing GST and human P450 CDNAs may have a great potential for phytoremediation of mixed environmental contaminants.

  13. The polymorphic insertion of the luteinizing hormone receptor "insLQ" show a negative association to LHR gene expression and to the follicular fluid hormonal profile in human small antral follicles

    DEFF Research Database (Denmark)

    Borgbo, T; Chrudimska, J; Macek, M

    2018-01-01

    (AMHR2) and LHCGR, respectively, were observed for insLQ/insLQ compared to -/insLQ and the -/- genotypes. Moreover, LHCGR and CYP19a1 together with oestradiol and inhibin-B were significantly increased in -/insLQ compared to the -/- genotype. The homozygous insLQ genotype showed strong significant......The luteinizing hormone receptor (LHCGR) has a little studied polymorphic 6 bp insertion (rs4539842/insLQ). This study has evaluated the insLQ polymorphism in relation to potential associations with hormonal characteristics of human small antral follicles (hSAFs). In total, 310 hSAFs were collected...... from 86 women undergoing fertility preservation. Analysis included hormonal profile of 297 follicular fluid (FF) samples and 148 corresponding granulosa cells samples were evaluated by qPCR for selected genes. Significantly reduced and non-detectable mRNA levels of anti-Müllerian hormone receptor II...

  14. Effects of Moxa (Folium Artemisiae argyi Smoke Exposure on Heart Rate and Heart Rate Variability in Healthy Young Adults: A Randomized, Controlled Human Study

    Directory of Open Access Journals (Sweden)

    Yingxue Cui

    2013-01-01

    Full Text Available Objective. To determine the effects of the moxa smoke on human heart rate (HR and heart rate variability (HRV. Methods. Fifty-five healthy young adults were randomly divided into experimental (n=28 and control (n=27 groups. Experimental subjects were exposed to moxa smoke (2.5 ± 0.5 mg/m3 twice for 25 minutes in one week. ECG monitoring was performed before, during, and after exposure. Control subjects were exposed to normal indoor air in a similar environment and similarly monitored. Followup was performed the following week. Short-term (5 min HRV parameters were analyzed with HRV analysis software. SPSS software was used for statistical analysis. Results. During and after the first exposure, comparison of percentage changes or changes in all parameters between groups showed no significant differences. During the second exposure, percentage decrease in HR, percentage increases in lnTP, lnHF, lnLF, and RMSSD, and increase in PNN50 were significantly greater in the experimental group than in control. Conclusion. No significant adverse HRV effects were associated with this clinically routine 25-minute exposure to moxa smoke, and the data suggests that short-term exposure to moxa smoke might have positive regulating effects on human autonomic function. Further studies are warranted to confirm these findings.

  15. A Phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with imiglucerase.

    Science.gov (United States)

    Pastores, Gregory M; Petakov, Milan; Giraldo, Pilar; Rosenbaum, Hanna; Szer, Jeffrey; Deegan, Patrick B; Amato, Dominick J; Mengel, Eugen; Tan, Ee Shien; Chertkoff, Raul; Brill-Almon, Einat; Zimran, Ari

    2014-12-01

    Taliglucerase alfa is a β-glucosidase enzyme replacement therapy (ERT) approved in the US and other countries for the treatment of Gaucher disease (GD) in adults and is approved in pediatric and adult patients in Australia and Canada. It is the first approved plant cell-expressed recombinant human protein. A Phase 3, multicenter, open-label, 9-month study assessed safety and efficacy of switching to taliglucerase alfa in adult and pediatric patients with GD treated with imiglucerase for at least the previous 2years. Patients with stable disease were offered taliglucerase alfa treatment using the same dose (9-60U/kg body weight) and regimen of administration (every 2weeks) as imiglucerase. This report summarizes results from 26 adult and 5 pediatric patients who participated in the trial. Disease parameters (spleen and liver volumes, hemoglobin concentration, platelet count, and biomarker levels) remained stable through 9months of treatment in adults and children following the switch from imiglucerase. All treatment-related adverse events were mild or moderate in severity and transient in nature. Exploratory parameters of linear growth and development showed positive outcomes in pediatric patients. These findings provide evidence of the efficacy and safety profile of taliglucerase alfa as an ERT for GD in patients previously treated with imiglucerase. This trial was registered at www.clinicaltrials.gov as # NCT00712348. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. A Foxp2 mutation implicated in human speech deficits alters sequencing of ultrasonic vocalizations in adult male mice

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. Quantitative analysis of basal dendritic tree of layer III pyramidal neurons in different areas of adult human frontal cortex.

    Science.gov (United States)

    Zeba, Martina; Jovanov-Milosević, Natasa; Petanjek, Zdravko

    2008-01-01

    Large long projecting (cortico-cortical) layer IIIc pyramidal neurons were recently disclosed to be in the basis of cognitive processing in primates. Therefore, we quantitatively examined the basal dendritic morphology of these neurons by using rapid Golgi and Golgi Cox impregnation methods among three distinct Brodmann areas (BA) of an adult human frontal cortex: the primary motor BA4 and the associative magnopyramidal BA9 from left hemisphere and the Broca's speech BA45 from both hemispheres. There was no statistically significant difference in basal dendritic length or complexity, as dendritic spine number or their density between analyzed BA's. In addition, we analyzed each of these BA's immunocytochemically for distribution of SMI-32, a marker of largest long distance projecting neurons. Within layer IIIc, the highest density of SMI-32 immunopositive pyramidal neurons was observed in associative BA9, while in primary BA4 they were sparse. Taken together, these data suggest that an increase in the complexity of cortico-cortical network within human frontal areas of different functional order may be principally based on the increase in density of large, SMI-32 immunopositive layer IIIc neurons, rather than by further increase in complexity of their dendritic tree and synaptic network.

  19. Metabolic fate of dietary carnitine in human adults: Identification and quantification of urinary and fecal metabolites

    International Nuclear Information System (INIS)

    Rebouche, C.J.; Chenard, C.A.

    1991-01-01

    Results of kinetic and pharmacokinetic studies have suggested that dietary carnitine is not totally absorbed and is in part degraded in the gastrointestinal tract of humans. To determine the metabolic fate of dietary carnitine in humans, we administered orally a tracer dose of methyl- 3 H L-carnitine with a meal to subjects who had been adapted to a low-carnitine diet or a high-carnitine diet. Urinary and fecal excretion of radiolabeled carnitine and metabolites was monitored for 5 to 11 d following administration of the test dose. Total radioactive metabolites excreted ranged from 13 to 34% (low carnitine diet) and 27 to 46% (high carnitine diet) of the ingested tracer. Major metabolites found were [ 3 H]trimethylamine N-oxide (8 to 39% of the administered dose; excreted primarily in urine) and [ 3 H]gamma-butyrobetaine (0.09 to 8% of the administered dose; excreted primarily in feces). Urinary excretion of total carnitine was 42 to 95% (high carnitine diet) and 190 to 364% (low carnitine diet) of intake. These results indicate that oral carnitine is 54 to 87% bioavailable from normal Western diets; the percentage of intake absorbed is related to the quantity ingested

  20. Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution.

    Science.gov (United States)

    Hu, Wen-Yang; Hu, Dan-Ping; Xie, Lishi; Li, Ye; Majumdar, Shyama; Nonn, Larisa; Hu, Hong; Shioda, Toshi; Prins, Gail S

    2017-08-01

    Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers. Knockdown of KRT13 or PRAC1 reduced sphere formation and symmetric self-renewal highlighting their role in stem cell maintenance. Pathways analysis identified ribosome biogenesis and membrane estrogen-receptor signaling enriched in stem cells with NF-ĸB signaling enriched in progenitors; activities that were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution

    Directory of Open Access Journals (Sweden)

    Wen-Yang Hu

    2017-08-01

    Full Text Available Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers. Knockdown of KRT13 or PRAC1 reduced sphere formation and symmetric self-renewal highlighting their role in stem cell maintenance. Pathways analysis identified ribosome biogenesis and membrane estrogen-receptor signaling enriched in stem cells with NF-ĸB signaling enriched in progenitors; activities that were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland.

  2. Circle of willis and its variations; morphometric study in adult human cadavers

    Directory of Open Access Journals (Sweden)

    Raghavendra, Shirol VS, Daksha Dixit, Anil Kumar Reddy Y, Desai SP

    2014-04-01

    Full Text Available Background and Objectives: Circle of Willis plays a vital role in collateral circulation and redistribution of blood to all areas of the brain. Variation in circle of Willis is known to cause grave disorders like cerebrovascular disorders, subarachnoid haemorrhage, cerebral aneurysm and schizophrenia. The objectives of the present study are to study the formation and branching pattern of circle of Willis and also to study the distribution of variations. MATERIALS & Methods: The study was conducted on 50 adult brain specimens. Each brain was removed in one piece by dissection and the circle of Willis was observed for its formation, pattern and variations. Results: Among the 50 specimens studied, 28 cases (56% had a normal pattern of circle of Willis and variations were observed in the remaining 22 cases (44%. More number of variations was observed on the right side than on the left side. The most common variation observed was hypoplastic posterior communicating artery (7 cases, 31.8%. Posterior communicating artery was found to be the most variable vessel while middle cerebral artery was the least variable vessel. Interpretation and Conclusion: The results with respect to the circle of Willis and all its component arteries were consistent with the results in the available literature. The only exception was the increased incidence of absence of both the anterior and posterior communicating arteries. This finding is of clinical significance to neurologists and neurosurgeons in this geographical location of north Karnataka. A higher incidence of variations in the communicating arteries is likely to manifest as a higher incidence in disorders like migraine, schizophrenia and cerebrovascular disorders due to compromised collateral circulation and poor redistribution of blood.

  3. 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.

  4. Human rights violations and smoking status among South African adults enrolled in the South Africa Stress and Health (SASH) study.

    Science.gov (United States)

    Dutra, Lauren M; Williams, David R; Gupta, Jhumka; Kawachi, Ichiro; Okechukwu, Cassandra A

    2014-03-01

    Despite South Africa's history of violent political conflict, and the link between stressful experiences and smoking in the literature, no public health study has examined South Africans' experiences of human rights violations and smoking. Using data from participants in the nationally representative cross-sectional South Africa Stress and Health study (SASH), this analysis examined the association between respondent smoking status and both human rights violations experienced by the respondent and violations experienced by the respondents' close friends and family members. SAS-Callable SUDAAN was used to construct separate log-binomial models by political affiliation during apartheid (government or liberation supporters). In comparison to those who reported no violations, in adjusted analyses, government supporters who reported violations of themselves but not others (RR = 1.76, 95% CI: 1.25-2.46) had a significantly higher smoking prevalence. In comparison to liberation supporters who reported no violations, those who reported violations of self only (RR = 1.56, 95%CI: 1.07-2.29), close others only (RR = 1.97, 95%CI: 1.12-3.47), or violations of self and close others due to close others' political beliefs and the respondent's political beliefs (RR = 2.86, 95%CI: 1.70-4.82) had a significantly higher prevalence of smoking. The results of this analysis suggest that a relationship may exist between human rights violations and smoking among South Africa adults. Future research should use longitudinal data to assess causality, test the generalizability of these findings, and consider how to apply these findings to smoking cessation interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Improved nutrition in the first 1000 days and adult human capital and health.

    Science.gov (United States)

    Martorell, Reynaldo

    2017-03-01

    The aim of this article is to review why the first 1000 days of life are a vulnerable period of human development and the long-term effects of a nutrition experiment carried out in Guatemala (1969-1977). In 1969-77, a supplement called Atole, containing high quality protein, energy and micronutrients, was provided to women during pregnancy and lactation and to children nutritional requirements, greater susceptibility to infections, high sensitivity to programming effects and full dependence on others for care, nutrition, and social interaction. Compared with Fresco, Atole improved total nutrient intakes (protein, energy, and micronutrients) and reduced stunting, but only in children nutrition intervention. This provides a powerful argument for promoting improvements in nutrition in pregnant women and young children in low income countries. © 2017 Wiley Periodicals, Inc.

  6. Does the A-not-B error in adult pet dogs indicate sensitivity to human communication?

    Science.gov (United States)

    Kis, Anna; Topál, József; Gácsi, Márta; Range, Friederike; Huber, Ludwig; Miklósi, Adám; Virányi, Zsófia

    2012-07-01

    Recent dog-infant comparisons have indicated that the experimenter's communicative signals in object hide-and-search tasks increase the probability of perseverative (A-not-B) errors in both species (Topál et al. 2009). These behaviourally similar results, however, might reflect different mechanisms in dogs and in children. Similar errors may occur if the motor response of retrieving the object during the A trials cannot be inhibited in the B trials or if the experimenter's movements and signals toward the A hiding place in the B trials ('sham-baiting') distract the dogs' attention. In order to test these hypotheses, we tested dogs similarly to Topál et al. (2009) but eliminated the motor search in the A trials and 'sham-baiting' in the B trials. We found that neither an inability to inhibit previously rewarded motor response nor insufficiencies in their working memory and/or attention skills can explain dogs' erroneous choices. Further, we replicated the finding that dogs have a strong tendency to commit the A-not-B error after ostensive-communicative hiding and demonstrated the crucial effect of socio-communicative cues as the A-not-B error diminishes when location B is ostensively enhanced. These findings further support the hypothesis that the dogs' A-not-B error may reflect a special sensitivity to human communicative cues. Such object-hiding and search tasks provide a typical case for how susceptibility to human social signals could (mis)lead domestic dogs.

  7. Comparative Characterization of Cells from the Various Compartments of the Human Umbilical Cord Shows that the Wharton's Jelly Compartment Provides the Best Source of Clinically Utilizable Mesenchymal Stem Cells.

    Directory of Open Access Journals (Sweden)

    Arjunan Subramanian

    Full Text Available The human umbilical cord (UC is an attractive source of mesenchymal stem cells (MSCs with unique advantages over other MSC sources. They have been isolated from different compartments of the UC but there has been no rigorous comparison to identify the compartment with the best clinical utility. We compared the histology, fresh and cultured cell numbers, morphology, proliferation, viability, stemness characteristics and differentiation potential of cells from the amnion (AM, subamnion (SA, perivascular (PV, Wharton's jelly (WJ and mixed cord (MC of five UCs. The WJ occupied the largest area in the UC from which 4.61 ± 0.57 x 106 /cm fresh cells could be isolated without culture compared to AM, SA, PV and MC that required culture. The WJ and PV had significantly lesser CD40+ non-stem cell contaminants (26-27% compared to SA, AM and MC (51-70%. Cells from all compartments were proliferative, expressed the typical MSC-CD, HLA, and ESC markers, telomerase, had normal karyotypes and differentiated into adipocyte, chondrocyte and osteocyte lineages. The cells from WJ showed significantly greater CD24+ and CD108+ numbers and fluorescence intensities that discriminate between MSCs and non-stem cell mesenchymal cells, were negative for the fibroblast-specific and activating-proteins (FSP, FAP and showed greater osteogenic and chondrogenic differentiation potential compared to AM, SA, PV and MC. Cells from the WJ offer the best clinical utility as (i they have less non-stem cell contaminants (ii can be generated in large numbers with minimal culture avoiding changes in phenotype, (iii their derivation is quick and easy to standardize, (iv they are rich in stemness characteristics and (v have high differentiation potential. Our results show that when isolating MSCs from the UC, the WJ should be the preferred compartment, and a standardized method of derivation must be used so as to make meaningful comparisons of data between research groups.

  8. 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,

  9. 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...

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

    Science.gov (United States)

    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.

  11. Bilateral Transplantation of Allogenic Adult Human Bone Marrow-Derived Mesenchymal Stem Cells into the Subventricular Zone of Parkinson’s Disease: A Pilot Clinical Study

    Directory of Open Access Journals (Sweden)

    N. K. Venkataramana

    2012-01-01

    Full Text Available The progress of PD and its related disorders cannot be prevented with the medications available. In this study, we recruited 8 PD and 4 PD plus patients between 5 to 15 years after diagnosis. All patients received BM-MSCs bilaterally into the