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Sample records for elicits spontaneous human

  1. Children with Autism Respond Differently to Spontaneous, Elicited and Deferred Imitation

    ERIC Educational Resources Information Center

    Heimann, M.; Nordqvist, E.; Strid, K.; Connant Almrot, J.; Tjus, T.

    2016-01-01

    Background: Imitation, a key vehicle for both cognitive and social development, is often regarded as more difficult for children with autism spectrum disorders (ASD) than for children with Down syndrome (DS) or typically developing (TD) children. The current study investigates similarities and differences in observed elicited, spontaneous and…

  2. Mechanisms of spontaneous human cancers.

    PubMed

    Venitt, S

    1996-05-01

    The causes of much of human cancer remain obscure. The fraction that is spontaneous is unknown and cannot be calculated until all known external causes have been accounted for. This is not a feasible proposition. However, there is substantial evidence that about 80% of human cancer could be avoided by eliminating tobacco consumption; by dietary changes; by reducing infection with certain viruses, bacteria, and parasitic worms; and, in white populations, by avoiding sunburn. Alcohol, occupational and medical carcinogens, and certain patterns of reproductive behavior also contribute to the cancer burden. Cancers that cannot be attributed to these causes, and for which no other causes can be found, could be considered spontaneous and to arise from endogenous processes. Epidemiological evidence suggests that spontaneous and induced cancers share the same mechanism. Cancer is a genetic disorder of somatic cells. An accumulation of mutant genes that control the cell cycle, maintain genomic stability, and mediate apoptosis is central to carcinogenesis. Spontaneous mutation may cause spontaneous cancer. Endogenous causes of mutation include depurination and depyrimidation of DNA; proofreading and mismatch errors during DNA replication; deamination of 5-methylcytosine to produce C to T base pair substitutions; and damage to DNA and its replication imposed by products of metabolism (notably oxidative damage caused by oxygen free radicals). Deficiencies in cellular defense mechanisms may also provoke spontaneous mutation. These include defective DNA excision-repair; low levels of antioxidants, antioxidant enzymes, and nucleophiles that trap DNA-reactive electrophiles; and enzymes that conjugate nucleophiles with DNA-damaging electrophiles. Mechanisms underlying many of those cellular defenses are under genetic control. Thus, germ line mutations or polymorphisms of genes that govern them may also contribute to spontaneous cancer.

  3. Antagonist-elicited cannabis withdrawal in humans.

    PubMed

    Gorelick, David A; Goodwin, Robert S; Schwilke, Eugene; Schwope, David M; Darwin, William D; Kelly, Deanna L; McMahon, Robert P; Liu, Fang; Ortemann-Renon, Catherine; Bonnet, Denis; Huestis, Marilyn A

    2011-10-01

    Cannabinoid CB1 receptor antagonists have potential therapeutic benefits, but antagonist-elicited cannabis withdrawal has not been reported in humans. Ten male daily cannabis smokers received 8 days of increasingly frequent 20-mg oral Δ⁹-tetrahydrocannabinol (THC) dosages (40-120 mg/d) around-the-clock to standardize cannabis dependence while residing on a closed research unit. On the ninth day, double-blind placebo or 20- (suggested therapeutic dose) or 40-mg oral rimonabant, a CB1-cannabinoid receptor antagonist, was administered. Cannabis withdrawal signs and symptoms were assessed before and for 23.5 hours after rimonabant. Rimonabant, THC, and 11-hydroxy-THC plasma concentrations were quantified by mass spectrometry. The first 6 subjects received 20-mg rimonabant (1 placebo); the remaining 4 subjects received 40-mg rimonabant (1 placebo). Fourteen subjects enrolled; 10 completed before premature termination because of withdrawal of rimonabant from clinical development. Three of 5 subjects in the 20-mg group, 1 of 3 in the 40-mg group, and none of 2 in the placebo group met the prespecified withdrawal criterion of 150% increase or higher in at least 3 visual analog scales for cannabis withdrawal symptoms within 3 hours of rimonabant dosing. There were no significant associations between visual analog scale, heart rate, or blood pressure changes and peak rimonabant plasma concentration, area-under-the-rimonabant-concentration-by-time curve (0-8 hours), or peak rimonabant/THC or rimonabant/(THC + 11-hydroxy-THC) plasma concentration ratios. In summary, prespecified criteria for antagonist-elicited cannabis withdrawal were not observed at the 20- or 40-mg rimonabant doses. These data do not preclude antagonist-elicited withdrawal at higher rimonabant doses.

  4. Antagonist-elicited cannabis withdrawal in humans.

    PubMed

    Gorelick, David A; Goodwin, Robert S; Schwilke, Eugene; Schwope, David M; Darwin, William D; Kelly, Deanna L; McMahon, Robert P; Liu, Fang; Ortemann-Renon, Catherine; Bonnet, Denis; Huestis, Marilyn A

    2011-10-01

    Cannabinoid CB1 receptor antagonists have potential therapeutic benefits, but antagonist-elicited cannabis withdrawal has not been reported in humans. Ten male daily cannabis smokers received 8 days of increasingly frequent 20-mg oral Δ⁹-tetrahydrocannabinol (THC) dosages (40-120 mg/d) around-the-clock to standardize cannabis dependence while residing on a closed research unit. On the ninth day, double-blind placebo or 20- (suggested therapeutic dose) or 40-mg oral rimonabant, a CB1-cannabinoid receptor antagonist, was administered. Cannabis withdrawal signs and symptoms were assessed before and for 23.5 hours after rimonabant. Rimonabant, THC, and 11-hydroxy-THC plasma concentrations were quantified by mass spectrometry. The first 6 subjects received 20-mg rimonabant (1 placebo); the remaining 4 subjects received 40-mg rimonabant (1 placebo). Fourteen subjects enrolled; 10 completed before premature termination because of withdrawal of rimonabant from clinical development. Three of 5 subjects in the 20-mg group, 1 of 3 in the 40-mg group, and none of 2 in the placebo group met the prespecified withdrawal criterion of 150% increase or higher in at least 3 visual analog scales for cannabis withdrawal symptoms within 3 hours of rimonabant dosing. There were no significant associations between visual analog scale, heart rate, or blood pressure changes and peak rimonabant plasma concentration, area-under-the-rimonabant-concentration-by-time curve (0-8 hours), or peak rimonabant/THC or rimonabant/(THC + 11-hydroxy-THC) plasma concentration ratios. In summary, prespecified criteria for antagonist-elicited cannabis withdrawal were not observed at the 20- or 40-mg rimonabant doses. These data do not preclude antagonist-elicited withdrawal at higher rimonabant doses. PMID:21869692

  5. Exploring the Ecological Validity of Thinking on Demand: Neural Correlates of Elicited vs. Spontaneously Occurring Inner Speech

    PubMed Central

    Hurlburt, Russell T.; Alderson-Day, Ben

    2016-01-01

    Psychology and cognitive neuroscience often use standardized tasks to elicit particular experiences. We explore whether elicited experiences are similar to spontaneous experiences. In an MRI scanner, five participants performed tasks designed to elicit inner speech (covertly repeating experimenter-supplied words), inner seeing, inner hearing, feeling, and sensing. Then, in their natural environments, participants were trained in four days of random-beep-triggered Descriptive Experience Sampling (DES). They subsequently returned to the scanner for nine 25-min resting-state sessions; during each they received four DES beeps and described those moments (9 × 4 = 36 moments per participant) of spontaneously occurring experience. Enough of those moments included spontaneous inner speech to allow us to compare brain activation during spontaneous inner speech with what we had found in task-elicited inner speech. ROI analysis was used to compare activation in two relevant areas (Heschl’s gyrus and left inferior frontal gyrus). Task-elicited inner speech was associated with decreased activation in Heschl’s gyrus and increased activation in left inferior frontal gyrus. However, spontaneous inner speech had the opposite effect in Heschl’s gyrus and no significant effect in left inferior frontal gyrus. This study demonstrates how spontaneous phenomena can be investigated in MRI and calls into question the assumption that task-created phenomena are often neurophysiologically and psychologically similar to spontaneously occurring phenomena. PMID:26845028

  6. Brief Report: Pilot Randomized Controlled Trial of Reciprocal Imitation Training for Teaching Elicited and Spontaneous Imitation to Children with Autism

    PubMed Central

    Ingersoll, Brooke

    2013-01-01

    Children with autism exhibit significant deficits in imitation skills. Reciprocal Imitation Training (RIT), a naturalistic imitation intervention, was developed to teach young children with autism to imitate during play. This study used a randomized controlled trial to evaluate the efficacy of RIT on elicited and spontaneous imitation skills in 21 young children with autism. Results found that children in the treatment group made significantly more gains in elicited and spontaneous imitation, replicating previous single-subject design studies. Number of spontaneous play acts at pre-treatment was related to improvements in imitation during the intervention, suggesting that children with a greater play repertoire make greater gains during RIT. PMID:20155309

  7. Spontaneous perception of numerosity in humans

    PubMed Central

    Cicchini, Guido Marco; Anobile, Giovanni; Burr, David C.

    2016-01-01

    Humans, including infants, and many other species have a capacity for rapid, nonverbal estimation of numerosity. However, the mechanisms for number perception are still not clear; some maintain that the system calculates numerosity via density estimates—similar to those involved in texture—while others maintain that more direct, dedicated mechanisms are involved. Here we show that provided that items are not packed too densely, human subjects are far more sensitive to numerosity than to either density or area. In a two-dimensional space spanning density, area and numerosity, subjects spontaneously react with far greater sensitivity to changes in numerosity, than either area or density. Even in tasks where they were explicitly instructed to make density or area judgments, they responded spontaneously to number. We conclude, that humans extract number information, directly and spontaneously, via dedicated mechanisms. PMID:27555562

  8. Spontaneous human speech mimicry by a cetacean.

    PubMed

    Ridgway, Sam; Carder, Donald; Jeffries, Michelle; Todd, Mark

    2012-10-23

    Although dolphins (Tursiops truncatus) have been trained to match numbers and durations of human vocal bursts and reported to spontaneously match computer-generated whistles, spontaneous human voice mimicry has not previously been demonstrated. The first to study white whale (Delphinapterus leucas) sounds in the wild, Schevill and Lawrence wrote that "occasionally the calls would suggest a crowd of children shouting in the distance". Fish and Mowbary described sound types and reviewed past descriptions of sounds from this vociferous species. At Vancouver Aquarium, Canada, keepers suggested that a white whale about 15 years of age, uttered his name "Lagosi". Other utterances were not perceptible, being described as "garbled human voice, or Russian, or similar to Chinese" by R.L. Eaton in a self-published account in 1979. However, hitherto no acoustic recordings have shown how such sounds emulate speech and deviate from the usual calls of the species. We report here sound recordings and analysis which demonstrate spontaneous mimicry of the human voice, presumably a result of vocal learning, by a white whale. PMID:23098588

  9. Associative and spontaneous appraisal processes independently contribute to anger elicitation in daily life.

    PubMed

    Wilkowski, Benjamin M; Robinson, Michael D

    2010-04-01

    There has been a great deal of debate concerning the antecedents of anger, with appraisal theorists emphasizing the role of hostile interpretations and cognitive neo-associationistic theorists emphasizing the role of more basic associative processes. Recently, theorists have sought to reconcile these views by acknowledging the role of both associative and inferential processes, and the current investigation drew upon recent social-cognitive research to test this compromise. Individual differences in hostile inferences and associations were assessed in an implicit cognitive paradigm, and relevant outcomes were assessed in a daily diary protocol. Implicit hostile inferences predicted both anger and aggression in daily life, and such relationships were mediated by propensities toward hostile interpretations in daily life. Hostile associations also predicted anger in daily life, but this relationship proved to be independent of daily hostile interpretations. Results therefore support a model that acknowledges the role of both associative and appraisal processes in anger elicitation.

  10. Bridging the Mechanical and the Human Mind: Spontaneous Mimicry of a Physically Present Android

    PubMed Central

    Hofree, Galit; Ruvolo, Paul; Bartlett, Marian Stewart; Winkielman, Piotr

    2014-01-01

    The spontaneous mimicry of others' emotional facial expressions constitutes a rudimentary form of empathy and facilitates social understanding. Here, we show that human participants spontaneously match facial expressions of an android physically present in the room with them. This mimicry occurs even though these participants find the android unsettling and are fully aware that it lacks intentionality. Interestingly, a video of that same android elicits weaker mimicry reactions, occurring only in participants who find the android “humanlike.” These findings suggest that spontaneous mimicry depends on the salience of humanlike features highlighted by face-to-face contact, emphasizing the role of presence in human-robot interaction. Further, the findings suggest that mimicry of androids can dissociate from knowledge of artificiality and experienced emotional unease. These findings have implications for theoretical debates about the mechanisms of imitation. They also inform creation of future robots that effectively build rapport and engagement with their human users. PMID:25036365

  11. Bridging the mechanical and the human mind: spontaneous mimicry of a physically present android.

    PubMed

    Hofree, Galit; Ruvolo, Paul; Bartlett, Marian Stewart; Winkielman, Piotr

    2014-01-01

    The spontaneous mimicry of others' emotional facial expressions constitutes a rudimentary form of empathy and facilitates social understanding. Here, we show that human participants spontaneously match facial expressions of an android physically present in the room with them. This mimicry occurs even though these participants find the android unsettling and are fully aware that it lacks intentionality. Interestingly, a video of that same android elicits weaker mimicry reactions, occurring only in participants who find the android "humanlike." These findings suggest that spontaneous mimicry depends on the salience of humanlike features highlighted by face-to-face contact, emphasizing the role of presence in human-robot interaction. Further, the findings suggest that mimicry of androids can dissociate from knowledge of artificiality and experienced emotional unease. These findings have implications for theoretical debates about the mechanisms of imitation. They also inform creation of future robots that effectively build rapport and engagement with their human users.

  12. Honey supplementation in spontaneously hypertensive rats elicits antihypertensive effect via amelioration of renal oxidative stress.

    PubMed

    Erejuwa, Omotayo O; Sulaiman, Siti A; Ab Wahab, Mohd S; Sirajudeen, Kuttulebbai N S; Salleh, Salzihan; Gurtu, Sunil

    2012-01-01

    Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY) rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA) levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione S-transferase (GST) were significantly downregulated while total antioxidant status (TAS) and activities of GST and catalase (CAT) were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR.

  13. Spontaneous slow replication fork progression elicits mitosis alterations in homologous recombination-deficient mammalian cells.

    PubMed

    Wilhelm, Therese; Magdalou, Indiana; Barascu, Aurélia; Técher, Hervé; Debatisse, Michelle; Lopez, Bernard S

    2014-01-14

    Homologous recombination deficient (HR(-)) mammalian cells spontaneously display reduced replication fork (RF) movement and mitotic extra centrosomes. We show here that these cells present a complex mitotic phenotype, including prolonged metaphase arrest, anaphase bridges, and multipolar segregations. We then asked whether the replication and the mitotic phenotypes are interdependent. First, we determined low doses of hydroxyurea that did not affect the cell cycle distribution or activate CHK1 phosphorylation but did slow the replication fork movement of wild-type cells to the same level than in HR(-) cells. Remarkably, these low hydroxyurea doses generated the same mitotic defects (and to the same extent) in wild-type cells as observed in unchallenged HR(-) cells. Reciprocally, supplying nucleotide precursors to HR(-) cells suppressed both their replication deceleration and mitotic extra centrosome phenotypes. Therefore, subtle replication stress that escapes to surveillance pathways and, thus, fails to prevent cells from entering mitosis alters metaphase progression and centrosome number, resulting in multipolar mitosis. Importantly, multipolar mitosis results in global unbalanced chromosome segregation involving the whole genome, even fully replicated chromosomes. These data highlight the cross-talk between chromosome replication and segregation, and the importance of HR at the interface of these two processes for protection against general genome instability.

  14. Auditory Evoked Fields Elicited by Spectral, Temporal, and Spectral–Temporal Changes in Human Cerebral Cortex

    PubMed Central

    Okamoto, Hidehiko; Teismann, Henning; Kakigi, Ryusuke; Pantev, Christo

    2012-01-01

    Natural sounds contain complex spectral components, which are temporally modulated as time-varying signals. Recent studies have suggested that the auditory system encodes spectral and temporal sound information differently. However, it remains unresolved how the human brain processes sounds containing both spectral and temporal changes. In the present study, we investigated human auditory evoked responses elicited by spectral, temporal, and spectral–temporal sound changes by means of magnetoencephalography. The auditory evoked responses elicited by the spectral–temporal change were very similar to those elicited by the spectral change, but those elicited by the temporal change were delayed by 30–50 ms and differed from the others in morphology. The results suggest that human brain responses corresponding to spectral sound changes precede those corresponding to temporal sound changes, even when the spectral and temporal changes occur simultaneously. PMID:22593751

  15. Human Papillomavirus Infection as a Possible Cause of Spontaneous Abortion and Spontaneous Preterm Delivery.

    PubMed

    Ambühl, Lea Maria Margareta; Baandrup, Ulrik; Dybkær, Karen; Blaakær, Jan; Uldbjerg, Niels; Sørensen, Suzette

    2016-01-01

    Based on the current literature, we aimed to provide an overview on Human Papillomavirus prevalence in normal pregnancies and pregnancies with adverse outcome. We conducted a systematic literature search in PubMed and Embase. Data extracted from the articles and used for analysis included HPV prevalence, pregnancy outcome, geographical location, investigated tissue types, and HPV detection methods. The overall HPV prevalence in normal full-term pregnancies was found to be 17.5% (95% CI; 17.3-17.7) for cervix, 8.3% (95% CI; 7.6-9.1) for placental tissue, 5.7% (95% CI; 5.1-6.3) for amniotic fluid, and 10.9% (95% CI; 10.1-11.7) for umbilical cord blood. Summary estimates for HPV prevalence of spontaneous abortions and spontaneous preterm deliveries, in cervix (spontaneous abortions: 24.5%, and preterm deliveries: 47%, resp.) and placenta (spontaneous abortions: 24.9%, and preterm deliveries: 50%, resp.), were identified to be higher compared to normal full-term pregnancies (P < 0.05 and P < 0.0001). Great variation in HPV prevalence was observed between study populations of different geographical locations. This review demonstrates an association between spontaneous abortion, spontaneous preterm delivery, and the presence of HPV in both the cervix and the placenta. However, a reliable conclusion is difficult to draw due to the limited number of studies conducted on material from pregnancies with adverse outcome and the risk of residual confounding. PMID:27110088

  16. Human Papillomavirus Infection as a Possible Cause of Spontaneous Abortion and Spontaneous Preterm Delivery.

    PubMed

    Ambühl, Lea Maria Margareta; Baandrup, Ulrik; Dybkær, Karen; Blaakær, Jan; Uldbjerg, Niels; Sørensen, Suzette

    2016-01-01

    Based on the current literature, we aimed to provide an overview on Human Papillomavirus prevalence in normal pregnancies and pregnancies with adverse outcome. We conducted a systematic literature search in PubMed and Embase. Data extracted from the articles and used for analysis included HPV prevalence, pregnancy outcome, geographical location, investigated tissue types, and HPV detection methods. The overall HPV prevalence in normal full-term pregnancies was found to be 17.5% (95% CI; 17.3-17.7) for cervix, 8.3% (95% CI; 7.6-9.1) for placental tissue, 5.7% (95% CI; 5.1-6.3) for amniotic fluid, and 10.9% (95% CI; 10.1-11.7) for umbilical cord blood. Summary estimates for HPV prevalence of spontaneous abortions and spontaneous preterm deliveries, in cervix (spontaneous abortions: 24.5%, and preterm deliveries: 47%, resp.) and placenta (spontaneous abortions: 24.9%, and preterm deliveries: 50%, resp.), were identified to be higher compared to normal full-term pregnancies (P < 0.05 and P < 0.0001). Great variation in HPV prevalence was observed between study populations of different geographical locations. This review demonstrates an association between spontaneous abortion, spontaneous preterm delivery, and the presence of HPV in both the cervix and the placenta. However, a reliable conclusion is difficult to draw due to the limited number of studies conducted on material from pregnancies with adverse outcome and the risk of residual confounding.

  17. Human Papillomavirus Infection as a Possible Cause of Spontaneous Abortion and Spontaneous Preterm Delivery

    PubMed Central

    Ambühl, Lea Maria Margareta; Baandrup, Ulrik; Dybkær, Karen; Blaakær, Jan; Uldbjerg, Niels; Sørensen, Suzette

    2016-01-01

    Based on the current literature, we aimed to provide an overview on Human Papillomavirus prevalence in normal pregnancies and pregnancies with adverse outcome. We conducted a systematic literature search in PubMed and Embase. Data extracted from the articles and used for analysis included HPV prevalence, pregnancy outcome, geographical location, investigated tissue types, and HPV detection methods. The overall HPV prevalence in normal full-term pregnancies was found to be 17.5% (95% CI; 17.3–17.7) for cervix, 8.3% (95% CI; 7.6–9.1) for placental tissue, 5.7% (95% CI; 5.1–6.3) for amniotic fluid, and 10.9% (95% CI; 10.1–11.7) for umbilical cord blood. Summary estimates for HPV prevalence of spontaneous abortions and spontaneous preterm deliveries, in cervix (spontaneous abortions: 24.5%, and preterm deliveries: 47%, resp.) and placenta (spontaneous abortions: 24.9%, and preterm deliveries: 50%, resp.), were identified to be higher compared to normal full-term pregnancies (P < 0.05 and P < 0.0001). Great variation in HPV prevalence was observed between study populations of different geographical locations. This review demonstrates an association between spontaneous abortion, spontaneous preterm delivery, and the presence of HPV in both the cervix and the placenta. However, a reliable conclusion is difficult to draw due to the limited number of studies conducted on material from pregnancies with adverse outcome and the risk of residual confounding. PMID:27110088

  18. Spontaneous Regeneration of Human Photoreceptor Outer Segments.

    PubMed

    Horton, Jonathan C; Parker, Alicia B; Botelho, James V; Duncan, Jacque L

    2015-01-01

    Photoreceptors are damaged in many common eye diseases, such as macular degeneration, retinal detachment, and retinitis pigmentosa. The development of methods to promote the repair or replacement of affected photoreceptors is a major goal of vision research. In this context, it would be useful to know whether photoreceptors are capable of undergoing some degree of spontaneous regeneration after injury. We report a subject who lost retinal function in a wide zone around the optic disc, giving rise to massive enlargement of the physiological blind spot. Imaging with an adaptive optics scanning laser ophthalmoscope (AOSLO) showed depletion of cone outer segments in the affected retina. A year later visual function had improved, with shrinkage of the enlarged blind spot. AOSLO imaging showed repopulation of cone outer segments, although their density remained below normal. There was a one-to-one match between sites of formerly missing outer segments and new outer segments that had appeared over the course of the year's recovery. This correspondence provided direct morphological evidence that damaged cones are capable, under some circumstances, of generating new outer segments. PMID:26213154

  19. Spontaneous Regeneration of Human Photoreceptor Outer Segments

    PubMed Central

    Horton, Jonathan C.; Parker, Alicia B.; Botelho, James V.; Duncan, Jacque L.

    2015-01-01

    Photoreceptors are damaged in many common eye diseases, such as macular degeneration, retinal detachment, and retinitis pigmentosa. The development of methods to promote the repair or replacement of affected photoreceptors is a major goal of vision research. In this context, it would be useful to know whether photoreceptors are capable of undergoing some degree of spontaneous regeneration after injury. We report a subject who lost retinal function in a wide zone around the optic disc, giving rise to massive enlargement of the physiological blind spot. Imaging with an adaptive optics scanning laser ophthalmoscope (AOSLO) showed depletion of cone outer segments in the affected retina. A year later visual function had improved, with shrinkage of the enlarged blind spot. AOSLO imaging showed repopulation of cone outer segments, although their density remained below normal. There was a one-to-one match between sites of formerly missing outer segments and new outer segments that had appeared over the course of the year’s recovery. This correspondence provided direct morphological evidence that damaged cones are capable, under some circumstances, of generating new outer segments. PMID:26213154

  20. Canine tumors: a spontaneous animal model of human carcinogenesis.

    PubMed

    Pinho, Salomé S; Carvalho, Sandra; Cabral, Joana; Reis, Celso A; Gärtner, Fátima

    2012-03-01

    The enormous biologic complexity of human cancer has stimulated the development of more appropriate experimental models that could resemble in a natural and spontaneous manner the physiopathologic aspects of cancer biology. Companion animals have many desired characteristics that fill the gap between in vitro and in vivo studies, and these characteristics have proven to be important in understanding many complex molecular aspects of human cancer. Spontaneous tumors in dogs share a wide variety of epidemiologic, biologic, and clinical features with human cancer, which makes this animal model both attractive and underused in oncology research. In this review, we summarize the importance of naturally occurring canine tumors as valuable tools for studying numerous aspects of human cancer as well as the potential use of this animal model for the development of new cancer treatments. We address specifically the use of canine mammary tumors as an increasingly powerful model to study human breast cancer. PMID:22340765

  1. Music-Elicited Emotion Identification Using Optical Flow Analysis of Human Face

    NASA Astrophysics Data System (ADS)

    Kniaz, V. V.; Smirnova, Z. N.

    2015-05-01

    Human emotion identification from image sequences is highly demanded nowadays. The range of possible applications can vary from an automatic smile shutter function of consumer grade digital cameras to Biofied Building technologies, which enables communication between building space and residents. The highly perceptual nature of human emotions leads to the complexity of their classification and identification. The main question arises from the subjective quality of emotional classification of events that elicit human emotions. A variety of methods for formal classification of emotions were developed in musical psychology. This work is focused on identification of human emotions evoked by musical pieces using human face tracking and optical flow analysis. Facial feature tracking algorithm used for facial feature speed and position estimation is presented. Facial features were extracted from each image sequence using human face tracking with local binary patterns (LBP) features. Accurate relative speeds of facial features were estimated using optical flow analysis. Obtained relative positions and speeds were used as the output facial emotion vector. The algorithm was tested using original software and recorded image sequences. The proposed technique proves to give a robust identification of human emotions elicited by musical pieces. The estimated models could be used for human emotion identification from image sequences in such fields as emotion based musical background or mood dependent radio.

  2. CD4-Mimetic Small Molecules Sensitize Human Immunodeficiency Virus to Vaccine-Elicited Antibodies

    PubMed Central

    Madani, Navid; Princiotto, Amy M.; Schön, Arne; LaLonde, Judith; Feng, Yu; Freire, Ernesto; Park, Jongwoo; Courter, Joel R.; Jones, David M.; Robinson, James; Liao, Hua-Xin; Moody, M. Anthony; Permar, Sallie; Haynes, Barton; Smith, Amos B.; Wyatt, Richard

    2014-01-01

    ABSTRACT Approaches to prevent human immunodeficiency virus (HIV-1) transmission are urgently needed. Difficulties in eliciting antibodies that bind conserved epitopes exposed on the unliganded conformation of the HIV-1 envelope glycoprotein (Env) trimer represent barriers to vaccine development. During HIV-1 entry, binding of the gp120 Env to the initial receptor, CD4, triggers conformational changes in Env that result in the formation and exposure of the highly conserved gp120 site for interaction with the coreceptors, CCR5 and CXCR4. The DMJ compounds (+)-DMJ-I-228 and (+)-DMJ-II-121 bind gp120 within the conserved Phe 43 cavity near the CD4-binding site, block CD4 binding, and inhibit HIV-1 infection. Here we show that the DMJ compounds sensitize primary HIV-1, including transmitted/founder viruses, to neutralization by monoclonal antibodies directed against CD4-induced (CD4i) epitopes and the V3 region, two gp120 elements involved in coreceptor binding. Importantly, the DMJ compounds rendered primary HIV-1 sensitive to neutralization by antisera elicited by immunization of rabbits with HIV-1 gp120 cores engineered to assume the CD4-bound state. Thus, small molecules like the DMJ compounds may be useful as microbicides to inhibit HIV-1 infection directly and to sensitize primary HIV-1 to neutralization by readily elicited antibodies. IMPORTANCE Preventing HIV-1 transmission is a priority for global health. Eliciting antibodies that can neutralize many different strains of HIV-1 is difficult, creating problems for the development of a vaccine. We found that certain small-molecule compounds can sensitize HIV-1 to particular antibodies. These antibodies can be elicited in rabbits. These results suggest an approach to prevent HIV-1 sexual transmission in which a virus-sensitizing microbicide is combined with a vaccine. PMID:24696475

  3. Human Neoplasms Elicit Multiple Specific Immune Responses in the Autologous Host

    NASA Astrophysics Data System (ADS)

    Sahin, Ugur; Tureci, Ozlem; Schmitt, Holger; Cochlovius, Bjorn; Johannes, Thomas; Schmits, Rudolf; Stenner, Frank; Luo, Guorong; Schobert, Ingrid; Pfreundschuh, Michael

    1995-12-01

    Expression of cDNA libraries from human melanoma, renal cancer, astrocytoma, and Hodgkin disease in Escherichia coli and screening for clones reactive with high-titer IgG antibodies in autologous patient serum lead to the discovery of at least four antigens with a restricted expression pattern in each tumor. Besides antigens known to elicit T-cell responses, such as MAGE-1 and tyrosinase, numerous additional antigens that were overexpressed or specifically expressed in tumors of the same type were identified. Sequence analyses suggest that many of these molecules, besides being the target of a specific immune response, might be of relevance for tumor growth. Antibodies to a given antigen were usually confined to patients with the same tumor type. The unexpected frequency of human tumor antigens, which can be readily defined at the molecular level by the serological analysis of autologous tumor cDNA expression cloning, indicates that human neoplasms elicit multiple specific immune responses in the autologous host and provides diagnostic and therapeutic approaches to human cancer.

  4. Accumulated Bending Energy Elicits Neutral Sphingomyelinase Activity in Human Red Blood Cells

    PubMed Central

    López, David J.; Egido-Gabas, Meritxell; López-Montero, Iván; Busto, Jon V.; Casas, Josefina; Garnier, Marie; Monroy, Francisco; Larijani, Banafshé; Goñi, Félix M.; Alonso, Alicia

    2012-01-01

    We propose that accumulated membrane bending energy elicits a neutral sphingomyelinase (SMase) activity in human erythrocytes. Membrane bending was achieved by osmotic or chemical processes, and SMase activity was assessed by quantitative thin-layer chromatography, high-performance liquid chromatography, and electrospray ionization-mass spectrometry. The activity induced by hypotonic stress in erythrocyte membranes had the pH dependence, ion dependence, and inhibitor sensitivity of mammalian neutral SMases. The activity caused a decrease in SM contents, with a minimum at 6 min after onset of the hypotonic conditions, and then the SM contents were recovered. We also elicited SMase activity by adding lysophosphatidylcholine externally or by generating it with phospholipase A2. The same effect was observed upon addition of chlorpromazine or sodium deoxycholate at concentrations below the critical micellar concentration, and even under hypertonic conditions. A unifying factor of the various agents that elicit this SMase activity is the accumulated membrane bending energy. Both hypo-and hypertonic conditions impose an increased curvature, whereas the addition of surfactants or phospholipase A2 activation increases the outer monolayer area, thus leading to an increased bending energy. The fact that this latent SMase activity is tightly coupled to the membrane bending properties suggests that it may be related to the general phenomenon of stress-induced ceramide synthesis and apoptosis. PMID:22824271

  5. Chimpanzee drumming: a spontaneous performance with characteristics of human musical drumming

    PubMed Central

    Dufour, Valérie; Poulin, Nicolas; Charlotte Curé; Sterck, Elisabeth H. M.

    2015-01-01

    Despite the quintessential role that music plays in human societies by enabling us to release and share emotions with others, traces of its evolutionary origins in other species remain scarce. Drumming like humans whilst producing music is practically unheard of in our most closely related species, the great apes. Although beating on tree roots and body parts does occur in these species, it has, musically speaking, little in common with human drumming. Researchers suggest that for manual beating in great apes to be compared to human drumming, it should at least be structurally even, a necessary quality to elicit entrainment (beat induction in others). Here we report an episode of spontaneous drumming by a captive chimpanzee that approaches the structural and contextual characteristics usually found in musical drumming. This drumming differs from most beating episodes reported in this species by its unusual duration, the lack of any obvious context, and rhythmical properties that include long-lasting and dynamically changing rhythms, but also evenness and leisureliness. This performance is probably the first evidence that our capacity to drum is shared with our closest relatives. PMID:26080900

  6. Chimpanzee drumming: a spontaneous performance with characteristics of human musical drumming.

    PubMed

    Dufour, Valérie; Poulin, Nicolas; Charlotte Curé; Sterck, Elisabeth H M

    2015-01-01

    Despite the quintessential role that music plays in human societies by enabling us to release and share emotions with others, traces of its evolutionary origins in other species remain scarce. Drumming like humans whilst producing music is practically unheard of in our most closely related species, the great apes. Although beating on tree roots and body parts does occur in these species, it has, musically speaking, little in common with human drumming. Researchers suggest that for manual beating in great apes to be compared to human drumming, it should at least be structurally even, a necessary quality to elicit entrainment (beat induction in others). Here we report an episode of spontaneous drumming by a captive chimpanzee that approaches the structural and contextual characteristics usually found in musical drumming. This drumming differs from most beating episodes reported in this species by its unusual duration, the lack of any obvious context, and rhythmical properties that include long-lasting and dynamically changing rhythms, but also evenness and leisureliness. This performance is probably the first evidence that our capacity to drum is shared with our closest relatives. PMID:26080900

  7. Decoding Spontaneous Emotional States in the Human Brain

    PubMed Central

    Kragel, Philip A.; Knodt, Annchen R.; Hariri, Ahmad R.; LaBar, Kevin S.

    2016-01-01

    Pattern classification of human brain activity provides unique insight into the neural underpinnings of diverse mental states. These multivariate tools have recently been used within the field of affective neuroscience to classify distributed patterns of brain activation evoked during emotion induction procedures. Here we assess whether neural models developed to discriminate among distinct emotion categories exhibit predictive validity in the absence of exteroceptive emotional stimulation. In two experiments, we show that spontaneous fluctuations in human resting-state brain activity can be decoded into categories of experience delineating unique emotional states that exhibit spatiotemporal coherence, covary with individual differences in mood and personality traits, and predict on-line, self-reported feelings. These findings validate objective, brain-based models of emotion and show how emotional states dynamically emerge from the activity of separable neural systems. PMID:27627738

  8. Decoding Spontaneous Emotional States in the Human Brain.

    PubMed

    Kragel, Philip A; Knodt, Annchen R; Hariri, Ahmad R; LaBar, Kevin S

    2016-09-01

    Pattern classification of human brain activity provides unique insight into the neural underpinnings of diverse mental states. These multivariate tools have recently been used within the field of affective neuroscience to classify distributed patterns of brain activation evoked during emotion induction procedures. Here we assess whether neural models developed to discriminate among distinct emotion categories exhibit predictive validity in the absence of exteroceptive emotional stimulation. In two experiments, we show that spontaneous fluctuations in human resting-state brain activity can be decoded into categories of experience delineating unique emotional states that exhibit spatiotemporal coherence, covary with individual differences in mood and personality traits, and predict on-line, self-reported feelings. These findings validate objective, brain-based models of emotion and show how emotional states dynamically emerge from the activity of separable neural systems. PMID:27627738

  9. Arrhythmias, elicited by catecholamines and serotonin, vanish in human chronic atrial fibrillation.

    PubMed

    Christ, Torsten; Rozmaritsa, Nadiia; Engel, Andreas; Berk, Emanuel; Knaut, Michael; Metzner, Katharina; Canteras, Manuel; Ravens, Ursula; Kaumann, Alberto

    2014-07-29

    Atrial fibrillation (AF) is the most common heart rhythm disorder. Transient postoperative AF can be elicited by high sympathetic nervous system activity. Catecholamines and serotonin cause arrhythmias in atrial trabeculae from patients with sinus rhythm (SR), but whether these arrhythmias occur in patients with chronic AF is unknown. We compared the incidence of arrhythmic contractions caused by norepinephrine, epinephrine, serotonin, and forskolin in atrial trabeculae from patients with SR and patients with AF. In the patients with AF, arrhythmias were markedly reduced for the agonists and abolished for forskolin, whereas maximum inotropic responses were markedly blunted only for serotonin. Serotonin and forskolin produced spontaneous diastolic Ca(2+) releases in atrial myocytes from the patients with SR that were abolished or reduced in myocytes from the patients with AF. For matching L-type Ca(2+)-current (ICa,L) responses, serotonin required and produced ∼ 100-fold less cAMP/PKA at the Ca(2+) channel domain compared with the catecholamines and forskolin. Norepinephrine-evoked ICa,L responses were decreased by inhibition of Ca(2+)/calmodulin-dependent kinase II (CaMKII) in myocytes from patients with SR, but not in those from patients with AF. Agonist-evoked phosphorylation by CaMKII at phospholamban (Thr-17), but not of ryanodine2 (Ser-2814), was reduced in trabeculae from patients with AF. The decreased CaMKII activity may contribute to the blunting of agonist-evoked arrhythmias in the atrial myocardium of patients with AF. PMID:25024212

  10. Reward feedback stimuli elicit high-beta EEG oscillations in human dorsolateral prefrontal cortex

    PubMed Central

    Hosseini, Azadeh Haji; Holroyd, Clay B.

    2015-01-01

    Reward-related feedback stimuli have been observed to elicit a burst of power in the beta frequency range over frontal areas of the human scalp. Recent discussions have suggested possible neural sources for this activity but there is a paucity of empirical evidence on the question. Here we recorded EEG from participants while they navigated a virtual T-maze to find monetary rewards. Consistent with previous studies, we found that the reward feedback stimuli elicited an increase in beta power (20–30 Hz) over a right-frontal area of the scalp. Source analysis indicated that this signal was produced in the right dorsolateral prefrontal cortex (DLPFC). These findings align with previous observations of reward-related beta oscillations in the DLPFC in non-human primates. We speculate that increased power in the beta frequency range following reward receipt reflects the activation of task-related neural assemblies that encode the stimulus-response mapping in working memory. PMID:26278335

  11. Intraneural stimulation elicits discrimination of textural features by artificial fingertip in intact and amputee humans.

    PubMed

    Oddo, Calogero Maria; Raspopovic, Stanisa; Artoni, Fiorenzo; Mazzoni, Alberto; Spigler, Giacomo; Petrini, Francesco; Giambattistelli, Federica; Vecchio, Fabrizio; Miraglia, Francesca; Zollo, Loredana; Di Pino, Giovanni; Camboni, Domenico; Carrozza, Maria Chiara; Guglielmelli, Eugenio; Rossini, Paolo Maria; Faraguna, Ugo; Micera, Silvestro

    2016-01-01

    Restoration of touch after hand amputation is a desirable feature of ideal prostheses. Here, we show that texture discrimination can be artificially provided in human subjects by implementing a neuromorphic real-time mechano-neuro-transduction (MNT), which emulates to some extent the firing dynamics of SA1 cutaneous afferents. The MNT process was used to modulate the temporal pattern of electrical spikes delivered to the human median nerve via percutaneous microstimulation in four intact subjects and via implanted intrafascicular stimulation in one transradial amputee. Both approaches allowed the subjects to reliably discriminate spatial coarseness of surfaces as confirmed also by a hybrid neural model of the median nerve. Moreover, MNT-evoked EEG activity showed physiologically plausible responses that were superimposable in time and topography to the ones elicited by a natural mechanical tactile stimulation. These findings can open up novel opportunities for sensory restoration in the next generation of neuro-prosthetic hands. PMID:26952132

  12. Survey of the human acetylator polymorphism in spontaneous disorders.

    PubMed Central

    Evans, D A

    1984-01-01

    There is ample evidence that the human acetylator phenotypes are associated with drug induced phenomena. It is principally the slow acetylators who exhibit toxic adverse effects because of their relative inability to detoxify the original drug compounds. In rare instances, however, it is the rapid acetylators who are at a disadvantage. In the matter of association of spontaneous disease with either acetylator phenotype, there are two groups of disorders to consider. First, disorders in which carcinogenic amines are known to be an aetiological factor. This is because these amines are substrates for the polymorphic N-acetyltransferase activity and hence there is a possible rational basis for searching for an association. Secondly, other disorders where searches for associations are based more on hunches. In the first group there is a definite statistical association between cancer of the bladder and the slow acetylator phenotype. In prevalence studies the slow phenotype is 39% more associated with bladder cancer than is the rapid phenotype. On the basis of the evidence now available it is not possible to say whether this association is because slow acetylators develop the disease more frequently or whether they survive longer. In the second group the relevant studies show (1) a greatly increased prevalence of slow acetylators in Gilbert's disease; (2) a confirmed association between the rapid acetylator phenotype and diabetes; (3) a possible association between the rapid acetylator phenotype and breast cancer; (4) a possible association between the slow acetylator phenotype and leprosy in Chinese patients; (5) an earlier age of onset of thyrotoxicosis (Graves' disease) in slow acetylators than in rapid acetylators; (6) no evidence of an association between either phenotype and spontaneous systemic lupus erythematosus. PMID:6387123

  13. Rod Electroretinograms Elicited by Silent Substitution Stimuli from the Light-Adapted Human Eye

    PubMed Central

    Maguire, John; Parry, Neil R. A.; Kremers, Jan; Kommanapalli, Deepika; Murray, Ian J.; McKeefry, Declan J.

    2016-01-01

    Purpose To demonstrate that silent substitution stimuli can be used to generate electroretinograms (ERGs) that effectively isolate rod photoreceptor function in humans without the need for dark adaptation, and that this approach constitutes a viable alternative to current clinical standard testing protocols. Methods Rod-isolating and non-isolating sinusoidal flicker stimuli were generated on a 4 primary light-emitting diode (LED) Ganzfeld stimulator to elicit ERGs from participants with normal and compromised rod function who had not undergone dark-adaptation. Responses were subjected to Fourier analysis, and the amplitude and phase of the fundamental were used to examine temporal frequency and retinal illuminance response characteristics. Results Electroretinograms elicited by rod-isolating silent substitution stimuli exhibit low-pass temporal frequency response characteristics with an upper response limit of 30 Hz. Responses are optimal between 5 and 8 Hz and between 10 and 100 photopic trolands (Td). There is a significant correlation between the response amplitudes obtained with the silent substitution method and current standard clinical protocols. Analysis of signal-to-noise ratios reveals significant differences between subjects with normal and compromised rod function. Conclusions Silent substitution provides an effective method for the isolation of human rod photoreceptor function in subjects with normal as well as compromised rod function when stimuli are used within appropriate parameter ranges. Translational Relevance This method of generating rod-mediated ERGs can be achieved without time-consuming periods of dark adaptation, provides improved isolation of rod- from cone-based activity, and will lead to the development of faster clinical electrophysiologic testing protocols with improved selectivity.

  14. Rod Electroretinograms Elicited by Silent Substitution Stimuli from the Light-Adapted Human Eye

    PubMed Central

    Maguire, John; Parry, Neil R. A.; Kremers, Jan; Kommanapalli, Deepika; Murray, Ian J.; McKeefry, Declan J.

    2016-01-01

    Purpose To demonstrate that silent substitution stimuli can be used to generate electroretinograms (ERGs) that effectively isolate rod photoreceptor function in humans without the need for dark adaptation, and that this approach constitutes a viable alternative to current clinical standard testing protocols. Methods Rod-isolating and non-isolating sinusoidal flicker stimuli were generated on a 4 primary light-emitting diode (LED) Ganzfeld stimulator to elicit ERGs from participants with normal and compromised rod function who had not undergone dark-adaptation. Responses were subjected to Fourier analysis, and the amplitude and phase of the fundamental were used to examine temporal frequency and retinal illuminance response characteristics. Results Electroretinograms elicited by rod-isolating silent substitution stimuli exhibit low-pass temporal frequency response characteristics with an upper response limit of 30 Hz. Responses are optimal between 5 and 8 Hz and between 10 and 100 photopic trolands (Td). There is a significant correlation between the response amplitudes obtained with the silent substitution method and current standard clinical protocols. Analysis of signal-to-noise ratios reveals significant differences between subjects with normal and compromised rod function. Conclusions Silent substitution provides an effective method for the isolation of human rod photoreceptor function in subjects with normal as well as compromised rod function when stimuli are used within appropriate parameter ranges. Translational Relevance This method of generating rod-mediated ERGs can be achieved without time-consuming periods of dark adaptation, provides improved isolation of rod- from cone-based activity, and will lead to the development of faster clinical electrophysiologic testing protocols with improved selectivity. PMID:27617180

  15. Reducing social stress elicits emotional contagion of pain in mouse and human strangers.

    PubMed

    Martin, Loren J; Hathaway, Georgia; Isbester, Kelsey; Mirali, Sara; Acland, Erinn L; Niederstrasser, Nils; Slepian, Peter M; Trost, Zina; Bartz, Jennifer A; Sapolsky, Robert M; Sternberg, Wendy F; Levitin, Daniel J; Mogil, Jeffrey S

    2015-02-01

    Empathy for another's physical pain has been demonstrated in humans [1] and mice [2]; in both species, empathy is stronger between familiars. Stress levels in stranger dyads are higher than in cagemate dyads or isolated mice [2, 3], suggesting that stress might be responsible for the absence of empathy for the pain of strangers. We show here that blockade of glucocorticoid synthesis or receptors for adrenal stress hormones elicits the expression of emotional contagion (a form of empathy) in strangers of both species. Mice and undergraduates were tested for sensitivity to noxious stimulation alone and/or together (dyads). In familiar, but not stranger, pairs, dyadic testing was associated with increased pain behaviors or ratings compared to isolated testing. Pharmacological blockade of glucocorticoid synthesis or glucocorticoid and mineralocorticoid receptors enabled the expression of emotional contagion of pain in mouse and human stranger dyads, as did a shared gaming experience (the video game Rock Band) in human strangers. Our results demonstrate that emotional contagion is prevented, in an evolutionarily conserved manner, by the stress of a social interaction with an unfamiliar conspecific and can be evoked by blocking the endocrine stress response.

  16. Periodic modulation of repetitively elicited monosynaptic reflexes of the human lumbosacral spinal cord

    PubMed Central

    Danner, Simon M.; Freundl, Brigitta; Binder, Heinrich; Mayr, Winfried; Rattay, Frank; Minassian, Karen

    2015-01-01

    In individuals with motor-complete spinal cord injury, epidural stimulation of the lumbosacral spinal cord at 2 Hz evokes unmodulated reflexes in the lower limbs, while stimulation at 22–60 Hz can generate rhythmic burstlike activity. Here we elaborated on an output pattern emerging at transitional stimulation frequencies with consecutively elicited reflexes alternating between large and small. We analyzed responses concomitantly elicited in thigh and leg muscle groups bilaterally by epidural stimulation in eight motor-complete spinal cord-injured individuals. Periodic amplitude modulation of at least 20 successive responses occurred in 31.4% of all available data sets with stimulation frequency set at 5–26 Hz, with highest prevalence at 16 Hz. It could be evoked in a single muscle group only but was more strongly expressed and consistent when occurring in pairs of antagonists or in the same muscle group bilaterally. Latencies and waveforms of the modulated reflexes corresponded to those of the unmodulated, monosynaptic responses to 2-Hz stimulation. We suggest that the cyclical changes of reflex excitability resulted from the interaction of facilitatory and inhibitory mechanisms emerging after specific delays and with distinct durations, including postactivation depression, recurrent inhibition and facilitation, as well as reafferent feedback activation. The emergence of large responses within the patterns at a rate of 5.5/s or 8/s may further suggest the entrainment of spinal mechanisms as involved in clonus. The study demonstrates that the human lumbosacral spinal cord can organize a simple form of rhythmicity through the repetitive activation of spinal reflex circuits. PMID:25904708

  17. Periodic modulation of repetitively elicited monosynaptic reflexes of the human lumbosacral spinal cord.

    PubMed

    Hofstoetter, Ursula S; Danner, Simon M; Freundl, Brigitta; Binder, Heinrich; Mayr, Winfried; Rattay, Frank; Minassian, Karen

    2015-07-01

    In individuals with motor-complete spinal cord injury, epidural stimulation of the lumbosacral spinal cord at 2 Hz evokes unmodulated reflexes in the lower limbs, while stimulation at 22-60 Hz can generate rhythmic burstlike activity. Here we elaborated on an output pattern emerging at transitional stimulation frequencies with consecutively elicited reflexes alternating between large and small. We analyzed responses concomitantly elicited in thigh and leg muscle groups bilaterally by epidural stimulation in eight motor-complete spinal cord-injured individuals. Periodic amplitude modulation of at least 20 successive responses occurred in 31.4% of all available data sets with stimulation frequency set at 5-26 Hz, with highest prevalence at 16 Hz. It could be evoked in a single muscle group only but was more strongly expressed and consistent when occurring in pairs of antagonists or in the same muscle group bilaterally. Latencies and waveforms of the modulated reflexes corresponded to those of the unmodulated, monosynaptic responses to 2-Hz stimulation. We suggest that the cyclical changes of reflex excitability resulted from the interaction of facilitatory and inhibitory mechanisms emerging after specific delays and with distinct durations, including postactivation depression, recurrent inhibition and facilitation, as well as reafferent feedback activation. The emergence of large responses within the patterns at a rate of 5.5/s or 8/s may further suggest the entrainment of spinal mechanisms as involved in clonus. The study demonstrates that the human lumbosacral spinal cord can organize a simple form of rhythmicity through the repetitive activation of spinal reflex circuits. PMID:25904708

  18. Intraneural stimulation elicits discrimination of textural features by artificial fingertip in intact and amputee humans

    PubMed Central

    Oddo, Calogero Maria; Raspopovic, Stanisa; Artoni, Fiorenzo; Mazzoni, Alberto; Spigler, Giacomo; Petrini, Francesco; Giambattistelli, Federica; Vecchio, Fabrizio; Miraglia, Francesca; Zollo, Loredana; Di Pino, Giovanni; Camboni, Domenico; Carrozza, Maria Chiara; Guglielmelli, Eugenio; Rossini, Paolo Maria; Faraguna, Ugo; Micera, Silvestro

    2016-01-01

    Restoration of touch after hand amputation is a desirable feature of ideal prostheses. Here, we show that texture discrimination can be artificially provided in human subjects by implementing a neuromorphic real-time mechano-neuro-transduction (MNT), which emulates to some extent the firing dynamics of SA1 cutaneous afferents. The MNT process was used to modulate the temporal pattern of electrical spikes delivered to the human median nerve via percutaneous microstimulation in four intact subjects and via implanted intrafascicular stimulation in one transradial amputee. Both approaches allowed the subjects to reliably discriminate spatial coarseness of surfaces as confirmed also by a hybrid neural model of the median nerve. Moreover, MNT-evoked EEG activity showed physiologically plausible responses that were superimposable in time and topography to the ones elicited by a natural mechanical tactile stimulation. These findings can open up novel opportunities for sensory restoration in the next generation of neuro-prosthetic hands. DOI: http://dx.doi.org/10.7554/eLife.09148.001 PMID:26952132

  19. Stimulus-Elicited Connectivity Influences Resting-State Connectivity Years Later in Human Development: A Prospective Study

    PubMed Central

    Gee, Dylan Grace; Goff, Bonnie; Flannery, Jessica; Telzer, Eva; Humphreys, Kathryn Leigh; Lumian, Daniel Stephen; Fareri, Dominic Stephen; Caldera, Christina; Tottenham, Nim

    2016-01-01

    Although the functional architecture of the brain is indexed by resting-state connectivity networks, little is currently known about the mechanisms through which these networks assemble into stable mature patterns. The current study posits and tests the long-term phasic molding hypothesis that resting-state networks are gradually shaped by recurring stimulus-elicited connectivity across development by examining how both stimulus-elicited and resting-state functional connections of the human brain emerge over development at the systems level. Using a sequential design following 4- to 18-year-olds over a 2 year period, we examined the predictive associations between stimulus-elicited and resting-state connectivity in amygdala-cortical circuitry as an exemplar case (given this network's protracted development across these ages). Age-related changes in amygdala functional connectivity converged on the same regions of medial prefrontal cortex (mPFC) and inferior frontal gyrus when elicited by emotional stimuli and when measured at rest. Consistent with the long-term phasic molding hypothesis, prospective analyses for both connections showed that the magnitude of an individual's stimulus-elicited connectivity unidirectionally predicted resting-state functional connectivity 2 years later. For the amygdala-mPFC connection, only stimulus-elicited connectivity during childhood and the transition to adolescence shaped future resting-state connectivity, consistent with a sensitive period ending with adolescence for the amygdala-mPFC circuit. Together, these findings suggest that resting-state functional architecture may arise from phasic patterns of functional connectivity elicited by environmental stimuli over the course of development on the order of years. SIGNIFICANCE STATEMENT A fundamental issue in understanding the ontogeny of brain function is how resting-state (intrinsic) functional networks emerge and relate to stimulus-elicited functional connectivity. Here, we

  20. Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates.

    PubMed

    Wang, Qidi; Zhang, Lianfeng; Kuwahara, Kazuhiko; Li, Li; Liu, Zijie; Li, Taisheng; Zhu, Hua; Liu, Jiangning; Xu, Yanfeng; Xie, Jing; Morioka, Hiroshi; Sakaguchi, Nobuo; Qin, Chuan; Liu, Gang

    2016-05-13

    Severe acute respiratory syndrome (SARS) is caused by a coronavirus (SARS-CoV) and has the potential to threaten global public health and socioeconomic stability. Evidence of antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro and in non-human primates clouds the prospects for a safe vaccine. Using antibodies from SARS patients, we identified and characterized SARS-CoV B-cell peptide epitopes with disparate functions. In rhesus macaques, the spike glycoprotein peptides S471-503, S604-625, and S1164-1191 elicited antibodies that efficiently prevented infection in non-human primates. In contrast, peptide S597-603 induced antibodies that enhanced infection both in vitro and in non-human primates by using an epitope sequence-dependent (ESD) mechanism. This peptide exhibited a high level of serological reactivity (64%), which resulted from the additive responses of two tandem epitopes (S597-603 and S604-625) and a long-term human B-cell memory response with antisera from convalescent SARS patients. Thus, peptide-based vaccines against SARS-CoV could be engineered to avoid ADE via elimination of the S597-603 epitope. We provide herein an alternative strategy to prepare a safe and effective vaccine for ADE of viral infection by identifying and eliminating epitope sequence-dependent enhancement of viral infection. PMID:27627203

  1. Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates.

    PubMed

    Wang, Qidi; Zhang, Lianfeng; Kuwahara, Kazuhiko; Li, Li; Liu, Zijie; Li, Taisheng; Zhu, Hua; Liu, Jiangning; Xu, Yanfeng; Xie, Jing; Morioka, Hiroshi; Sakaguchi, Nobuo; Qin, Chuan; Liu, Gang

    2016-05-13

    Severe acute respiratory syndrome (SARS) is caused by a coronavirus (SARS-CoV) and has the potential to threaten global public health and socioeconomic stability. Evidence of antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro and in non-human primates clouds the prospects for a safe vaccine. Using antibodies from SARS patients, we identified and characterized SARS-CoV B-cell peptide epitopes with disparate functions. In rhesus macaques, the spike glycoprotein peptides S471-503, S604-625, and S1164-1191 elicited antibodies that efficiently prevented infection in non-human primates. In contrast, peptide S597-603 induced antibodies that enhanced infection both in vitro and in non-human primates by using an epitope sequence-dependent (ESD) mechanism. This peptide exhibited a high level of serological reactivity (64%), which resulted from the additive responses of two tandem epitopes (S597-603 and S604-625) and a long-term human B-cell memory response with antisera from convalescent SARS patients. Thus, peptide-based vaccines against SARS-CoV could be engineered to avoid ADE via elimination of the S597-603 epitope. We provide herein an alternative strategy to prepare a safe and effective vaccine for ADE of viral infection by identifying and eliminating epitope sequence-dependent enhancement of viral infection.

  2. Effect of muscle metaboreflex activation on spontaneous cardiac baroreflex sensitivity during exercise in humans.

    PubMed

    Hartwich, Doreen; Dear, William E; Waterfall, Jessica L; Fisher, James P

    2011-12-15

    We sought to determine whether the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) is a potential mechanism for the decrease in spontaneous cardiac baroreflex sensitivity (cBRS) during exercise in humans. In protocol 1, 15 male subjects (22 ± 1 years) performed steady-state leg cycling at low (26 ± 4 W) and moderate workloads (105 ± 7 W), under free-flow conditions and with partial flow restriction (bilateral thigh cuff inflation at 100 mmHg) to evoke muscle metaboreflex activation during exercise. In protocol 2, rhythmic handgrip exercise at 35% maximum voluntary contraction was performed with progressive upper arm cuff inflation (0, 80, 100 and 120 mmHg) to elicit graded metaboreflex activation. Both protocols were followed by post-exercise ischaemia (PEI) to isolate the muscle metaboreflex. Leg cycling-induced increases in HR and mean BP were augmented by partial flow restriction (P < 0.05 vs. free flow), while HR and mean BP both remained elevated during PEI (P < 0.05 vs. rest). Leg cycling evoked an intensity-dependent decrease in cBRS (16 ± 2, 7 ± 1 and 2 ± 0.2 ms mmHg(-1) at rest, low and moderate workloads, respectively; P < 0.05), which was further reduced with partial flow restriction (by -2.6 ± 0.8 and -0.4 ± 0.1 ms mmHg(-1) at low and moderate workloads). cBRS remained suppressed during PEI following leg cycling with partial flow restriction (4 ± 1 ms mmHg(-1); P < 0.05 vs. rest). cBRS was unchanged during handgrip under free-flow conditions, handgrip with partial flow restriction and PEI following handgrip (P > 0.05 vs. rest). These data indicate that the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) decreases cardiac baroreflex responsiveness during leg cycling exercise in humans.

  3. Skin-surface cooling elicits peripheral and visceral vasoconstriction in humans.

    PubMed

    Wilson, Thad E; Sauder, Charity L; Kearney, Matthew L; Kuipers, Nathan T; Leuenberger, Urs A; Monahan, Kevin D; Ray, Chester A

    2007-10-01

    Skin-surface cooling elicits a pronounced systemic pressor response, which has previously been reported to be associated with peripheral vasoconstriction and may not fully account for the decrease in systemic vascular conductance. To test the hypothesis that whole body skin-surface cooling would also induce renal and splanchnic vasoconstriction, 14 supine subjects performed 26 skin-surface cooling trials (15-18 degrees C water perfused through a tube-lined suit for 20 min). Oral and mean skin temperature, heart rate, stroke volume (Doppler ultrasound), mean arterial blood pressure (MAP), cutaneous blood velocity (laser-Doppler), and mean blood velocity of the brachial, celiac, renal, and superior mesenteric arteries (Doppler ultrasound) were measured during normothermia and skin-surface cooling. Cardiac output (heart rate x stroke volume) and indexes of vascular conductance (flux or blood velocity/MAP) were calculated. Skin-surface cooling increased MAP (n = 26; 78 +/- 5 to 88 +/- 5 mmHg; mean +/- SD) and decreased mean skin temperature (n = 26; 33.7 +/- 0.7 to 27.5 +/- 1.2 degrees C) and cutaneous (n = 12; 0.93 +/- 0.68 to 0.36 +/- 0.20 flux/mmHg), brachial (n = 10; 32 +/- 15 to 20 +/- 12), celiac (n = 8; 85 +/- 22 to 73 +/- 22 cm.s(-1).mmHg(-1)), superior mesenteric (n = 8; 55 +/- 16 to 48 +/- 10 cm.s(-1).mmHg(-1)), and renal (n = 8; 74 +/- 26 to 64 +/- 20 cm.s(-1).mmHg(-1); all P < 0.05) vascular conductance, without altering oral temperature, cardiac output, heart rate, or stroke volume. These data identify decreases in vascular conductance of skin and of brachial, celiac, superior mesenteric, and renal arteries. Thus it appears that vasoconstriction in both peripheral and visceral arteries contributes importantly to the pressor response produced during skin-surface cooling in humans.

  4. Functional Imaging of Human Vestibular Cortex Activity Elicited by Skull Tap and Auditory Tone Burst

    NASA Technical Reports Server (NTRS)

    Noohi, Fatemeh; Kinnaird, Catherine; Wood, Scott; Bloomberg, Jacob; Mulavara, Ajitkumar; Seidler, Rachael

    2014-01-01

    The aim of the current study was to characterize the brain activation in response to two modes of vestibular stimulation: skull tap and auditory tone burst. The auditory tone burst has been used in previous studies to elicit saccular Vestibular Evoked Myogenic Potentials (VEMP) (Colebatch & Halmagyi 1992; Colebatch et al. 1994). Some researchers have reported that airconducted skull tap elicits both saccular and utricle VEMPs, while being faster and less irritating for the subjects (Curthoys et al. 2009, Wackym et al., 2012). However, it is not clear whether the skull tap and auditory tone burst elicit the same pattern of cortical activity. Both forms of stimulation target the otolith response, which provides a measurement of vestibular function independent from semicircular canals. This is of high importance for studying the vestibular disorders related to otolith deficits. Previous imaging studies have documented activity in the anterior and posterior insula, superior temporal gyrus, inferior parietal lobule, pre and post central gyri, inferior frontal gyrus, and the anterior cingulate cortex in response to different modes of vestibular stimulation (Bottini et al., 1994; Dieterich et al., 2003; Emri et al., 2003; Schlindwein et al., 2008; Janzen et al., 2008). Here we hypothesized that the skull tap elicits the similar pattern of cortical activity as the auditory tone burst. Subjects put on a set of MR compatible skull tappers and headphones inside the 3T GE scanner, while lying in supine position, with eyes closed. All subjects received both forms of the stimulation, however, the order of stimulation with auditory tone burst and air-conducted skull tap was counterbalanced across subjects. Pneumatically powered skull tappers were placed bilaterally on the cheekbones. The vibration of the cheekbone was transmitted to the vestibular cortex, resulting in vestibular response (Halmagyi et al., 1995). Auditory tone bursts were also delivered for comparison. To validate

  5. Alcohol odor elicits appetitive facial expressions in human neonates prenatally exposed to the drug.

    PubMed

    Faas, Ana E; March, Samanta M; Moya, Pedro R; Molina, Juan C

    2015-09-01

    OH-Lem-EtOH sequence) and c) when merging both samples of babies, a positive and significant correlation was found between overall maternal absolute alcohol consumption per month and frequency of appetitive facial expressions elicited by alcohol odor. In conjunction with previous preclinical research, the present results indicate that human prenatal exposure to the drug that yields no evident teratological effects is sufficient to modify the hedonic value of alcohol's chemosensory attributes.

  6. Comparative Analysis of AhR-Mediated TCDD-Elicited Gene Expression in Human Liver Adult Stem Cells

    PubMed Central

    Kim, Suntae; Dere, Edward; Burgoon, Lyle D.; Chang, Chia-Cheng; Zacharewski, Timothy R.

    2009-01-01

    Time course and dose-response studies were conducted in HL1-1 cells, a human liver cell line with stem cell–like characteristics, to assess the differential gene expression elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) compared with other established models. Cells were treated with 0.001, 0.01, 0.1, 1, 10, or 100nM TCDD or dimethyl sulfoxide vehicle control for 12 h for the dose-response study, or with 10nM TCDD or vehicle for 1, 2, 4, 8, 12, 24, or 48 h for the time course study. Elicited changes were monitored using a human cDNA microarray with 6995 represented genes. Empirical Bayes analysis identified 144 genes differentially expressed at one or more time points following treatment. Most genes exhibited dose-dependent responses including CYP1A1, CYP1B1, ALDH1A3, and SLC7A5 genes. Comparative analysis of HL1-1 differential gene expression to human HepG2 data identified 74 genes with comparable temporal expression profiles including 12 putative primary responses. HL1-1–specific changes were related to lipid metabolism and immune responses, consistent with effects elicited in vivo. Furthermore, comparative analysis of HL1-1 cells with mouse Hepa1c1c7 hepatoma cell lines and C57BL/6 hepatic tissue identified 18 and 32 commonly regulated orthologous genes, respectively, with functions associated with signal transduction, transcriptional regulation, metabolism and transport. Although some common pathways are affected, the results suggest that TCDD elicits species- and model-specific gene expression profiles. PMID:19684285

  7. Functional Imaging of Human Vestibular Cortex Activity Elicited by Skull Tap and Auditory Tone Burst

    NASA Technical Reports Server (NTRS)

    Noohi, F.; Kinnaird, C.; Wood, S.; Bloomberg, J.; Mulavara, A.; Seidler, R.

    2016-01-01

    The current study characterizes brain activation in response to two modes of vestibular stimulation: skull tap and auditory tone burst. The auditory tone burst has been used in previous studies to elicit either the vestibulo-spinal reflex (saccular-mediated colic Vestibular Evoked Myogenic Potentials (cVEMP)), or the ocular muscle response (utricle-mediated ocular VEMP (oVEMP)). Some researchers have reported that air-conducted skull tap elicits both saccular and utricle-mediated VEMPs, while being faster and less irritating for the subjects. However, it is not clear whether the skull tap and auditory tone burst elicit the same pattern of cortical activity. Both forms of stimulation target the otolith response, which provides a measurement of vestibular function independent from semicircular canals. This is of high importance for studying otolith-specific deficits, including gait and balance problems that astronauts experience upon returning to earth. Previous imaging studies have documented activity in the anterior and posterior insula, superior temporal gyrus, inferior parietal lobule, inferior frontal gyrus, and the anterior cingulate cortex in response to different modes of vestibular stimulation. Here we hypothesized that skull taps elicit similar patterns of cortical activity as the auditory tone bursts, and previous vestibular imaging studies. Subjects wore bilateral MR compatible skull tappers and headphones inside the 3T GE scanner, while lying in the supine position, with eyes closed. Subjects received both forms of the stimulation in a counterbalanced fashion. Pneumatically powered skull tappers were placed bilaterally on the cheekbones. The vibration of the cheekbone was transmitted to the vestibular system, resulting in the vestibular cortical response. Auditory tone bursts were also delivered for comparison. To validate our stimulation method, we measured the ocular VEMP outside of the scanner. This measurement showed that both skull tap and auditory

  8. Mirth and laughter elicited by electrical stimulation of the human anterior cingulate cortex.

    PubMed

    Caruana, Fausto; Avanzini, Pietro; Gozzo, Francesca; Francione, Stefano; Cardinale, Francesco; Rizzolatti, Giacomo

    2015-10-01

    Laughter is a complex motor behavior that, typically, expresses mirth. Despite its fundamental role in social life, knowledge about the neural basis of laughter is very limited and mostly based on a few electrical stimulation (ES) studies carried out in epileptic patients. In these studies laughter was elicited from temporal areas where it was accompanied by mirth and from frontal areas plus an anterior cingulate case where laughter without mirth was observed. On the basis of these findings, it has been proposed a dichotomy between temporal lobe areas processing the emotional content of laughter and anterior cingulate cortex (ACC) and motor areas responsible of laughter production. The present study is aimed to understand the role of ACC in laughter. We report the effects of stimulation of 10 rostral, pregenual ACC (pACC) patients in which the ES elicited laughter. In half of the patients ES elicited a clear burst of laughter with mirth, while in the other half mirth was not evident. This large dataset allow us to offer a more reliable picture of the functional contribute of this region in laughter, and to precisely localize it in the cingulate cortex. We conclude that the pACC is involved in both the motor and the affective components of emotions, and challenge the validity of a sharp dichotomy between motor and emotional centers for laughing. Finally, we suggest a possible anatomical network for the production of positive emotional expressions.

  9. Spontaneous variation of anal "resting" pressure in healthy humans.

    PubMed

    Enck, P; Eggers, E; Koletzko, S; Erckenbrecht, J F

    1991-11-01

    To investigate anal sphincter performance during sleep and after a meal, a two-channel micro-transducer probe was used for 12-h stationary recording of basal anal pressure overnight in eight healthy male volunteers. It was shown that the basal anal pressure ("resting" pressure) exhibits three distinct patterns of cyclic activity changes in all subjects: a long-term rhythm with a prominent decrease of pressure during which sleep was approximately circadian, an ultradian rhythm of approximately 20 to 40 min in length that was more prominent at night, and spontaneous relaxations of the sphincter tone occurring between 3 and 20 times per hour with the maximum frequency after breakfast. These data indicate that the anal sphincter is a dynamic structure not often at rest. Long-term anorectal manometry may be supplementary to short-term clinical evaluation of anal sphincter performance in healthy subjects as well as in patients with defecation disorders.

  10. Fast transient networks in spontaneous human brain activity

    PubMed Central

    Baker, Adam P; Brookes, Matthew J; Rezek, Iead A; Smith, Stephen M; Behrens, Timothy; Probert Smith, Penny J; Woolrich, Mark

    2014-01-01

    To provide an effective substrate for cognitive processes, functional brain networks should be able to reorganize and coordinate on a sub-second temporal scale. We used magnetoencephalography recordings of spontaneous activity to characterize whole-brain functional connectivity dynamics at high temporal resolution. Using a novel approach that identifies the points in time at which unique patterns of activity recur, we reveal transient (100–200 ms) brain states with spatial topographies similar to those of well-known resting state networks. By assessing temporal changes in the occurrence of these states, we demonstrate that within-network functional connectivity is underpinned by coordinated neuronal dynamics that fluctuate much more rapidly than has previously been shown. We further evaluate cross-network interactions, and show that anticorrelation between the default mode network and parietal regions of the dorsal attention network is consistent with an inability of the system to transition directly between two transient brain states. DOI: http://dx.doi.org/10.7554/eLife.01867.001 PMID:24668169

  11. Fast transient networks in spontaneous human brain activity.

    PubMed

    Baker, Adam P; Brookes, Matthew J; Rezek, Iead A; Smith, Stephen M; Behrens, Timothy; Probert Smith, Penny J; Woolrich, Mark

    2014-03-25

    To provide an effective substrate for cognitive processes, functional brain networks should be able to reorganize and coordinate on a sub-second temporal scale. We used magnetoencephalography recordings of spontaneous activity to characterize whole-brain functional connectivity dynamics at high temporal resolution. Using a novel approach that identifies the points in time at which unique patterns of activity recur, we reveal transient (100-200 ms) brain states with spatial topographies similar to those of well-known resting state networks. By assessing temporal changes in the occurrence of these states, we demonstrate that within-network functional connectivity is underpinned by coordinated neuronal dynamics that fluctuate much more rapidly than has previously been shown. We further evaluate cross-network interactions, and show that anticorrelation between the default mode network and parietal regions of the dorsal attention network is consistent with an inability of the system to transition directly between two transient brain states. DOI: http://dx.doi.org/10.7554/eLife.01867.001.

  12. Engineered proteins detect spontaneous DNA breakage in human and bacterial cells

    PubMed Central

    Shee, Chandan; Cox, Ben D; Gu, Franklin; Luengas, Elizabeth M; Joshi, Mohan C; Chiu, Li-Ya; Magnan, David; Halliday, Jennifer A; Frisch, Ryan L; Gibson, Janet L; Nehring, Ralf Bernd; Do, Huong G; Hernandez, Marcos; Li, Lei; Herman, Christophe; Hastings, PJ; Bates, David; Harris, Reuben S; Miller, Kyle M; Rosenberg, Susan M

    2013-01-01

    Spontaneous DNA breaks instigate genomic changes that fuel cancer and evolution, yet direct quantification of double-strand breaks (DSBs) has been limited. Predominant sources of spontaneous DSBs remain elusive. We report synthetic technology for quantifying DSBs using fluorescent-protein fusions of double-strand DNA end-binding protein, Gam of bacteriophage Mu. In Escherichia coli GamGFP forms foci at chromosomal DSBs and pinpoints their subgenomic locations. Spontaneous DSBs occur mostly one per cell, and correspond with generations, supporting replicative models for spontaneous breakage, and providing the first true breakage rates. In mammalian cells GamGFP—labels laser-induced DSBs antagonized by end-binding protein Ku; co-localizes incompletely with DSB marker 53BP1 suggesting superior DSB-specificity; blocks resection; and demonstrates DNA breakage via APOBEC3A cytosine deaminase. We demonstrate directly that some spontaneous DSBs occur outside of S phase. The data illuminate spontaneous DNA breakage in E. coli and human cells and illustrate the versatility of fluorescent-Gam for interrogation of DSBs in living cells. DOI: http://dx.doi.org/10.7554/eLife.01222.001 PMID:24171103

  13. Vaccination with a recombinant protein encoding the tumor-specific antigen NY-ESO-1 elicits an A2/157-165-specific CTL repertoire structurally distinct and of reduced tumor reactivity than that elicited by spontaneous immune responses to NY-ESO-1-expressing Tumors.

    PubMed

    Bioley, Gilles; Guillaume, Philippe; Luescher, Immanuel; Bhardwaj, Nina; Mears, Gregory; Old, Lloyd; Valmori, Danila; Ayyoub, Maha

    2009-01-01

    In a recent vaccination trial assessing the immunogenicity of an NY-ESO-1 (ESO) recombinant protein administered with Montanide and CpG, we have obtained evidence that this vaccine induces specific cytolytic T lymphocytes (CTL) in half of the patients. Most vaccine-induced CTLs were directed against epitopes located in the central part of the protein, between amino acids 81 and 110. This immunodominant region, however, is distinct from another ESO CTL region, 157-165, that is a frequent target of spontaneous CTL responses in A2+ patients bearing ESO tumors. In this study, we have investigated the CTL responses to ESO 157-165 in A2+ patients vaccinated with the recombinant protein. Our data indicate that after vaccination with the protein, CTL responses to ESO 157-165 are induced in some, but not all, A2+ patients. ESO 157-165-specific CTLs induced by vaccination with the ESO protein were functionally heterogeneous in terms of tumor recognition and often displayed decreased tumor reactivity as compared with ESO 157-165-specific CTLs isolated from patients with spontaneous immune responses to ESO. Remarkably, protein-induced CTLs used T-cell receptors similar to those previously isolated from patients vaccinated with synthetic ESO peptides (Vbeta4.1) and distinct from those used by highly tumor-reactive CTLs isolated from patients with spontaneous immune responses (Vbeta1.1, Vbeta8.1, and Vbeta13.1). Together, these results demonstrate that vaccination with the ESO protein elicits a repertoire of ESO 157-165-specific CTLs bearing T-cell receptors that are structurally distinct from those of CTLs found in spontaneous immune responses to the antigen and that are heterogeneous in terms of tumor reactivity, being often poorly tumor reactive.

  14. Phosphodiesterases reduce spontaneous sinoatrial beating but not the 'fight or flight' tachycardia elicited by agonists through Gs-protein-coupled receptors.

    PubMed

    Kaumann, Alberto J

    2011-07-01

    Cyclic AMP (cAMP) steers the generation of basal heart beat in the sinoatrial node. It also induces sinoatrial tachycardia and increased cardiac force, elicited through activation of Gs-protein-coupled receptors (GsPCRs). Phosphodiesterases (PDEs) hydrolyse cAMP. In the heart mainly PDE3 and PDE4 would be expected to limit those functions, and the PDE isoenzymes do indeed reduce basal sinoatrial beating rate and blunt the positive inotropic effects of agonists, mediated by GsPCRs. By contrast, recent evidence shows that GsPCR-mediated sinoatrial tachycardia is not controlled by PDE1-5. A PDE-resistant cAMP pool in sinoatrial cells, generated through activation of GsPCRs, including β(1)- and β(2)-adrenoceptors, appears to guarantee unrestrained tachycardia during fight or flight stress.

  15. Ludic Elicitation: Using Games for Knowledge Elicitation

    ERIC Educational Resources Information Center

    Cao, Yan

    2014-01-01

    Knowledge elicitation from human beings is important for many fields, such as decision support systems, risk communication, and customer preference studying. Traditional approaches include observations, questionnaires, structured and semi-structured interviews, and group discussions. Many publications have been studying different techniques for a…

  16. Spontaneous Recovery of Human Spatial Memory in a Virtual Water Maze

    ERIC Educational Resources Information Center

    Luna, David; Martínez, Héctor

    2015-01-01

    The occurrence of spontaneous recovery in human spatial memory was assessed using a virtual environment. In Experiment 1, spatial memory was established by training participants to locate a hidden platform in a virtual water maze using a set of four distal landmarks. In Experiment 2, after learning about the location of a hidden platform, the…

  17. Compound Stimulus Extinction Reduces Spontaneous Recovery in Humans

    ERIC Educational Resources Information Center

    Coelho, Cesar A. O.; Dunsmoor, Joseph E.; Phelps, Elizabeth A.

    2015-01-01

    Fear-related behaviors are prone to relapse following extinction. We tested in humans a compound extinction design ("deepened extinction") shown in animal studies to reduce post-extinction fear recovery. Adult subjects underwent fear conditioning to a visual and an auditory conditioned stimulus (CSA and CSB, respectively) separately…

  18. Spontaneous pregnancy loss in humans and exposure to arsenic in drinking water.

    PubMed

    Bloom, Michael S; Fitzgerald, Edward F; Kim, Keewan; Neamtiu, Iulia; Gurzau, Eugen S

    2010-11-01

    Maternal exposure to high concentrations of inorganic arsenic (iAs) in naturally contaminated drinking groundwater sources has been associated with an increased risk for the spontaneous loss of clinically recognized pregnancies in several epidemiologic studies. Whereas a large worldwide population depends on drinking groundwater sources with high levels of iAs contamination, in quantities exceeding 10 parts per billion (ppb), an even larger population is likely to be exposed to mild-moderate drinking groundwater iAs contamination, in quantities <10ppb. Only a single epidemiologic study to date has considered spontaneous pregnancy loss in association with consumption of drinking water with mild-moderate iAs contamination; the vast majority of published studies of spontaneous loss addressed populations with substantial exposure. The aim of this review is to evaluate the published literature to assess the plausibility for a causal association between exposure to iAs-contaminated drinking water and the spontaneous loss of clinically recognized pregnancy. In spite of numerous methodologic limitations resulting from circumstance or design, a consistent pattern of increased risk for loss is suggested by the epidemiologic literature. Moreover, these study results are corroborated by a large number of experimental studies, albeit usually conducted at concentrations exceeding that to which humans are exposed via contaminated drinking water. In this review, we discuss sources of human iAs exposure, highlight several experimental studies pertinent to a possible causal link between iAs and spontaneous pregnancy loss in humans, and provide a critical review of published epidemiologic studies of pregnancy loss and drinking water iAs exposures, and their limitations. Based on a review of the published literature, we recommend the future conduct of a two-stage comprehensive prospective study of low-moderate iAs drinking water exposure and spontaneous pregnancy loss.

  19. Compound stimulus extinction reduces spontaneous recovery in humans.

    PubMed

    Coelho, Cesar A O; Dunsmoor, Joseph E; Phelps, Elizabeth A

    2015-12-01

    Fear-related behaviors are prone to relapse following extinction. We tested in humans a compound extinction design ("deepened extinction") shown in animal studies to reduce post-extinction fear recovery. Adult subjects underwent fear conditioning to a visual and an auditory conditioned stimulus (CSA and CSB, respectively) separately paired with an electric shock. The target CS (CSA) was extinguished alone followed by compound presentations of the extinguished CSA and nonextinguished CSB. Recovery of conditioned skin conductance responses to CSA was reduced 24 h after compound extinction, as compared with a group who received an equal number of extinction trials to the CSA alone. PMID:26572649

  20. Compound stimulus extinction reduces spontaneous recovery in humans.

    PubMed

    Coelho, Cesar A O; Dunsmoor, Joseph E; Phelps, Elizabeth A

    2015-12-01

    Fear-related behaviors are prone to relapse following extinction. We tested in humans a compound extinction design ("deepened extinction") shown in animal studies to reduce post-extinction fear recovery. Adult subjects underwent fear conditioning to a visual and an auditory conditioned stimulus (CSA and CSB, respectively) separately paired with an electric shock. The target CS (CSA) was extinguished alone followed by compound presentations of the extinguished CSA and nonextinguished CSB. Recovery of conditioned skin conductance responses to CSA was reduced 24 h after compound extinction, as compared with a group who received an equal number of extinction trials to the CSA alone.

  1. Decreased type V collagen expression in human decidual tissues of spontaneous abortion during early pregnancy.

    PubMed Central

    Iwahashi, M; Nakano, R

    1998-01-01

    AIM: To provide some insight into the aetiology of spontaneous abortion, the contents of type V collagen was investigated in human decidual tissues in spontaneous abortion and normal pregnancy. METHODS: Collagens were extracted from decidual tissues in spontaneous abortion (n = 19) and normal pregnancy (n = 25). The different types of collagen alpha chains were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), stained with Coomassie brilliant blue, and measured by densitometry. The relative amounts of the alpha 1 (III) and alpha 1 (V) chains were calculated by dividing the band intensities of the alpha 1 (III) and alpha 1 (V) chains by that of the alpha 1 (I) chain. RESULTS: The ratio of the alpha 1 (V) chain to that of the alpha 1 (I) chain in decidual tissues in spontaneous abortion was significantly lower than that found in normal pregnancy (p < 0.05). CONCLUSIONS: These results suggest that type V collagen might play an important role in the maintenance of pregnancy and that decreased expression of this collagen could be associated with spontaneous abortion. Images PMID:9577371

  2. Distributions of spontaneous chromosomal aberrations and of spontaneous and induced SCE and micronuclei in peripheral lymphocytes from a human population

    SciTech Connect

    Bender, M.A.; Setlow, R.B.

    1992-12-31

    Biomonitoring of human populations for exposure to genotoxic/clastogenic agents in the environment or the workplace must depend upon statistical tests for elevations in the frequencies of the biological endpoints being monitored, usually chromosomal aberrations (CA), micronuclei (MN), or sister chromatid exchanges (SCE) in peripheral blood lymphocytes. Statistical tests are based, in turn, upon certain assumptions regarding the distribution of the test statistic. When they are often not recognized as such, tests of significance can be in error, and any conclusion drawn that there is or is not a statistically significant difference between one population sample and another maybe erroneous. In population monitoring this means either false negatives or false positives can result and it is hard to know which is worse. Furthermore, even the intelligent design of studies whose object is to test for an elevated level in an exposed population must depend upon prior knowledge of the nature of both spontaneous and induced response; if variance is large enough, a given-sized study might be inconclusive, and an adequate study simply too large-to be practical.

  3. Distributions of spontaneous chromosomal aberrations and of spontaneous and induced SCE and micronuclei in peripheral lymphocytes from a human population

    SciTech Connect

    Bender, M.A.; Setlow, R.B.

    1992-01-01

    Biomonitoring of human populations for exposure to genotoxic/clastogenic agents in the environment or the workplace must depend upon statistical tests for elevations in the frequencies of the biological endpoints being monitored, usually chromosomal aberrations (CA), micronuclei (MN), or sister chromatid exchanges (SCE) in peripheral blood lymphocytes. Statistical tests are based, in turn, upon certain assumptions regarding the distribution of the test statistic. When they are often not recognized as such, tests of significance can be in error, and any conclusion drawn that there is or is not a statistically significant difference between one population sample and another maybe erroneous. In population monitoring this means either false negatives or false positives can result and it is hard to know which is worse. Furthermore, even the intelligent design of studies whose object is to test for an elevated level in an exposed population must depend upon prior knowledge of the nature of both spontaneous and induced response; if variance is large enough, a given-sized study might be inconclusive, and an adequate study simply too large-to be practical.

  4. Low volume-high intensity interval exercise elicits antioxidant and anti-inflammatory effects in humans.

    PubMed

    Wadley, Alex J; Chen, Yu-Wen; Lip, Gregory Y H; Fisher, James P; Aldred, Sarah

    2016-01-01

    The purpose of the present study was to compare acute changes in oxidative stress and inflammation in response to steady state and low volume, high intensity interval exercise (LV-HIIE). Untrained healthy males (n = 10, mean ± s: age 22 ± 3 years; VO2MAX 42.7 ± 5.0 ml · kg(-1) · min(-1)) undertook three exercise bouts: a bout of LV-HIIE (10 × 1 min 90% VO2MAX intervals) and two energy-matched steady-state cycling bouts at a moderate (60% VO2MAX; 27 min, MOD) and high (80% VO2MAX; 20 min, HIGH) intensity on separate days. Markers of oxidative stress, inflammation and physiological stress were assessed before, at the end of exercise and 30 min post-exercise (post+30). At the end of all exercise bouts, significant changes in lipid hydroperoxides (LOOH) and protein carbonyls (PCs) (LOOH (nM): MOD +0.36; HIGH +3.09; LV-HIIE +5.51 and PC (nmol · mg(-1) protein): MOD -0.24; HIGH -0.11; LV-HIIE -0.37) were observed. Total antioxidant capacity (TAC) increased post+30, relative to the end of all exercise bouts (TAC (µM): MOD +189; HIGH +135; LV-HIIE +102). Interleukin (IL)-6 and IL-10 increased post+30 in HIGH and LV-HIIE only (P < 0.05). HIGH caused the greatest lymphocytosis, adrenaline and cardiovascular response (P < 0.05). At a reduced energy cost and physiological stress, LV-HIIE elicited similar cytokine and oxidative stress responses to HIGH.

  5. Gene deleted live attenuated Leishmania vaccine candidates against visceral leishmaniasis elicit pro-inflammatory cytokines response in human PBMCs.

    PubMed

    Avishek, Kumar; Kaushal, Himanshu; Gannavaram, Sreenivas; Dey, Ranadhir; Selvapandiyan, Angamuthu; Ramesh, V; Negi, Narender Singh; Dubey, Uma S; Nakhasi, Hira L; Salotra, Poonam

    2016-01-01

    Currently no effective vaccine is available for human visceral leishmaniasis(VL) caused by Leishmania donovani. Previously, we showed that centrin1 and p27gene deleted live attenuated Leishmania parasites (LdCen1(-/-) and Ldp27(-/-)) are safe, immunogenic and protective in animal models. Here, to assess the correlates of protection, we evaluated immune responses induced by LdCen1(-/-) and Ldp27(-/-) in human blood samples obtained from healthy, healed VL (HVL), post kala-azar dermal leishmaniasis(PKDL) and VL subjects. Both parasites infected human macrophages, as effectively as the wild type parasites. Further, LdCen1(-/-) and Ldp27(-/-) strongly stimulated production of pro-inflammatory cytokines including, IL-12, IFN-γ, TNF-α, IL-2, IL-6 and IL-17 in the PBMCs obtained from individuals with a prior exposure to Leishmania (HVL and PKDL). There was no significant stimulation of anti-inflammatory cytokines (IL-4 and IL-10). Induction of Th1 biased immune responses was supported by a remarkable increase in IFN-γ secreting CD4(+) and CD8(+) T cells and IL-17 secreting CD4(+) cells in PBMCs from HVL cases with no increase in IL-10 secreting T cells. Hence, LdCen1(-/-) and Ldp27(-/-) are promising as live vaccine candidates against VL since they elicit strong protective immune response in human PBMCs from HVL, similar to the wild type parasite infection, mimicking a naturally acquired protection following cure. PMID:27624408

  6. Immunization of simian immunodeficiency virus-infected rhesus monkeys with soluble human CD4 elicits an antiviral response.

    PubMed Central

    Watanabe, M; Levine, C G; Shen, L; Fisher, R A; Letvin, N L

    1991-01-01

    Since the CD4 molecule is a high-affinity cell-surface receptor for the human immunodeficiency virus (HIV), it has been suggested that a soluble truncated form of CD4 may compete with cell-surface CD4 for HIV binding and thus be of use in the therapy of AIDS. We have utilized the simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys to explore another possible therapeutic application of CD4 in AIDS--the use of recombinant soluble CD4 (rsCD4) as an immunogen. SIVmac-infected rhesus monkeys immunized with human rsCD4 developed not only an anti-human CD4 but also an anti-rhesus monkey CD4 antibody response. Coincident with the generation of this antibody response, SIVmac could not be isolated easily from peripheral blood lymphocytes and bone marrow macrophages of these animals. Furthermore, the decreased number of both granulocyte/macrophage and erythrocyte colonies grown from the bone marrow of these immunized monkeys rose to normal levels. These findings suggest that a modified human CD4 molecule serving as an immunogen might elicit an antibody response in man that could induce a beneficial therapeutic response in HIV-infected individuals. PMID:2052546

  7. Soluble human CD4 elicits an antibody response in rhesus monkeys that inhibits simian immunodeficiency virus replication

    SciTech Connect

    Watanabe, Mamoru; Chen, Zheng W.; Tsubota, Hiroshi; Lord, C.I.; Levine, C.G.; Letvin, N.L. )

    1991-01-01

    Rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIV{sub mac}) demonstrate significant virologic and clinical improvement as a result of treatment with human recombinant soluble CD4 (rsCD4). The authors show that human rsCD4 does not efficiently inhibit SIV{sub mac} replication in bone marrow macrophages of rhesus monkeys and does not significantly augment bone marrow hematopoietic colony formation in vitro. However, plasma of human rsCD4-treated rhesus monkeys does exhibit significant anti-SIV{sub mac} activity in vitro. Plasma of these animals efficiently blocks SIV{sub mac} replicaton in peripheral blood lymphocytes and bone marrow macrophages. It also increases granulocyte/macrophage colony formation in vitro by bone marrow cells of SIV{sub mac}-infected monkeys. This plasma and the IgG fraction of plasma from a rhesus monkey immunized with human rsCD4 in adjuvant demonstrate reactivity with a soluble form of the rhesus monkey CD4 molecule, exhibit binding to CD4{sup +} but not CD8{sup +} concanavalin A-activated rhesus monkey peripheral blood lymphocytes, and precipitate the CD4 molecule from surface-labeled activated rhesus monkey peripheral blood lymphocytes. Moreover, anti-viral activity is demonstrable in the IgG fraction of plasma from a human rsCD4-immunized monkey. These studies raise the possibility that a modified human CD4 molecule serving as an immunogen might elicit an antibody response that could potentially induce a beneficial therapeutic response in human immunodeficiency virus-infected individuals.

  8. Calcitonin Gene-Related Peptide Receptor Blocker Inhibits Spontaneous Activity of Human Ureter.

    PubMed

    Jankovic, Slobodan M; Jankovic, Snezana V; Stojadinovic, Dobrivoje; Stojadinovic, Miroslav; Djuric, Janko M; Stojic, Isidora

    2015-01-01

    Calcitonin gene-related peptide (CGRP) is present in nerve fibers that innervate the human ureter and may have important influence on the motility of this organ. The aim of our study was to investigate whether CGRP could affect the motility of an isolated human ureter. The tension and intraluminal pressure of the isolated ureteral segments were recorded and registered on a personal computer. Both phasic and tonic contractions of the isolated preparations were measured as area under the tension or pressure recordings. CGRP and CGRP fragment 8-37 were separately added to the organ baths in a cumulative way, thereby gradually increasing their concentration in the baths' solution. Alpha-CGRP did not affect either phasic, spontaneous activity or tone of isolated ureteral segments, as measured by both tension and intraluminal pressure. On the other hand, CGRP 8-37 caused concentration-dependent inhibition of spontaneous contractions of the isolated ureteral segments. PMID:26305057

  9. Spontaneous lesions in the reproductive tract and mammary gland of female non-human primates.

    PubMed

    Cooper, Timothy K; Gabrielson, Kathleen L

    2007-04-01

    Because of their close phylogenic relationship with humans, the use of non-human primates (NHP) as experimental subjects has a long history in biomedical research. Although research topics have shifted focus and species used have changed, NHP remain vital as models in basic and applied research. While there is a wealth of information available on the spontaneous lesions of NHP, most of this information is fragmented, dated, or narrow in focus, often limited to single case reports. This review attempts to integrate this information to illustrate and enumerate the spectrum of spontaneous pathology of the reproductive tract and mammary gland of NHP. Although not the focus of this review, steroid-related changes are inextricably linked to these tissues, and brief consideration is given to this subject as well. PMID:17342758

  10. Spontaneous secretion of interferon γ and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes

    PubMed Central

    Carol, M; Lambrechts, A; Van Gossum, A; Libin, M; Goldman, M; Mascart-Lemone, F

    1998-01-01

    Background—Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses. 
Aims—To quantify interferon γ (IFN-γ) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation. 
Patients—Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa. 
Methods—Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-γ and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT). 
Results—The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-γ (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-γ SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-γ and IL-4 were mainly produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-γ in the basal state, and 0.1% secreted IL-4. 
Conclusions—Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-γ and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases. 

 Keywords: intestinal lymphocytes; ELISPOT; interferon γ; interleukin 4 PMID:9659157

  11. MERS-CoV at the Animal–Human Interface: Inputs on Exposure Pathways from an Expert-Opinion Elicitation

    PubMed Central

    Funk, Anna L.; Goutard, Flavie Luce; Miguel, Eve; Bourgarel, Mathieu; Chevalier, Veronique; Faye, Bernard; Peiris, J. S. Malik; Van Kerkhove, Maria D.; Roger, Francois Louis

    2016-01-01

    Nearly 4 years after the first report of the emergence of Middle-East respiratory syndrome Coronavirus (MERS-CoV) and nearly 1800 human cases later, the ecology of MERS-CoV, its epidemiology, and more than risk factors of MERS-CoV transmission between camels are poorly understood. Knowledge about the pathways and mechanisms of transmission from animals to humans is limited; as of yet, transmission risks have not been quantified. Moreover the divergent sanitary situations and exposures to animals among populations in the Arabian Peninsula, where human primary cases appear to dominate, vs. other regions in the Middle East and Africa, with no reported human clinical cases and where the virus has been detected only in dromedaries, represents huge scientific and health challenges. Here, we have used expert-opinion elicitation in order to obtain ideas on relative importance of MERS-CoV risk factors and estimates of transmission risks from various types of contact between humans and dromedaries. Fourteen experts with diverse and extensive experience in MERS-CoV relevant fields were enrolled and completed an online questionnaire that examined pathways based on several scenarios, e.g., camels–camels, camels–human, bats/other species to camels/humans, and the role of diverse biological substances (milk, urine, etc.) and potential fomites. Experts believed that dromedary camels play the largest role in MERS-CoV infection of other dromedaries; however, they also indicated a significant influence of the season (i.e. calving or weaning periods) on transmission risk. All experts thought that MERS-CoV-infected dromedaries and asymptomatic humans play the most important role in infection of humans, with bats and other species presenting a possible, but yet undefined, risk. Direct and indirect contact of humans with dromedary camels were identified as the most risky types of contact, when compared to consumption of various camel products, with estimated “most likely

  12. Similarity of spontaneous germinal and in vitro somatic cell mutation rates in humans: implications for carcinogenesis and for the role of exogenous factors in "spontaneous" germinal mutagenesis.

    PubMed Central

    Kuick, R D; Neel, J V; Strahler, J R; Chu, E H; Bargal, R; Fox, D A; Hanash, S M

    1992-01-01

    The rate of spontaneous mutation resulting in electrophoretic variants per cell generation in a human lymphoblastoid cell line, on the basis of experiments described in this paper, is found to be 7.2 x 10(-8) per locus. A review of similar data on electrophoretic variants resulting from spontaneous mutation in the human germ line leads to an estimate of 3.3 x 10(-8) per locus per cell generation. It is argued that the similarity of these two estimates, despite an average cell generation time of 18.5 hr for the cultured somatic cells but about 26 days in the germ line, suggests that spontaneous mutation involving nucleotide substitutions is much more dependent on cell generation than on time. This finding permits the inference that environmental (exogenous) variables make a relatively small contribution to the rate of this type of human germinal spontaneous mutation. While in vitro somatic-cell mutation rates, such as derived in this study, provide a basis for modeling the contribution of nucleotide substitutions in multihit/clonal theories of carcinogenesis, it is also argued that the complex of events involved in carcinogenesis, including chromosomal rearrangements and mitotic recombination, could have very different individual probabilities. Estimates for the rates of these other types of mutation are needed to provide a better understanding of the manner in which multiple mutations accumulate in malignant cells. Images PMID:1495998

  13. Hazardous Metal Pollution in the Republic of Fiji and the Need to Elicit Human Exposure

    PubMed Central

    Park, Eun-Kee; Choi, Hyun-Ju; Wilson, Colleen Turaga; Ueno, Susumu

    2013-01-01

    The fact that hazardous metals do not bio-degrade or bio-deteriorate translates to long-lasting environmental effects. In the context of evidently rapid global industrialization, this ought to warrant serious caution, particularly in developing countries. In the Republic of Fiji, a developing country in the South Pacific, several different environmental studies over the past 20 years have shown levels of lead, copper, zinc and iron in sediments of the Suva Harbor to be 6.2, 3.9, 3.3 and 2.1 times more than the accepted background reference levels, respectively. High levels of mercury have also been reported in lagoon shellfish. These data inevitably warrant thorough assessment of the waste practices of industries located upstream from the estuaries, but in addition, an exposure and health impact assessment has never been conducted. Relevant government departments are duty-bound, at least to the general public that reside in and consume seafood from the vicinities of the Suva Harbor, to investigate possible human effects of the elevated hazardous metal concentrations found consistently in 20 years of surface sediment analysis. Furthermore, pollution of the intermediate food web with hazardous metals should be investigated, regardless of whether human effects are eventually confirmed present or not. PMID:24498594

  14. CTAB-coated gold nanorods elicit allergic response through degranulation and cell death in human basophils

    NASA Astrophysics Data System (ADS)

    Cheung, Ka Lun; Chen, Huanjun; Chen, Qiulan; Wang, Jianfang; Ho, Ho Pui; Wong, Chun Kwok; Kong, Siu Kai

    2012-07-01

    The effect of CTAB (cetyltrimethylammonium bromide)- or PEG (polyethylene glycol)-coated gold-nanorods (Au-NRs) on the non-IgE mediated allergic response was studied. We found that the CTAB-Au-NRs released more allergic mediators such as histamine and β-hexosaminidase from human basophil KU812, a common model for studying allergy, after 20 min incubation. Also, the CTAB-Au-NRs induced more apoptosis than the PEG-Au-NRs in KU812 24 h after treatment. These short- and long-term effects were not solely due to the CTAB residues in the supernatant desorbed from the Au-NRs.The effect of CTAB (cetyltrimethylammonium bromide)- or PEG (polyethylene glycol)-coated gold-nanorods (Au-NRs) on the non-IgE mediated allergic response was studied. We found that the CTAB-Au-NRs released more allergic mediators such as histamine and β-hexosaminidase from human basophil KU812, a common model for studying allergy, after 20 min incubation. Also, the CTAB-Au-NRs induced more apoptosis than the PEG-Au-NRs in KU812 24 h after treatment. These short- and long-term effects were not solely due to the CTAB residues in the supernatant desorbed from the Au-NRs. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr30435j

  15. Gene networks related to the cell death elicited by hyperthermia in human oral squamous cell carcinoma HSC-3 cells.

    PubMed

    Tabuchi, Yoshiaki; Wada, Shigehito; Furusawa, Yukihiro; Ohtsuka, Kenzo; Kondo, Takashi

    2012-03-01

    Local hyperthermia (HT) for various types of malignant tumors has shown promising antitumor effects. To confirm the detailed molecular mechanism underlying cell death induced by HT, gene expression patterns and gene networks in human oral squamous cell carcinoma (OSCC) cells were examined using a combination of DNA microarray and bioinformatics tools. OSCC HSC-3 cells were treated with HT at 44˚C for 90 min or mild hyperthermia (MHT) at 42˚C for 90 min, followed by culturing at 37˚C for 0-24 h. Treatment of cells with HT prevented cell proliferation (62%) and induced cell death (17%), whereas these alterations were not observed in cells treated with MHT. Microarray analysis revealed substantial differences with respect to gene expression patterns and biological function for the two different hyperthermic treatments. Moreover, we identified the temperature-specific gene networks D and H that were obtained from significantly up-regulated genes in the HT and MHT conditions, respectively, using Ingenuity pathway analysis tools. Gene network D, which contains 14 genes such as ATF3, DUSP1 and JUN, was associated with relevant biological functions including cell death and cellular movement. Gene network H, which contains 13 genes such as BAG3, DNAJB1 and HSPA1B, was associated with cellular function and maintenance and cellular assembly and organization. These findings provide a basis for understanding the detailed molecular mechanisms of cell death elicited by HT in human OSCC cells. PMID:22179328

  16. Gene deleted live attenuated Leishmania vaccine candidates against visceral leishmaniasis elicit pro-inflammatory cytokines response in human PBMCs

    PubMed Central

    Avishek, Kumar; Kaushal, Himanshu; Gannavaram, Sreenivas; Dey, Ranadhir; Selvapandiyan, Angamuthu; Ramesh, V.; Negi, Narender Singh; Dubey, Uma S.; Nakhasi, Hira L.; Salotra, Poonam

    2016-01-01

    Currently no effective vaccine is available for human visceral leishmaniasis(VL) caused by Leishmania donovani. Previously, we showed that centrin1 and p27gene deleted live attenuated Leishmania parasites (LdCen1−/− and Ldp27−/−) are safe, immunogenic and protective in animal models. Here, to assess the correlates of protection, we evaluated immune responses induced by LdCen1−/− and Ldp27−/− in human blood samples obtained from healthy, healed VL (HVL), post kala-azar dermal leishmaniasis(PKDL) and VL subjects. Both parasites infected human macrophages, as effectively as the wild type parasites. Further, LdCen1−/− and Ldp27−/− strongly stimulated production of pro-inflammatory cytokines including, IL-12, IFN-γ, TNF-α, IL-2, IL-6 and IL-17 in the PBMCs obtained from individuals with a prior exposure to Leishmania (HVL and PKDL). There was no significant stimulation of anti-inflammatory cytokines (IL-4 and IL-10). Induction of Th1 biased immune responses was supported by a remarkable increase in IFN-γ secreting CD4+ and CD8+ T cells and IL-17 secreting CD4+ cells in PBMCs from HVL cases with no increase in IL-10 secreting T cells. Hence, LdCen1−/− and Ldp27−/− are promising as live vaccine candidates against VL since they elicit strong protective immune response in human PBMCs from HVL, similar to the wild type parasite infection, mimicking a naturally acquired protection following cure. PMID:27624408

  17. Photocytotoxicity in human dermal fibroblasts elicited by permanent makeup inks containing titanium dioxide.

    PubMed

    Wamer, Wayne G; Yin, Jun-Jie

    2011-01-01

    Titanium dioxide (TiO2) is a pigment widely used in decorative tattoo and permanent makeup inks. However, little is known about the risks associated with its presence in these products. We have developed an in vitro assay to identify inks containing TiO2 that are cytotoxic and/or photocytotoxic. The presence of TiO2 in ten permanent makeup inks was established by X-ray fluorescence. Using X-ray diffraction, we found that seven inks contained predominately TiO2 (anatase), the more photocatalytically active crystalline form of TiO2. The remaining inks contained predominately TiO2 (rutile). To identify cytotoxic and/or photocytotoxic inks, human dermal fibroblasts were incubated for 18 h in media containing inks or pigments isolated from inks. Fibroblasts were then irradiated with 10 J/cm2 UVA radiation combined with 45 J/cm2 visible light for determining photocytotoxicity, or kept in the dark for determining cytotoxicity. Toxicity was assessed as inhibition of colony formation. No inks were cytotoxic. However eight inks, and the pigments isolated from these inks, were photocytotoxic. Using ESR, we found that most pigments from photocytotoxic inks generated hydroxyl radicals when photoexcited with UV radiation. Therefore, the possibility of photocytotoxicity should be considered when evaluating the safety of permanent makeup inks containing TiO2.

  18. Myoelectric activity along human gastrocnemius medialis: different spatial distributions of postural and electrically elicited surface potentials.

    PubMed

    Hodson-Tole, Emma F; Loram, Ian D; Vieira, Taian M M

    2013-02-01

    It has recently been shown that motor units in human medial gastrocnemius (MG), activated during standing, occupy relatively small territories along the muscle's longitudinal axis. Such organisation provides potential for different motor tasks to produce differing regional patterns of activity. Here, we investigate whether postural control and nerve electrical stimulation produce equal longitudinal activation patterns in MG. Myoelectric activity, at different proximal-distal locations of MG, was recorded using a linear electrode array. To ensure differences in signal amplitude between channels did not result from local, morphological factors two experimental protocols were completed: (i) quiet standing; (ii) electrical stimulation of the tibial nerve. Averaged, rectified values (ARVs) were calculated for each channel in each condition. The distribution of signals along electrode channels was described using linear regression and differences between protocols at each channel determined as the ratio between mean ARV from standing: stimulation protocols. Ratio values changed systematically across electrode channels in seven (of eight) participants, with larger values in distal channels. The distribution of ARV along MG therefore differed between experimental conditions. Compared to fibres of units activated during MG nerve stimulation, units activated during standing may have a tendency to be more highly represented in the distal muscle portion. PMID:22967836

  19. Spontaneous contractility of human placental vessels in vitro axipetal and isometric recording.

    PubMed

    Gonzalez Panizza, V H; Benedetti, W L; Alvarez, H

    1980-01-01

    In vitro contractility of isolated cylindrical segments of chorial arteries and veins from 40 human term placentas was studied. Contractility was recorded by an isometrical and axipetal method. Spontaneous contractility was observed in 75% of the arteries and in 45% of veins. In both types of vessels, contractility was similar and characterized by development of tonic circumferential tension, between 100 and 200 mg/mm. Clonic activity consisting of rhythmic contractions with an average frequency between 0.7 and 0.9/min and an average intensity of 5--40 mg/min was superimposed. Vasoconstrictor drugs (PGF2 alpha, histamine and adrenaline) increase tonic tension without modifying the frequency of clonic activity. It is suggested that spontaneous contractility may be the expression of myogenic excitability related to the regulation of fetal placental blood flow.

  20. Antioxidative and cytoprotective response elicited by molybdenum nanoparticles in human cells.

    PubMed

    Akhtar, Mohd Javed; Ahamed, Maqusood; Alhadlaq, Hisham A; Alshamsan, Aws; Khan, M A Majeed; Alrokayan, Salman A

    2015-11-01

    Nanotechnology based therapeutics can offer an alternative platform in a wide variety of biomedical applications. Here we report novel cytotoxicity preventive potential of molybdenum nanoparticles (Mo NPs) in human breast (MCF-7) and fibrosarcoma (HT-1080) cells compromised with oxidant exposure. Physicochemical properties such as size, crystallinity, purity and band gap (an optical characteristic) of Mo NPs were characterized respectively by field emission transmission electron microscopy (FETEM), X-ray diffraction (XRD), energy dispersive spectrum (EDS) and UV-vis absorption spectroscopy. The average size of crystalline Mo NPs was found to be 35 nm with a band gap of 1.4 eV. Potential cytotoxicity of Mo NPs was evaluated by a battery of cell viability and oxidative stress parameters. Cell viability and oxidative stress data suggested Mo NPs to be reasonably non-cytotoxic. Cytotoxic preventive and GSH restoring potential of Mo NPs was determined against cytotoxicity and oxidative stress induced by H2O2 (and ZnO NPs) in two cells. Mo NPs significantly increased GSH level in MCF-7 and HT-1080 cells, an activity that was comparable to antioxidant N-acetyl cysteine (NAC). GSH level was increased 1.56 times in MCF-7 cells and 1.25 times in HT-1080 cells by 100 μg/ml of Mo NPs relative to control cells in 24 h. End-point data clearly suggest that Mo NPs significantly protected cells against cytotoxicity induced by H2O2 and ZnO (NPs) (p<0.05). Our study warrants further investigation about Mo NPs that could be exploited in myriads of nanotechnology applications.

  1. Recombinant tandem multi-linear neutralizing epitopes of human enterovirus 71 elicited protective immunity in mice

    PubMed Central

    2014-01-01

    Background Human Enterovirus 71 (EV71) has emerged as the leading cause of viral encephalitis in children, especially in the Asia-Pacific regions. EV71 vaccine development is of high priority at present, and neutralization antibodies have been documented to play critical roles during in vitro and in vivo protection against EV71 infection. Results In this study, a novel strategy to produce EV71 vaccine candidate based on recombinant multiple tandem linear neutralizing epitopes (mTLNE) was proposed. The three well identified EV71 linear neutralizing epitopes in capsid proteins, VP1-SP55, VP1-SP70 and VP2-SP28, were sequentially linked by a Gly-Ser linker ((G4S)3), and expressed in E.coli in fusion with the Trx and His tag at either terminal. The recombinant protein mTLNE was soluble and could be purified by standard affinity chromatography. Following three dosage of immunization in adult mice, EV71-specific IgG and neutralization antibodies were readily induced by recombinant mTLNE. IgG subtyping demonstrated that lgG1 antibodies dominated the mTLNE-induced humoral immune response. Especially, cytokine profiling in spleen cells from the mTLNE-immunized mice revealed high production of IL-4 and IL-6. Finally, in vivo challenge experiments showed that passive transfer with anti-mTLNE sera conferred full protection against lethal EV71 challenge in neonatal mice. Conclusion Our results demonstrated that this rational designed recombinant mTLNE might have the potential to be further developed as an EV71 vaccine in the future. PMID:24885030

  2. Repetitive speech elicits widespread deactivation in the human cortex: the “Mantra” effect?

    PubMed Central

    Berkovich-Ohana, Aviva; Wilf, Meytal; Kahana, Roni; Arieli, Amos; Malach, Rafael

    2015-01-01

    Background Mantra (prolonged repetitive verbal utterance) is one of the most universal mental practices in human culture. However, the underlying neuronal mechanisms that may explain its powerful emotional and cognitive impact are unknown. In order to try to isolate the effect of silent repetitive speech, which is used in most commonly practiced Mantra meditative practices, on brain activity, we studied the neuronal correlates of simple repetitive speech in nonmeditators – that is, silent repetitive speech devoid of the wider context and spiritual orientations of commonly practiced meditation practices. Methods We compared, using blood oxygenated level-dependent (BOLD) functional magnetic resonance imaging (fMRI), a simple task of covertly repeating a single word to resting state activity, in 23 subjects, none of which practiced meditation before. Results We demonstrate that the repetitive speech was sufficient to induce a widespread reduction in BOLD signal compared to resting baseline. The reduction was centered mainly on the default mode network, associated with intrinsic, self-related processes. Importantly, contrary to most cognitive tasks, where cortical-reduced activation in one set of networks is typically complemented by positive BOLD activity of similar magnitude in other cortical networks, the repetitive speech practice resulted in unidirectional negative activity without significant concomitant positive BOLD. A subsequent behavioral study showed a significant reduction in intrinsic thought processes during the repetitive speech condition compared to rest. Conclusions Our results are compatible with a global gating model that can exert a widespread induction of negative BOLD in the absence of a corresponding positive activation. The triggering of a global inhibition by the minimally demanding repetitive speech may account for the long-established psychological calming effect associated with commonly practiced Mantra-related meditative practices. PMID

  3. A repeated injection of polyethyleneglycol-conjugated recombinant human butyrylcholinesterase elicits immune response in mice

    SciTech Connect

    Chilukuri, Nageswararao Sun Wei; Parikh, Kalpana; Naik, Ramachandra S.; Tang Lin; Doctor, Bhupendra P.; Saxena, Ashima

    2008-09-15

    Human serum butyrylcholinesterase (Hu BChE) serves as an efficacious bioscavenger of highly toxic organophosphorus (OP) compounds. Since there is a concern that the supply of native Hu BChE may be limited, monomeric and tetrameric forms of recombinant Hu BChE (rHu BChE) were evaluated as replacements and found that they lacked sufficient stability in vivo. However, their in vivo stability could be significantly prolonged by conjugation with polyethyleneglycol-20K (PEG) suggesting that monomeric and tetrameric PEG-rHu BChE could function as bioscavengers. Here, the immunogenicity of PEG-rHu BChE was evaluated in mice following two injections given four weeks apart. In addition to pharmacokinetic parameters, such as mean residence time, maximal concentration, time to reach the maximal concentration, elimination half-life and area under the plasma concentration-time curve extrapolated to infinity, the presence of circulating anti-rHu BChE antibodies was also determined. Although the pharmacokinetic parameters were significantly improved for the first injection of monomeric and tetrameric PEG-rHu BChEs, they were much lower for the second injection. Anti-rHu BChE antibodies were detected in the blood of mice following the first and second enzyme injections and their levels were approximately higher by 5-fold and 2-fold in mice injected with monomeric and tetrameric PEG-rHu BChEs as compared to mice injected with unconjugated enzymes. The findings that the rapid clearance of a repeat injection of PEG-rHu BChEs in mice which coincides with the presence of circulating anti-rHu BChE antibodies suggest that PEG conjugation prolonged the circulatory stability of rHu BChE but failed to eliminate its immunogenicity in mice.

  4. Spontaneous ultraweak photon emission imaging of oxidative metabolic processes in human skin: effect of molecular oxygen and antioxidant defense system.

    PubMed

    Rastogi, Anshu; Pospísil, Pavel

    2011-09-01

    All living organisms emit spontaneous ultraweak photon emission as a result of cellular metabolic processes. In this study, the involvement of reactive oxygen species (ROS) formed as the byproduct of oxidative metabolic processes in spontaneous ultraweak photon emission was studied in human hand skin. The effect of molecular oxygen and ROS scavengers on spontaneous ultraweak photon emission from human skin was monitored using a highly sensitive photomultiplier tube and charged coupled device camera. When spontaneous ultraweak photon emission was measured under anaerobic conditions, the photon emission was decreased, whereas under hyperaerobic condition the enhancement in photon emission was observed. Spontaneous ultraweak photon emission measured after topical application of glutathione, α-tocopherol, ascorbate, and coenzyme Q10 was observed to be decreased. These results reveal that ROS formed during the cellular metabolic processes in the epidermal cells play a significant role in the spontaneous ultraweak photon emission. It is proposed that spontaneous ultraweak photon emission can be used as a noninvasive tool for the temporal and spatial monitoring of the oxidative metabolic processes and intrinsic antioxidant system in human skin.

  5. Spontaneous ultraweak photon emission imaging of oxidative metabolic processes in human skin: effect of molecular oxygen and antioxidant defense system

    NASA Astrophysics Data System (ADS)

    Rastogi, Anshu; Pospíšil, Pavel

    2011-09-01

    All living organisms emit spontaneous ultraweak photon emission as a result of cellular metabolic processes. In this study, the involvement of reactive oxygen species (ROS) formed as the byproduct of oxidative metabolic processes in spontaneous ultraweak photon emission was studied in human hand skin. The effect of molecular oxygen and ROS scavengers on spontaneous ultraweak photon emission from human skin was monitored using a highly sensitive photomultiplier tube and charged coupled device camera. When spontaneous ultraweak photon emission was measured under anaerobic conditions, the photon emission was decreased, whereas under hyperaerobic condition the enhancement in photon emission was observed. Spontaneous ultraweak photon emission measured after topical application of glutathione, α-tocopherol, ascorbate, and coenzyme Q10 was observed to be decreased. These results reveal that ROS formed during the cellular metabolic processes in the epidermal cells play a significant role in the spontaneous ultraweak photon emission. It is proposed that spontaneous ultraweak photon emission can be used as a noninvasive tool for the temporal and spatial monitoring of the oxidative metabolic processes and intrinsic antioxidant system in human skin.

  6. Human embryonic stem cell-derived neuronal cells form spontaneously active neuronal networks in vitro.

    PubMed

    Heikkilä, Teemu J; Ylä-Outinen, Laura; Tanskanen, Jarno M A; Lappalainen, Riikka S; Skottman, Heli; Suuronen, Riitta; Mikkonen, Jarno E; Hyttinen, Jari A K; Narkilahti, Susanna

    2009-07-01

    The production of functional human embryonic stem cell (hESC)-derived neuronal cells is critical for the application of hESCs in treating neurodegenerative disorders. To study the potential functionality of hESC-derived neurons, we cultured and monitored the development of hESC-derived neuronal networks on microelectrode arrays. Immunocytochemical studies revealed that these networks were positive for the neuronal marker proteins beta-tubulin(III) and microtubule-associated protein 2 (MAP-2). The hESC-derived neuronal networks were spontaneously active and exhibited a multitude of electrical impulse firing patterns. Synchronous bursts of electrical activity similar to those reported for hippocampal neurons and rodent embryonic stem cell-derived neuronal networks were recorded from the differentiated cultures until up to 4 months. The dependence of the observed neuronal network activity on sodium ion channels was examined using tetrodotoxin (TTX). Antagonists for the glutamate receptors NMDA [D(-)-2-amino-5-phosphonopentanoic acid] and AMPA/kainate [6-cyano-7-nitroquinoxaline-2,3-dione], and for GABAA receptors [(-)-bicuculline methiodide] modulated the spontaneous electrical activity, indicating that pharmacologically susceptible neuronal networks with functional synapses had been generated. The findings indicate that hESC-derived neuronal cells can generate spontaneously active networks with synchronous communication in vitro, and are therefore suitable for use in developmental and drug screening studies, as well as for regenerative medicine.

  7. Eliciting expert opinion on the effectiveness and practicality of interventions in the farm and rural environment to reduce human exposure to Escherichia coli O157.

    PubMed

    Cross, P; Rigby, D; Edwards-Jones, G

    2012-04-01

    Few hard data are available on emergent diseases. However, the need to mitigate and manage emergent diseases has prompted the use of various expert consultation and opinion elicitation methods. We adapted best-worst scaling (BWS) to elicit experts' assessment of the relative practicality and effectiveness of measures to reduce human exposure to E. coli O157. Cattle vaccination was considered the most effective and hand-washing was considered the most practical measure. BWS proved a powerful tool for expert elicitation as it breaks down a cognitively burdensome process into simple, repeated, tasks. In addition, statistical analysis of the resulting data provides a scaled set of scores for the measures, rather than just a ranking. The use of two criteria (practicality and effectiveness) within the BWS process allows the identification of subsets of measures judged as potentially performing well on both criteria, and conversely those judged to be neither effective nor practical.

  8. Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide.

    PubMed Central

    Janson, J; Soeller, W C; Roche, P C; Nelson, R T; Torchia, A J; Kreutter, D K; Butler, P C

    1996-01-01

    The islet in non-insulin-dependent diabetes mellitus (NIDDM) is characterized by loss of beta cells and large local deposits of amyloid derived from the 37-amino acid protein, islet amyloid polypeptide (IAPP). We have hypothesized that IAPP amyloid forms intracellularly causing beta-cell destruction under conditions of high rates of expression. To test this we developed a homozygous transgenic mouse model with high rates of expression of human IAPP. Male transgenic mice spontaneously developed diabetes mellitus by 8 weeks of age, which was associated with selective beta-cell death and impaired insulin secretion. Small intra- and extracellular amorphous IAPP aggregates were present in islets of transgenic mice during the development of diabetes mellitus. However, IAPP derived amyloid deposits were found in only a minority of islets at approximately 20 weeks of age, notably after development of diabetes mellitus in male transgenic mice. Approximately 20% of female transgenic mice spontaneously developed diabetes mellitus at 30+ weeks of age, when beta-cell degeneration and both amorphous and amyloid deposits of IAPP were present. We conclude that overexpression of human IAPP causes beta-cell death, impaired insulin secretion, and diabetes mellitus. Large deposits of IAPP derived amyloid do not appear to be important in this cytotoxicity, but early, small amorphous intra- and extracellular aggregates of human IAPP were consistently present at the time of beta-cell death and therefore may be the most cytotoxic form of IAPP. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:8692984

  9. Spontaneous voice–face identity matching by rhesus monkeys for familiar conspecifics and humans

    PubMed Central

    Sliwa, Julia; Duhamel, Jean-René; Pascalis, Olivier; Wirth, Sylvia

    2011-01-01

    Recognition of a particular individual occurs when we reactivate links between current perceptual inputs and the previously formed representation of that person. This recognition can be achieved by identifying, separately or simultaneously, distinct elements such as the face, silhouette, or voice as belonging to one individual. In humans, those different cues are linked into one complex conceptual representation of individual identity. Here we tested whether rhesus macaques (Macaca mulatta) also have a cognitive representation of identity by evaluating whether they exhibit cross-modal individual recognition. Further, we assessed individual recognition of familiar conspecifics and familiar humans. In a free preferential looking time paradigm, we found that, for both species, monkeys spontaneously matched the faces of known individuals to their voices. This finding demonstrates that rhesus macaques possess a cross-modal cognitive representation of individuals that extends from conspecifics to humans, revealing the adaptive potential of identity recognition for individuals of socioecological relevance. PMID:21220340

  10. Molecular detection of adeno-associated virus in cases of spontaneous and intentional human abortion.

    PubMed

    Pereira, Christiane Curi; de Freitas, Luciana Bueno; de Vargas, Paulo Roberto Merçon; de Azevedo, Maria Luiza Borges; do Nascimento, Jussara Pereira; Spano, Liliana Cruz

    2010-10-01

    Pregnancy failure is a common event and often of unknown cause. Some viruses are thought to cause abortions including the adeno-associated viruses (AAV), viruses which are regarded as being without any definitive association to any human disease. This study investigated AAV infection in 81 human abortions, both spontaneous and intentional that occurred up to the 23rd week of gestation. Nucleic acid of AAV-2, 3, and 5 types from 118 decidual and chorionic tissues, collected from the patients in this study, was amplified by nested-PCR. In situ hybridization (ISH) was developed with a digoxigenin-labeled AAV probe in paraffin embedded tissues from the AAV positive cases. AAV was observed in 28.4% (23/81) of the cases, of which, 78.3% (18/23) were in the decidua and 21.7% (5/23) in the extravillous trophoblast, the chorionic plate, or chorionic villi fragments. AAV-2, the only type detected, occurred in 32.3% (22/68) and in 7.7% (1/13) of the spontaneous and intentional abortions, respectively. ISH revealed AAV in the decidua, chorionic tissue or chorionic plate and extravillous trophoblast. The detection of only AAV-2 type indicates that it is the most frequent in the population studied and/or shows tissue tropism. The presence of AAV in decidual or trophoblastic cells in cases of abortion, as observed by ISH, implies that the virus could jeopardize the pregnancy. The significant predominance in spontaneous cases suggests possibly a causal association between AAV and abortion. PMID:20827766

  11. Frequency selectivity of the human cochlea: Suppression tuning of spontaneous otoacoustic emissions.

    PubMed

    Manley, Geoffrey A; van Dijk, Pim

    2016-06-01

    Frequency selectivity is a key functional property of the inner ear and since hearing research began, the frequency resolution of the human ear has been a central question. In contrast to animal studies, which permit invasive recording of neural activity, human studies must rely on indirect methods to determine hearing selectivity. Psychophysical studies, which used masking of a tone by other sounds, indicate a modest frequency selectivity in humans. By contrast, estimates using the phase delays of stimulus-frequency otoacoustic emissions (SFOAE) predict a remarkably high selectivity, unique among mammals. An alternative measure of cochlear frequency selectivity are suppression tuning curves of spontaneous otoacoustic emissions (SOAE). Several animal studies show that these measures are in excellent agreement with neural frequency selectivity. Here we contribute a large data set from normal-hearing young humans on suppression tuning curves (STC) of spontaneous otoacoustic emissions (SOAE). The frequency selectivities of human STC measured near threshold levels agree with the earlier, much lower, psychophysical estimates. They differ, however, from the typical patterns seen in animal auditory nerve data in that the selectivity is remarkably independent of frequency. In addition, SOAE are suppressed by higher-level tones in narrow frequency bands clearly above the main suppression frequencies. These narrow suppression bands suggest interactions between the suppressor tone and a cochlear standing wave corresponding to the SOAE frequency being suppressed. The data show that the relationship between pre-neural mechanical processing in the cochlea and neural coding at the hair-cell/auditory nerve synapse needs to be reconsidered. PMID:27139323

  12. Frequency selectivity of the human cochlea: Suppression tuning of spontaneous otoacoustic emissions.

    PubMed

    Manley, Geoffrey A; van Dijk, Pim

    2016-06-01

    Frequency selectivity is a key functional property of the inner ear and since hearing research began, the frequency resolution of the human ear has been a central question. In contrast to animal studies, which permit invasive recording of neural activity, human studies must rely on indirect methods to determine hearing selectivity. Psychophysical studies, which used masking of a tone by other sounds, indicate a modest frequency selectivity in humans. By contrast, estimates using the phase delays of stimulus-frequency otoacoustic emissions (SFOAE) predict a remarkably high selectivity, unique among mammals. An alternative measure of cochlear frequency selectivity are suppression tuning curves of spontaneous otoacoustic emissions (SOAE). Several animal studies show that these measures are in excellent agreement with neural frequency selectivity. Here we contribute a large data set from normal-hearing young humans on suppression tuning curves (STC) of spontaneous otoacoustic emissions (SOAE). The frequency selectivities of human STC measured near threshold levels agree with the earlier, much lower, psychophysical estimates. They differ, however, from the typical patterns seen in animal auditory nerve data in that the selectivity is remarkably independent of frequency. In addition, SOAE are suppressed by higher-level tones in narrow frequency bands clearly above the main suppression frequencies. These narrow suppression bands suggest interactions between the suppressor tone and a cochlear standing wave corresponding to the SOAE frequency being suppressed. The data show that the relationship between pre-neural mechanical processing in the cochlea and neural coding at the hair-cell/auditory nerve synapse needs to be reconsidered.

  13. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models

    PubMed Central

    Liu, Huiping; Patel, Manishkumar R.; Prescher, Jennifer A.; Patsialou, Antonia; Qian, Dalong; Lin, Jiahui; Wen, Susanna; Chang, Ya-Fang; Bachmann, Michael H.; Shimono, Yohei; Dalerba, Piero; Adorno, Maddalena; Lobo, Neethan; Bueno, Janet; Dirbas, Frederick M.; Goswami, Sumanta; Somlo, George; Condeelis, John; Contag, Christopher H.; Gambhir, Sanjiv Sam; Clarke, Michael F.

    2010-01-01

    To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled with optical reporter fusion genes. These models recapitulate human cancer features not captured with previous models, including spontaneous metastasis in particular, and provide a useful platform for studies of breast tumor initiation and progression. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. These advances in BCSC imaging revealed that CD44+ cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy. PMID:20921380

  14. Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in spontaneously hypertensive rats.

    PubMed

    Sabaawy, H E; Zhang, F; Nguyen, X; ElHosseiny, A; Nasjletti, A; Schwartzman, M; Dennery, P; Kappas, A; Abraham, N G

    2001-08-01

    Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, with release of free iron and carbon monoxide. Both heme and carbon monoxide have been implicated in the regulation of vascular tone. A retroviral vector containing human HO-1 cDNA (LSN-HHO-1) was constructed and subjected to purification and concentration of the viral particles to achieve 5x10(9) to 1x10(10) colony-forming units per milliliter. The ability of concentrated infectious viral particles to express human HO-1 (HHO-1) in vivo was tested. A single intracardiac injection of the concentrated infectious viral particles (expressing HHO-1) to 5-day-old spontaneously hypertensive rats resulted in functional expression of the HHO-1 gene and attenuation of the development of hypertension. Rats expressing HHO-1 showed a significant decrease in urinary excretion of a vasoconstrictor arachidonic acid metabolite and a reduction in myogenic responses to increased intraluminal pressure in isolated arterioles. Unexpectedly, HHO-1 chimeric rats showed a simultaneous significant proportionate increase in somatic growth. Thus, delivery of HHO-1 gene by retroviral vector attenuates the development of hypertension and promotes body growth in spontaneously hypertensive rats.

  15. Integrin-Mediated Adhesion and Proliferation of Human MCs Elicited by A Hydroxyproline-Lacking, Collagen-like Peptide

    PubMed Central

    Krishna, Ohm D.; Jha, Amit K.; Jia, Xinqiao; Kiick, Kristi L.

    2011-01-01

    In this study, we evaluated the competence of a rationally designed collagen-like peptide (CLP-Cys) sequence - containing the minimal essential Glycine-Glutamic acid-Arginine (GER) triplet but lacking the hydroxyproline residue - for supporting human mesenchymal stem cell (hMSC) adhesion, spreading and proliferation. Cellular responses to the CLP-Cys sequence were analyzed by conjugating the peptide to two different substrates – a hard, planar glass surface and a soft hyaluronic acid (HA) particle-based hydrogel. Integrin-mediated cell spreading and adhesion were observed for hMSCs cultivated on the CLP-Cys functionalized surfaces, whereas on control surfaces lacking the peptide motif, cells either did not adhere or maintained a round morphology. On the glass surface, CLP-Cys-mediated spreading led to the formation of extended and well developed stress fibers composed of F-actin bundles and focal adhesion complexes while on the soft gel surface, less cytoskeletal reorganization was observed. The hMSCs proliferated significantly on the surfaces presenting CLP-Cys, compared to the control surfaces lacking CLP-Cys. Competitive binding assay employing soluble CLP-Cys revealed a dose-dependent inhibition of hMSC adhesion to the CLP-Cys-presenting surfaces. Blocking the α2β1 receptor on hMSC also resulted in a reduction of cell adhesion on both types of CLP-Cys surfaces, confirming the affinity of CLP-Cys to α2β1 receptors. These results established the competence of the hydroxyproline-free CLP-Cys for eliciting integrin-mediated cellular responses including adhesion, spreading and proliferation. Thus, CLP-Cys-modified HA hydrogels are attractive candidates as bioactive scaffolds for tissue engineering applications. PMID:21658756

  16. A Melodic Contour Repeatedly Experienced by Human Near-Term Fetuses Elicits a Profound Cardiac Reaction One Month after Birth

    PubMed Central

    Granier-Deferre, Carolyn; Bassereau, Sophie; Ribeiro, Aurélie; Jacquet, Anne-Yvonne; DeCasper, Anthony J.

    2011-01-01

    Background Human hearing develops progressively during the last trimester of gestation. Near-term fetuses can discriminate acoustic features, such as frequencies and spectra, and process complex auditory streams. Fetal and neonatal studies show that they can remember frequently recurring sounds. However, existing data can only show retention intervals up to several days after birth. Methodology/Principal Findings Here we show that auditory memories can last at least six weeks. Experimental fetuses were given precisely controlled exposure to a descending piano melody twice daily during the 35th, 36th, and 37th weeks of gestation. Six weeks later we assessed the cardiac responses of 25 exposed infants and 25 naive control infants, while in quiet sleep, to the descending melody and to an ascending control piano melody. The melodies had precisely inverse contours, but similar spectra, identical duration, tempo and rhythm, thus, almost identical amplitude envelopes. All infants displayed a significant heart rate change. In exposed infants, the descending melody evoked a cardiac deceleration that was twice larger than the decelerations elicited by the ascending melody and by both melodies in control infants. Conclusions/Significance Thus, 3-weeks of prenatal exposure to a specific melodic contour affects infants ‘auditory processing’ or perception, i.e., impacts the autonomic nervous system at least six weeks later, when infants are 1-month old. Our results extend the retention interval over which a prenatally acquired memory of a specific sound stream can be observed from 3–4 days to six weeks. The long-term memory for the descending melody is interpreted in terms of enduring neurophysiological tuning and its significance for the developmental psychobiology of attention and perception, including early speech perception, is discussed. PMID:21383836

  17. Reduced graphene oxide-coated hydroxyapatite composites stimulate spontaneous osteogenic differentiation of human mesenchymal stem cells

    NASA Astrophysics Data System (ADS)

    Lee, Jong Ho; Shin, Yong Cheol; Jin, Oh Seong; Kang, Seok Hee; Hwang, Yu-Shik; Park, Jong-Chul; Hong, Suck Won; Han, Dong-Wook

    2015-07-01

    Human mesenchymal stem cells (hMSCs) have great potential as cell sources for bone tissue engineering and regeneration, but the control and induction of their specific differentiation into bone cells remain challenging. Graphene-based nanomaterials are considered attractive candidates for biomedical applications such as scaffolds in tissue engineering, substrates for SC differentiation and components of implantable devices, due to their biocompatible and bioactive properties. Despite the potential biomedical applications of graphene and its derivatives, only limited information is available regarding their osteogenic activity. This study concentrates upon the effects of reduced graphene oxide (rGO)-coated hydroxyapatite (HAp) composites on osteogenic differentiation of hMSCs. The average particle sizes of HAp and rGO were 1270 +/- 476 nm and 438 +/- 180 nm, respectively. When coated on HAp particulates, rGO synergistically enhanced spontaneous osteogenic differentiation of hMSCs, without hampering their proliferation. This result was confirmed by determining alkaline phosphatase activity and mineralization of calcium and phosphate as early and late stage markers of osteogenic differentiation. It is suggested that rGO-coated HAp composites can be effectively utilized as dental and orthopedic bone fillers since these graphene-based particulate materials have potent effects on stimulating the spontaneous differentiation of MSCs and show superior bioactivity and osteoinductive potential.Human mesenchymal stem cells (hMSCs) have great potential as cell sources for bone tissue engineering and regeneration, but the control and induction of their specific differentiation into bone cells remain challenging. Graphene-based nanomaterials are considered attractive candidates for biomedical applications such as scaffolds in tissue engineering, substrates for SC differentiation and components of implantable devices, due to their biocompatible and bioactive properties. Despite

  18. Eliciting Expertise.

    ERIC Educational Resources Information Center

    Mills, William deB.

    1989-01-01

    Recommends using expert systems on personal computers in the classroom to teach international relations. Claims these systems can reach conclusions as reliable as those of a human expert. Explains that the system compels students to draw conclusions based on clarity of thought because they rely on a body of logically consistent rules. (NL)

  19. Molecular homology and difference between spontaneous canine mammary cancer and human breast cancer

    PubMed Central

    Liu, Deli; Xiong, Huan; Ellis, Angela E.; Northrup, Nicole C.; Rodriguez, Carlos O.; O'Regan, Ruth M.; Dalton, Stephen; Zhao, Shaying

    2014-01-01

    Spontaneously occurring canine mammary cancer (MC) represents an excellent model of human breast cancer but is greatly understudied. To better utilize this valuable resource, we performed whole genome sequencing, whole exome sequencing, RNA-seq and/or high density arrays on 12 canine MC cases, including 7 simple carcinomas and four complex carcinomas. Canine simple carcinomas, which histologically match human breast carcinomas, harbor extensive genomic aberrations, many of which faithfully recapitulate key features of human breast cancer. Canine complex carcinomas, which are characterized by proliferation of both luminal and myoepithelial cells and are rare in human breast cancer, appear to lack genomic abnormalities. Instead, these tumors have about 35 chromatin-modification genes downregulated, and are abnormally enriched with active histone modification H4-acetylation while aberrantly depleted with repressive histone modification H3K9me3. Our findings indicate the likelihood that canine simple carcinomas arise from genomic aberrations whereas complex carcinomas originate from epigenomic alterations, reinforcing their unique value. Canine complex carcinomas offer an ideal system to study myoepithelial cells, the second major cell lineage of the mammary gland. Canine simple carcinomas, which faithfully represent human breast carcinomas at the molecular level, provide indispensable models for basic and translational breast cancer research. PMID:25082814

  20. Molecular homology and difference between spontaneous canine mammary cancer and human breast cancer.

    PubMed

    Liu, Deli; Xiong, Huan; Ellis, Angela E; Northrup, Nicole C; Rodriguez, Carlos O; O'Regan, Ruth M; Dalton, Stephen; Zhao, Shaying

    2014-09-15

    Spontaneously occurring canine mammary cancer represents an excellent model of human breast cancer, but is greatly understudied. To better use this valuable resource, we performed whole-genome sequencing, whole-exome sequencing, RNA-seq, and/or high-density arrays on twelve canine mammary cancer cases, including seven simple carcinomas and four complex carcinomas. Canine simple carcinomas, which histologically match human breast carcinomas, harbor extensive genomic aberrations, many of which faithfully recapitulate key features of human breast cancer. Canine complex carcinomas, which are characterized by proliferation of both luminal and myoepithelial cells and are rare in human breast cancer, seem to lack genomic abnormalities. Instead, these tumors have about 35 chromatin-modification genes downregulated and are abnormally enriched with active histone modification H4-acetylation, whereas aberrantly depleted with repressive histone modification H3K9me3. Our findings indicate the likelihood that canine simple carcinomas arise from genomic aberrations, whereas complex carcinomas originate from epigenomic alterations, reinforcing their unique value. Canine complex carcinomas offer an ideal system to study myoepithelial cells, the second major cell lineage of the mammary gland. Canine simple carcinomas, which faithfully represent human breast carcinomas at the molecular level, provide indispensable models for basic and translational breast cancer research. PMID:25082814

  1. Reconstruction of human brain spontaneous activity based on frequency-pattern analysis of magnetoencephalography data

    PubMed Central

    Llinás, Rodolfo R.; Ustinin, Mikhail N.; Rykunov, Stanislav D.; Boyko, Anna I.; Sychev, Vyacheslav V.; Walton, Kerry D.; Rabello, Guilherme M.; Garcia, John

    2015-01-01

    A new method for the analysis and localization of brain activity has been developed, based on multichannel magnetic field recordings, over minutes, superimposed on the MRI of the individual. Here, a high resolution Fourier Transform is obtained over the entire recording period, leading to a detailed multi-frequency spectrum. Further analysis implements a total decomposition of the frequency components into functionally invariant entities, each having an invariant field pattern localizable in recording space. The method, addressed as functional tomography, makes it possible to find the distribution of magnetic field sources in space. Here, the method is applied to the analysis of simulated data, to oscillating signals activating a physical current dipoles phantom, and to recordings of spontaneous brain activity in 10 healthy adults. In the analysis of simulated data, 61 dipoles are localized with 0.7 mm precision. Concerning the physical phantom the method is able to localize three simultaneously activated current dipoles with 1 mm precision. Spatial resolution 3 mm was attained when localizing spontaneous alpha rhythm activity in 10 healthy adults, where the alpha peak was specified for each subject individually. Co-registration of the functional tomograms with each subject's head MRI localized alpha range activity to the occipital and/or posterior parietal brain region. This is the first application of this new functional tomography to human brain activity. The method successfully provides an overall view of brain electrical activity, a detailed spectral description and, combined with MRI, the localization of sources in anatomical brain space. PMID:26528119

  2. Triclosan causes spontaneous abortion accompanied by decline of estrogen sulfotransferase activity in humans and mice.

    PubMed

    Wang, Xiaoli; Chen, Xiaojiao; Feng, Xuejiao; Chang, Fei; Chen, Minjian; Xia, Yankai; Chen, Ling

    2015-12-15

    Triclosan (TCS), an antibacterial agent, is identified in serum and urine of humans. Here, we show that the level of urinary TCS in 28.3% patients who had spontaneous abortion in mid-gestation were increased by 11.3-fold (high-TCS) compared with normal pregnancies. Oral administration of TCS (10 mg/kg/day) in mice (TCS mice) caused an equivalent urinary TCS level as those in the high-TCS abortion patients. The TCS-exposure from gestation day (GD) 5.5 caused dose-dependently fetal death during GD12.5-16.5 with decline of live fetal weight. GD15.5 TCS mice appeared placental thrombus and tissue necrosis with enhancement of platelet aggregation. The levels of placenta and plasma estrogen sulfotransferase (EST) mRNA and protein in TCS mice or high-TCS abortion patients were not altered, but their EST activities were significantly reduced compared to controls. Although the levels of serum estrogen (E2) in TCS mice and high-TCS abortion patients had no difference from controls, their ratio of sulfo-conjugated E2 and unconjugated E2 was reduced. The estrogen receptor antagonist ICI-182,780 prevented the enhanced platelet aggregation and placental thrombosis and attenuated the fetal death in TCS mice. The findings indicate that TCS-exposure might cause spontaneous abortion probably through inhibition of EST activity to produce placental thrombosis.

  3. Policy relevant Results from an Expert Elicitation on the Human Health Risks of Decabromodiphenyl ether (decaBDE) and Hexabromocyclododecane (HBCD)

    PubMed Central

    2012-01-01

    Aim Apply a recently developed expert elicitation procedure to evaluate the state of the current knowledge of the two brominated flame retardants (BFRs) most commonly used today; decabromo-diphenyl ether (decaBDE) and hexabromocyclododecane (HBCD) and their potential impact on human health in order to support policy considerations. This expert elicitation was organized by the HENVINET (Health and Environment Network) Consortium. Method The HENVINET expert elicitation procedure that was used in the evaluations of decaBDE and HBCD is a rapid assessment tool aimed at highlighting areas of agreement and areas of disagreement on knowledge-related key issues for environment and health policy decision making. Results The outcome of the expert consultation on BFRs was concrete expert advice for policy makers with specific priorities for further action made clear for both stakeholders and policy makers. The experts were not in agreement whether or not the knowledge currently available on decaBDE or HBCD is sufficient to justify policy actions, but most experts considered that enough data already exists to support a ban or restriction on the use of these compounds. All experts agreed on the necessity of more research on the compounds. Priority issues for further research were, among others: • more studies on the extent of human exposure to the compounds. • more studies on the fate and concentration in the human body of the compounds. PMID:22759507

  4. ATP in human skin elicits a dose-related pain response which is potentiated under conditions of hyperalgesia.

    PubMed

    Hamilton, S G; Warburton, J; Bhattacharjee, A; Ward, J; McMahon, S B

    2000-06-01

    Despite the considerable interest in the possibility that ATP may function as a peripheral pain mediator, there has been little quantitative study of the pain-producing effects of ATP in humans. Here we have used iontophoresis to deliver ATP to the forearm skin of volunteers who rated the magnitude of the evoked pain on a visual analogue scale. ATP consistently produced a modest burning pain, which began within 20 s of starting iontophoresis and was maintained for several minutes. Persistent iontophoresis of ATP led to desensitization within 12 min but recovery from this was almost complete 1 h later. Different doses of ATP were delivered using different iontophoretic driving currents. Iontophoresis of ATP produced a higher pain rating than saline, indicating that the pain was specifically caused by ATP. The average pain rating for ATP, but not saline, increased with increasing current. Using an 0.8 mA current, subjects reported pain averaging 27.7 +/- 2.8 (maximum possible = 100). Iontophoresis of ATP caused an increase in blood flow, as assessed using a laser Doppler flow meter. The increase in blood flow was significantly greater using ATP than saline in both the iontophoresed skin (P < 0.01) and in the surrounding skin, 3 mm outside the iontophoresed area (P < 0.05). The pain produced by ATP was dependent on capsaicin-sensitive sensory neurons, since in skin treated repeatedly with topical capsaicin pain was reduced to less than 25% of that elicited on normal skin (2.1 +/- 0.4 compared with 9.3 +/- 1.5 on normal skin). Conversely, the pain-producing effects of ATP were greatly potentiated in several models of hyperalgesia. Thus, with acute capsaicin treatment when subjects exhibited touch-evoked hyperalgesia but no ongoing pain, there was a threefold increase in the average pain rating during ATP iontophoresis (22.7 +/- 3.1) compared with pre-capsaicin treatment (7.8 +/- 2.6). Moreover, ATP iontophoresed into skin 24 h after solar simulated radiation (2 x

  5. Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term

    PubMed Central

    Mittal, Pooja; Romero, Roberto; Tarca, Adi L.; Gonzalez, Juan; Draghici, Sorin; Xu, Yi; Dong, Zhong; Nhan-Chang, Chia-Ling; Chaiworapongsa, Tinnakorn; Lye, Stephen; Kusanovic, Juan Pedro; Lipovich, Leonard; Mazaki-Tovi, Shali; Hassan, Sonia S.; Mesiano, Sam; Kim, Chong Jai

    2011-01-01

    Aims To characterize the transcriptome of human myometrium during spontaneous labor at term. Methods Myometrium was obtained from women with (n=19) and without labor (n=20). Illumina® HumanHT-12 microarrays were utilized. Moderated t-tests and False Discovery Rate adjustment of p-values were applied. qRT-PCR was performed for a select set of differentially expressed genes in a separate set of samples. ELISA and Western Blot were utilized to confirm differential protein production in a third sample set. Results 1) 471 genes were differentially expressed; 2) Gene Ontology analysis indicated enrichment of 103 biological processes and 18 molecular functions including: a) inflammatory response; b) cytokine activity; and c) chemokine activity; 3) systems biology pathway analysis using Signaling Pathway Impact Analysis indicated 6 significant pathways: a) cytokine-cytokine receptor interaction; b) Jak-Stat signaling; and c) complement and coagulation cascades; d) NOD-like receptor signaling pathway; e) Systemic Lupus Erythematosus; and f) Chemokine signaling pathway; 3) qRT-PCR confirmed over-expression of prostaglandin-endoperoxide synthase-2 (PTGS2/COX2), heparin binding EGF-like growth factor (HBEGF), chemokine C-C motif ligand 2 (CCL2/MCP1), leukocyte immunoglobulin-like receptor, subfamily A member 5 (LILRA5/LIR9), IL-8, IL-6, chemokine C-X-C motif ligand 6 (CXCL6/GCP2), nuclear factor of kappa light chain gene enhancer in B-cells inhibitor zeta (NFKBIZ), suppressor of cytokine signaling 3 (SOCS3) and decreased expression of FK506 binding-protein 5 (FKBP5) and aldehyde dehydrogenase (ALDH2) in labor; 4) IL-6, CXCL6, CCL2 and SOCS3 protein expression was significantly higher in the term labor group compared to the term not in labor group. Conclusions Myometrium of women in spontaneous labor at term is characterized by a stereotypic gene expression pattern consistent with over-expression of the inflammatory response and leukocyte chemotaxis. Differential gene

  6. Chemokine CCL28 induces apoptosis of decidual stromal cells via binding CCR3/CCR10 in human spontaneous abortion.

    PubMed

    Sun, Chan; Zhang, Yuan-Yuan; Tang, Chuan-Ling; Wang, Song-Cun; Piao, Hai-Lan; Tao, Yu; Zhu, Rui; Du, Mei-Rong; Li, Da-Jin

    2013-10-01

    Spontaneous abortion is the most common complication of pregnancy. Immune activation and the subsequent inflammation-induced tissue injury are often observed at the maternal-fetal interface as the final pathological assault in recurrent spontaneous abortion. However, the precise mechanisms responsible for spontaneous abortion involving inflammation are not fully understood. Chemokine CCL28 and its receptors CCR3 and CCR10 are important regulators in inflammatory process. Here, we examined the expression of CCL28 and its receptors in decidual stromal cells (DSCs) by immunochemistry and flow cytometry (FCM), and compared their expression level in DSCs from normal pregnancy versus spontaneous abortion, and their relationship to inflammatory cytokines production by DSCs. We further analyzed regulation of the pro-inflammatory cytokines on CCL28 expression in DSCs by real-time polymerase chain reaction, In-cell Western and FCM. The effects of CCL28-CCR3/CCR10 interaction on DSC apoptosis was investigated by Annexin V staining and FCM analysis or DAPI staining and nuclear morphology. Higher levels of the inflammatory cytokines interleukin (IL)-1β, IL-17A and tumor necrosis factor-α, and increased CCR3/CCR10 expression were observed in DSCs from spontaneous abortion compared with normal pregnancy. Treatment with inflammatory cytokines differently affected CCL28 and CCR3/CCR10 expression in DSCs. Human recombinant CCL28 promoted DSC apoptosis, which was eliminated by pretreatment with neutralizing antibodies against CCR3/CCR10 and CCL28. However, CCL28 did not affect DSC growth. These results suggest that the inflammation-promoted up-regulation of CCL28 and its receptors interaction in DSCs is involved in human spontaneous abortion via inducing DSC apoptosis.

  7. Sex hormone influence on human infants' sound characteristics: melody in spontaneous crying.

    PubMed

    Wermke, Kathleen; Hain, Johannes; Oehler, Klaus; Wermke, Peter; Hesse, Volker

    2014-05-01

    The specific impact of sex hormones on brain development and acoustic communication is known from animal models. Sex steroid hormones secreted during early development play an essential role in hemispheric organization and the functional lateralization of the brain, e.g. language. In animals, these hormones are well-known regulators of vocal motor behaviour. Here, the association between melody properties of infants' sounds and serum concentrations of sex steroids was investigated. Spontaneous crying was sampled in 18 healthy infants, averaging two samples taken at four and eight weeks, respectively. Blood samples were taken within a day of the crying samples. The fundamental frequency contour (melody) was analysed quantitatively and the infants' frequency modulation skills expressed by a melody complexity index (MCI). These skills provide prosodic primitives for later language. A hierarchical, multiple regression approach revealed a significant, robust relationship between the individual MCIs and the unbound, bioactive fraction of oestradiol at four weeks as well as with the four-to-eight-week difference in androstenedione. No robust relationship was found between the MCI and testosterone. Our findings suggest that oestradiol may have effects on the development and function of the auditory-vocal system in human infants that are as powerful as those in vocal-learning animals.

  8. Sex hormone influence on human infants' sound characteristics: melody in spontaneous crying

    PubMed Central

    Wermke, Kathleen; Hain, Johannes; Oehler, Klaus; Wermke, Peter; Hesse, Volker

    2014-01-01

    The specific impact of sex hormones on brain development and acoustic communication is known from animal models. Sex steroid hormones secreted during early development play an essential role in hemispheric organization and the functional lateralization of the brain, e.g. language. In animals, these hormones are well-known regulators of vocal motor behaviour. Here, the association between melody properties of infants' sounds and serum concentrations of sex steroids was investigated. Spontaneous crying was sampled in 18 healthy infants, averaging two samples taken at four and eight weeks, respectively. Blood samples were taken within a day of the crying samples. The fundamental frequency contour (melody) was analysed quantitatively and the infants' frequency modulation skills expressed by a melody complexity index (MCI). These skills provide prosodic primitives for later language. A hierarchical, multiple regression approach revealed a significant, robust relationship between the individual MCIs and the unbound, bioactive fraction of oestradiol at four weeks as well as with the four-to-eight-week difference in androstenedione. No robust relationship was found between the MCI and testosterone. Our findings suggest that oestradiol may have effects on the development and function of the auditory–vocal system in human infants that are as powerful as those in vocal-learning animals. PMID:24806423

  9. Eicosanomic profiling reveals dominance of the epoxygenase pathway in human amniotic fluid at term in spontaneous labor

    PubMed Central

    Maddipati, Krishna Rao; Romero, Roberto; Chaiworapongsa, Tinnakorn; Zhou, Sen-Lin; Xu, Zhonghui; Tarca, Adi L.; Kusanovic, Juan Pedro; Munoz, Hernan; Honn, Kenneth V.

    2014-01-01

    Lipid mediators play an important role in reproductive biology, especially, in parturition. Enhanced biosynthesis of eicosanoids, such as prostaglandin E2 (PGE2) and PGF2α, precedes the onset of labor as a result of increased expression of inducible cyclooxygenase 2 (COX-2) in placental tissues. Metabolism of arachidonic acid results in bioactive lipid mediators beyond prostaglandins that could significantly influence myometrial activity. Therefore, an unbiased lipidomic approach was used to profile the arachidonic acid metabolome of amniotic fluid. In this study, liquid chromatography–mass spectrometry was used for the first time to quantitate these metabolites in human amniotic fluid by comparing patients at midtrimester, at term but not in labor, and at term and in spontaneous labor. In addition to exposing novel aspects of COX pathway metabolism, this lipidomic study revealed a dramatic increase in epoxygenase- and lipoxygenase-pathway-derived lipid mediators in spontaneous labor with remarkable product selectivity. Despite their recognition as anti-inflammatory lipid mediators and regulators of ion channels, little is known about the epoxygenase pathway in labor. Epoxygenase pathway metabolites are established regulators of vascular homeostasis in cardiovascular and renal physiology. Their presence as the dominant lipid mediators in spontaneous labor at term portends a yet undiscovered physiological function in parturition.—Maddipati, K. R., Romero, R., Chaiworapongsa, T., Zhou, S.-L., Xu, Z., Tarca, A. L., Kusanovic, J. P., Munoz, H., Honn, K. V. Eicosanomic profiling reveals dominance of the epoxygenase pathway in human amniotic fluid at term in spontaneous labor. PMID:25059230

  10. Spontaneous hypothermia in human sepsis is a transient, self-limiting, and nonterminal response.

    PubMed

    Fonseca, Monique T; Rodrigues, Abner C; Cezar, Luana C; Fujita, Andre; Soriano, Francisco G; Steiner, Alexandre A

    2016-06-15

    Hypothermia in sepsis is generally perceived as something dysregulated and progressive although there has been no assessment on the natural course of this phenomenon in humans. This was the first study on the dynamics of hypothermia in septic patients not subjected to active rewarming, and the results were surprising. A sample of 50 subjects presenting with spontaneous hypothermia during sepsis was drawn from the 2005-2012 database of an academic hospital. Hypothermia was defined as body temperature below 36.0°C for longer than 2 h, with at least one reading of 35.5°C or less. The patients presented with 138 episodes of hypothermia, 21 at the time of the sepsis diagnosis and 117 with a later onset. However, hypothermia was uncommon in the final 12 h of life of the patients that succumbed. The majority (97.1%) of the hypothermic episodes were transient and self-limited; the median recovery time was 6 h; body temperature rarely fell below 34.0°C. Bidirectional oscillations in body temperature were evident in the course of hypothermia. Nearly half of the hypothermic episodes had onset in the absence of shock or respiratory distress, and the incidence of hypothermia was not increased during either of these conditions. Usage of antipyretic drugs, sedatives, neuroleptics, or other medications did not predict the onset of hypothermia. In conclusion, hypothermia appears to be a predominantly transient, self-limiting, and nonterminal phenomenon that is inherent to human sepsis. These characteristics resemble those of the regulated hypothermia shown to replace fever in animal models of severe systemic inflammation.

  11. Spontaneous hypothermia in human sepsis is a transient, self-limiting, and nonterminal response.

    PubMed

    Fonseca, Monique T; Rodrigues, Abner C; Cezar, Luana C; Fujita, Andre; Soriano, Francisco G; Steiner, Alexandre A

    2016-06-15

    Hypothermia in sepsis is generally perceived as something dysregulated and progressive although there has been no assessment on the natural course of this phenomenon in humans. This was the first study on the dynamics of hypothermia in septic patients not subjected to active rewarming, and the results were surprising. A sample of 50 subjects presenting with spontaneous hypothermia during sepsis was drawn from the 2005-2012 database of an academic hospital. Hypothermia was defined as body temperature below 36.0°C for longer than 2 h, with at least one reading of 35.5°C or less. The patients presented with 138 episodes of hypothermia, 21 at the time of the sepsis diagnosis and 117 with a later onset. However, hypothermia was uncommon in the final 12 h of life of the patients that succumbed. The majority (97.1%) of the hypothermic episodes were transient and self-limited; the median recovery time was 6 h; body temperature rarely fell below 34.0°C. Bidirectional oscillations in body temperature were evident in the course of hypothermia. Nearly half of the hypothermic episodes had onset in the absence of shock or respiratory distress, and the incidence of hypothermia was not increased during either of these conditions. Usage of antipyretic drugs, sedatives, neuroleptics, or other medications did not predict the onset of hypothermia. In conclusion, hypothermia appears to be a predominantly transient, self-limiting, and nonterminal phenomenon that is inherent to human sepsis. These characteristics resemble those of the regulated hypothermia shown to replace fever in animal models of severe systemic inflammation. PMID:26989218

  12. Human temporal-parietal junction spontaneously tracks others' beliefs: A functional near-infrared spectroscopy study.

    PubMed

    Hyde, Daniel C; Aparicio Betancourt, Mariana; Simon, Charline E

    2015-12-01

    Humans have the unique capacity to actively reflect on the thoughts, beliefs, and knowledge of others, but do we also track mental states spontaneously when observing other people? We asked this question by monitoring brain activity in belief-sensitive cortex using functional near-infrared spectroscopy (fNIRS) during free-viewing of social videos. More specifically, we identified a portion of the right temporal-parietal junction (rTPJ) selective for mental state processing using an established, explicit theory of mind task, and then analyzed the brain response in that region of interest (ROI) during free-viewing of video clips involving people producing goal-directed actions. We found a significant increase in oxygenated hemoglobin concentration in our rTPJ ROI during free-viewing for all of our test videos. Activity in this region was further modulated by the extent to which the knowledge state, or beliefs, of the protagonist regarding the location of an object contrasted with the reality of where the object was hidden. Open-ended questioning suggested our participants were not explicitly focusing on belief states of the characters during free-viewing. Further analyses ruled out lower-level details of the video clips or general attentional differences between conditions as likely explanations for the results. As such, these results call into question the traditional characterization of theory of mind as a resource intensive, deliberate process, and, instead, support an emerging view of theory of mind as a foundation for, rather than the pinnacle of, human social cognition.

  13. Decoding of Baby Calls: Can Adult Humans Identify the Eliciting Situation from Emotional Vocalizations of Preverbal Infants?

    PubMed

    Lindová, Jitka; Špinka, Marek; Nováková, Lenka

    2015-01-01

    Preverbal infants often vocalize in emotionally loaded situations, yet the communicative potential of these vocalizations is not well understood. The aim of our study was to assess how accurately adult listeners extract information about the eliciting situation from infant preverbal vocalizations. Vocalizations of 19 infants aged 5-10 months were recorded in 3 negative (Pain, Isolation, Demand for Food) and 3 positive (Play, Reunion, After Feeding) situations. The recordings were later rated by 333 adult listeners on the scales of emotional valence and intensity. Subsequently, the listeners assigned the eliciting situations in a forced choice task. Listeners were almost perfectly able to discriminate whether a recording came from a negative or a positive situation. Their discrimination may have been based on perceived valence as they consistently assigned higher valence when listening to positive, and lower valence when listening to negative, recordings. Ability to identify the particular situation within the negative or positive realm was substantially weaker, with only three of the six situations being discriminated above chance. The best discriminated situation, Play, was associated with high perceived intensity. The weak qualitative discrimination of negative situations seemed to be based on graded perception of negative recordings, from the most intense and unpleasant (assigned to Pain) to the least intense and least unpleasant (assigned to Demand for Food). Parenthood and younger age, but not gender of listeners, had weak positive effects on the accuracy of judgments. Our results indicate that adults almost flawlessly distinguish positive and negative infant sounds, but are rather inaccurate regarding identification of the specific needs of the infant and may normally employ other sensory channels to gain this information.

  14. Antibodies with specificity to native gp120 and neutralization activity against primary human immunodeficiency virus type 1 isolates elicited by immunization with oligomeric gp160.

    PubMed Central

    VanCott, T C; Mascola, J R; Kaminski, R W; Kalyanaraman, V; Hallberg, P L; Burnett, P R; Ulrich, J T; Rechtman, D J; Birx, D L

    1997-01-01

    Current human immunodeficiency virus type 1 (HIV-1) envelope vaccine candidates elicit high antibody binding titers with neutralizing activity against T-cell line-adapted but not primary HIV-1 isolates. Serum antibodies from these human vaccine recipients were also found to be preferentially directed to linear epitopes within gp120 that are poorly exposed on native gp120. Systemic immunization of rabbits with an affinity-purified oligomeric gp160 protein formulated with either Alhydrogel or monophosphoryl lipid A-containing adjuvants resulted in the induction of high-titered serum antibodies that preferentially bound epitopes exposed on native forms of gp120 and gp160, recognized a restricted number of linear epitopes, efficiently bound heterologous strains of monomeric gp120 and cell surface-expressed oligomeric gp120/gp41, and neutralized several strains of T-cell line-adapted HIV-1. Additionally, those immune sera with the highest oligomeric gp160 antibody binding titers had neutralizing activity against some primary HIV-1 isolates, using phytohemagglutinin-stimulated peripheral blood mononuclear cell targets. Induction of an antibody response preferentially reactive with natively folded gp120/gp160 was dependent on the tertiary structure of the HIV-1 envelope immunogen as well as its adjuvant formulation, route of administration, and number of immunizations administered. These studies demonstrate the capacity of a soluble HIV-1 envelope glycoprotein vaccine to elicit an antibody response capable of neutralizing primary HIV-1 isolates. PMID:9151820

  15. Live Attenuated Influenza Vaccine Strains Elicit a Greater Innate Immune Response than Antigenically-Matched Seasonal Influenza Viruses during Infection of Human Nasal Epithelial Cell Cultures

    PubMed Central

    Fischer, William A.; Brighton, Missy; Jaspers, Ilona

    2014-01-01

    Influenza viruses are global pathogens that infect approximately 10–20% of the world’s population each year. Vaccines, including the live attenuated influenza vaccine (LAIV), are the best defense against influenza infections. The LAIV is a novel vaccine that actively replicates in the human nasal epithelium and elicits both mucosal and systemic protective immune responses. The differences in replication and innate immune responses following infection of human nasal epithelium with influenza seasonal wild type (WT) and LAIV viruses remain unknown. Using a model of primary differentiated human nasal epithelial cell (hNECs) cultures, we compared influenza WT and antigenically-matched cold adapted (CA) LAIV virus replication and the subsequent innate immune response including host cellular pattern recognition protein expression, host innate immune gene expression, secreted pro-inflammatory cytokine production, and intracellular viral RNA levels. Growth curves comparing virus replication between WT and LAIV strains revealed significantly less infectious virus production during LAIV compared with WT infection. Despite this disparity in infectious virus production the LAIV strains elicited a more robust innate immune response with increased expression of RIG-I, TLR-3, IFNβ, STAT-1, IRF-7, MxA, and IP-10. There were no differences in cytotoxicity between hNEC cultures infected with WT and LAIV strains as measured by basolateral levels of LDH. Elevated levels of intracellular viral RNA during LAIV as compared with WT virus infection of hNEC cultures at 33°C may explain the augmented innate immune response via the up-regulation of pattern recognition receptors and down-stream type I IFN expression. Taken together our results suggest that the decreased replication of LAIV strains in human nasal epithelial cells is associated with a robust innate immune response that differs from infection with seasonal influenza viruses, limits LAIV shedding and plays a role in the

  16. Live attenuated influenza vaccine strains elicit a greater innate immune response than antigenically-matched seasonal influenza viruses during infection of human nasal epithelial cell cultures.

    PubMed

    Fischer, William A; Chason, Kelly D; Brighton, Missy; Jaspers, Ilona

    2014-03-26

    Influenza viruses are global pathogens that infect approximately 10-20% of the world's population each year. Vaccines, including the live attenuated influenza vaccine (LAIV), are the best defense against influenza infections. The LAIV is a novel vaccine that actively replicates in the human nasal epithelium and elicits both mucosal and systemic protective immune responses. The differences in replication and innate immune responses following infection of human nasal epithelium with influenza seasonal wild type (WT) and LAIV viruses remain unknown. Using a model of primary differentiated human nasal epithelial cell (hNECs) cultures, we compared influenza WT and antigenically-matched cold adapted (CA) LAIV virus replication and the subsequent innate immune response including host cellular pattern recognition protein expression, host innate immune gene expression, secreted pro-inflammatory cytokine production, and intracellular viral RNA levels. Growth curves comparing virus replication between WT and LAIV strains revealed significantly less infectious virus production during LAIV compared with WT infection. Despite this disparity in infectious virus production the LAIV strains elicited a more robust innate immune response with increased expression of RIG-I, TLR-3, IFNβ, STAT-1, IRF-7, MxA, and IP-10. There were no differences in cytotoxicity between hNEC cultures infected with WT and LAIV strains as measured by basolateral levels of LDH. Elevated levels of intracellular viral RNA during LAIV as compared with WT virus infection of hNEC cultures at 33°C may explain the augmented innate immune response via the up-regulation of pattern recognition receptors and down-stream type I IFN expression. Taken together our results suggest that the decreased replication of LAIV strains in human nasal epithelial cells is associated with a robust innate immune response that differs from infection with seasonal influenza viruses, limits LAIV shedding and plays a role in the silent

  17. Antibody-driven design of a human cytomegalovirus gHgLpUL128L subunit vaccine that selectively elicits potent neutralizing antibodies.

    PubMed

    Kabanova, Anna; Perez, Laurent; Lilleri, Daniele; Marcandalli, Jessica; Agatic, Gloria; Becattini, Simone; Preite, Silvia; Fuschillo, Dario; Percivalle, Elena; Sallusto, Federica; Gerna, Giuseppe; Corti, Davide; Lanzavecchia, Antonio

    2014-12-16

    The use of neutralizing antibodies to identify the most effective antigen has been proposed as a strategy to design vaccines capable of eliciting protective B-cell immunity. In this study, we analyzed the human antibody response to cytomegalovirus (human cytomegalovirus, HCMV) infection and found that antibodies to glycoprotein (g)B, a surface glycoprotein that has been developed as a HCMV vaccine, were primarily nonneutralizing. In contrast, most of the antibodies to the complex formed by gH, gL, protein (p)UL128, pUL130, and pUL131 (the gHgLpUL128L pentamer) neutralized HCMV infection with high potency. Based on this analysis, we developed a single polycistronic vector encoding the five pentamer genes separated by "self-cleaving" 2A peptides to generate a stably transfected CHO cell line constitutively secreting high levels of recombinant pentamer that displayed the functional antigenic sites targeted by human neutralizing antibodies. Immunization of mice with the pentamer formulated with different adjuvants elicited HCMV neutralizing antibody titers that persisted to high levels over time and that were a hundred- to thousand-fold higher than those found in individuals that recovered from primary HCMV infection. Sera from mice immunized with the pentamer vaccine neutralized infection of both epithelial cells and fibroblasts and prevented cell-to-cell spread and viral dissemination from endothelial cells to leukocytes. Neutralizing monoclonal antibodies from immunized mice showed the same potency as human antibodies and targeted the same as well as additional sites on the pentamer. These results illustrate with a relevant example a general and practical approach of analytic vaccinology for the development of subunit vaccines against complex pathogens.

  18. Cerebral cortical respiratory-related evoked potentials elicited by inspiratory occlusion in lambs.

    PubMed

    Davenport, Paul W; Hutchison, Alastair A

    2002-07-01

    Respiratory-related evoked potentials (RREP) elicited by inspiratory mechanical loads have been recorded in humans. Early RREP peaks were hypothesized to be generated by activation of neurons in the somatosensory cortex. An animal model was developed to test this hypothesis in chronically instrumented, awake, spontaneously breathing lambs. Electrocorticogram (ECoG) was recorded bilaterally with ball electrodes on the dural surface over the somatosensory region. Inspiratory occlusions were presented through a face mask or endotracheal tube as interruptions of inspiration. Occlusion-elicited evoked potentials were obtained by computer-signal averaging the ECoG activity. A short-latency positive peak was observed bilaterally in the averaged occlusion-elicited evoked potentials in all animals breathing with the facemask and 5 of 8 lambs with the endotracheal tube. Postmortem identification of the electrode location demonstrated that the ECoG was recorded in the caudal-lateral portion of the somatosensory cortex. These results demonstrate that inspiratory occlusion elicits an evoked potential in the somatosensory cortical region of awake, spontaneously breathing lambs. The lamb cortical RREP is similar to human RREP.

  19. Human Carboxylesterase 1 Stereoselectively Binds the Nerve Agent Cyclosarin and Spontaneously Hydrolyzes the Nerve Agent Sarin

    SciTech Connect

    Hemmert, Andrew C.; Otto, Tamara C.; Wierdl, Monika; Edwards, Carol C.; Fleming, Christopher D.; MacDonald, Mary; Cashman, John R.; Potter, Philip M.; Cerasoli, Douglas M.; Redinbo, Matthew R.

    2010-10-28

    Organophosphorus (OP) nerve agents are potent toxins that inhibit cholinesterases and produce a rapid and lethal cholinergic crisis. Development of protein-based therapeutics is being pursued with the goal of preventing nerve agent toxicity and protecting against the long-term side effects of these agents. The drug-metabolizing enzyme human carboxylesterase 1 (hCE1) is a candidate protein-based therapeutic because of its similarity in structure and function to the cholinesterase targets of nerve agent poisoning. However, the ability of wild-type hCE1 to process the G-type nerve agents sarin and cyclosarin has not been determined. We report the crystal structure of hCE1 in complex with the nerve agent cyclosarin. We further use stereoselective nerve agent analogs to establish that hCE1 exhibits a 1700- and 2900-fold preference for the P{sub R} enantiomers of analogs of soman and cyclosarin, respectively, and a 5-fold preference for the P{sub S} isomer of a sarin analog. Finally, we show that for enzyme inhibited by racemic mixtures of bona fide nerve agents, hCE1 spontaneously reactivates in the presence of sarin but not soman or cyclosarin. The addition of the neutral oxime 2,3-butanedione monoxime increases the rate of reactivation of hCE1 from sarin inhibition by more than 60-fold but has no effect on reactivation with the other agents examined. Taken together, these data demonstrate that hCE1 is only reactivated after inhibition with the more toxic P{sub S} isomer of sarin. These results provide important insights toward the long-term goal of designing novel forms of hCE1 to act as protein-based therapeutics for nerve agent detoxification.

  20. Human Carboxylesterase 1 Stereoselectively Binds the Nerve Agent Cyclosarin and Spontaneously Hydrolyzes the Nerve Agent Sarin

    PubMed Central

    Hemmert, Andrew C.; Otto, Tamara C.; Wierdl, Monika; Edwards, Carol C.; Fleming, Christopher D.; MacDonald, Mary; Cashman, John R.; Potter, Philip M.; Cerasoli, Douglas M.

    2010-01-01

    Organophosphorus (OP) nerve agents are potent toxins that inhibit cholinesterases and produce a rapid and lethal cholinergic crisis. Development of protein-based therapeutics is being pursued with the goal of preventing nerve agent toxicity and protecting against the long-term side effects of these agents. The drug-metabolizing enzyme human carboxylesterase 1 (hCE1) is a candidate protein-based therapeutic because of its similarity in structure and function to the cholinesterase targets of nerve agent poisoning. However, the ability of wild-type hCE1 to process the G-type nerve agents sarin and cyclosarin has not been determined. We report the crystal structure of hCE1 in complex with the nerve agent cyclosarin. We further use stereoselective nerve agent analogs to establish that hCE1 exhibits a 1700- and 2900-fold preference for the PR enantiomers of analogs of soman and cyclosarin, respectively, and a 5-fold preference for the PS isomer of a sarin analog. Finally, we show that for enzyme inhibited by racemic mixtures of bona fide nerve agents, hCE1 spontaneously reactivates in the presence of sarin but not soman or cyclosarin. The addition of the neutral oxime 2,3-butanedione monoxime increases the rate of reactivation of hCE1 from sarin inhibition by more than 60-fold but has no effect on reactivation with the other agents examined. Taken together, these data demonstrate that hCE1 is only reactivated after inhibition with the more toxic PS isomer of sarin. These results provide important insights toward the long-term goal of designing novel forms of hCE1 to act as protein-based therapeutics for nerve agent detoxification. PMID:20051531

  1. Differences in the number of micronucleated erythrocytes among young and adult animals including humans. Spontaneous micronuclei in 43 species.

    PubMed

    Zúñiga-González, G; Torres-Bugarín, O; Zamora-Perez, A; Gómez-Meda, B C; Ramos Ibarra, M L; Martínez-González, S; González-Rodríguez, A; Luna-Aguirre, J; Ramos-Mora, A; Ontiveros-Lira, D; Gallegos-Arreola, M P

    2001-07-25

    In our previous report we speculated about the possibility that some species had high levels of spontaneous micronucleated erythrocytes (MNE) just in a juvenile stage, this is, that the MNE diminish as the reticuloendothelial system matures. Here we show this effect in species including rat, rabbit, pig, dog, cat, gray squirrel, lion, giraffe, white-tailed deer, opossum and even human. The number of spontaneous MNE that we found in 43 species is shown, and the proportions of polychromatic and normochromatic. This is our third report on spontaneous MNE in different species. We obtained 189 peripheral blood samples of mammals, birds and reptiles. From 12 species we obtained only one sample, and 16 were reported previously, but now the size of the sample has been increased. The species with the highest spontaneous MNE were the Vietnamese potbelly pig (with the highest MNE number), Bengal tiger, capuchin monkey, puma, ferret, owl, hedgehog, squirrel monkey, pig and white-tailed deer. These species could be used as monitors for genotoxic events.

  2. Differences in the number of micronucleated erythrocytes among young and adult animals including humans. Spontaneous micronuclei in 43 species.

    PubMed

    Zúñiga-González, G; Torres-Bugarín, O; Zamora-Perez, A; Gómez-Meda, B C; Ramos Ibarra, M L; Martínez-González, S; González-Rodríguez, A; Luna-Aguirre, J; Ramos-Mora, A; Ontiveros-Lira, D; Gallegos-Arreola, M P

    2001-07-25

    In our previous report we speculated about the possibility that some species had high levels of spontaneous micronucleated erythrocytes (MNE) just in a juvenile stage, this is, that the MNE diminish as the reticuloendothelial system matures. Here we show this effect in species including rat, rabbit, pig, dog, cat, gray squirrel, lion, giraffe, white-tailed deer, opossum and even human. The number of spontaneous MNE that we found in 43 species is shown, and the proportions of polychromatic and normochromatic. This is our third report on spontaneous MNE in different species. We obtained 189 peripheral blood samples of mammals, birds and reptiles. From 12 species we obtained only one sample, and 16 were reported previously, but now the size of the sample has been increased. The species with the highest spontaneous MNE were the Vietnamese potbelly pig (with the highest MNE number), Bengal tiger, capuchin monkey, puma, ferret, owl, hedgehog, squirrel monkey, pig and white-tailed deer. These species could be used as monitors for genotoxic events. PMID:11423355

  3. Human papillomavirus type 16 virus-like particles expressed in attenuated Salmonella typhimurium elicit mucosal and systemic neutralizing antibodies in mice.

    PubMed Central

    Nardelli-Haefliger, D; Roden, R B; Benyacoub, J; Sahli, R; Kraehenbuhl, J P; Schiller, J T; Lachat, P; Potts, A; De Grandi, P

    1997-01-01

    Attenuated strains of Salmonella are attractive live vaccine candidates for eliciting mucosal as well as systemic immune responses. The ability to induce immune responses in the reproductive tract may be critical for the effectiveness of a prophylactic vaccine against genital human papillomaviruses (HPV), which are important etiologic agents in the development of cervical cancer. To examine the potential of a live Salmonella-based vaccine to prevent genital HPV infection, the L1 major capsid protein from HPV type 16 (HPV16) was constitutively expressed in the PhoPc strain of Salmonella typhimurium. As demonstrated by electron microscopy, the L1 protein expressed in these bacteria assembled into virus-like particles (VLPs) that resemble authentic papillomavirus virions. This is the first demonstration that papillomavirus VLPs can self-assemble in prokaryotes. BALB/c mice were immunized with the HPV16 L1 recombinant PhoPc strain by the oral and nasal routes. Despite a low stability of the L1-expressing plasmid in vivo, a double nasal immunization was effective in inducing L1-specific serum antibodies that recognized mainly native, but not disassembled, VLPs. These antibodies effectively neutralized HPV16 pseudotyped virions in an in vitro infectivity assay. Conformationally dependent anti-VLP immunoglobulin A (IgA) and IgG were also detected in oral and vaginal secretions, indicating that potentially protective antibody responses were elicited at mucosal sites. Recombinant attenuated Salmonella expressing HPV capsids may represent a promising vaccine candidate against genital HPV infection. PMID:9234794

  4. Human Cytomegalovirus UL76 Elicits Novel Aggresome Formation via Interaction with S5a of the Ubiquitin Proteasome System

    PubMed Central

    Lin, Shin-Rung; Jiang, Meei Jyh; Wang, Hung-Hsueh; Hu, Cheng-Hui; Hsu, Ming-Shan; Hsi, Edward; Duh, Chang-Yih

    2013-01-01

    HCMV UL76 is a member of a conserved Herpesviridae protein family (Herpes_UL24) that is involved in viral production, latency, and reactivation. UL76 presents as globular aggresomes in the nuclei of transiently transfected cells. Bioinformatic analyses predict that UL76 has a propensity for aggregation and targets cellular proteins implicated in protein folding and ubiquitin-proteasome systems (UPS). Furthermore, fluorescence recovery after photobleaching experiments suggests that UL76 reduces protein mobility in the aggresome, which indicates that UL76 elicits the aggregation of misfolded proteins. Moreover, in the absence of other viral proteins, UL76 interacts with S5a, which is a major receptor of polyubiquitinated proteins for UPS proteolysis via its conserved region and the von Willebrand factor type A (VWA) domain of S5a. We demonstrate that UL76 sequesters polyubiquitinated proteins and S5a to nuclear aggresomes in biological proximity. After knockdown of endogenous S5a by RNA interference techniques, the UL76 level was only minimally affected in transiently expressing cells. However, a significant reduction in the number of cells containing UL76 nuclear aggresomes was observed, which suggests that S5a may play a key role in aggresome formation. Moreover, we show that UL76 interacts with S5a in the late phase of viral infection and that knockdown of S5a hinders the development of both the replication compartment and the aggresome. In this study, we demonstrate that UL76 induces a novel nuclear aggresome, likely by subverting S5a of the UPS. Given that UL76 belongs to a conserved family, this underlying mechanism may be shared by all members of the Herpesviridae. PMID:23966401

  5. Spontaneous recovery in human instrumental learning: Integration of information and recency to primacy shift.

    PubMed

    López-Romero, Luis Jesús; García-Barraza, Rodolfo; Vila, Javier

    2010-06-01

    This experiment was conducted to study the effect of changes in the retention interval (RI) on spontaneous recovery within an acquisition-test interference task. College students learned a reversal conditional discrimination to solve a task involving conflicting phases across two training phases. When the test was conducted immediately after training, participants' performance revealed recency, behaving according to the information received during the last phase. Performance after retention interval averaged the information received across phases, regardless of the length of the RI (1.5, 3, 24 or 48 h). These results are not in agreement with traditional theories of spontaneous recovery as they predict a recency to primacy shift effect of the RI. An interpretation of spontaneous recovery based on a temporal weighting rule (TWR) is discussed.

  6. HIV-Tat Induces the Nrf2/ARE Pathway through NMDA Receptor-Elicited Spermine Oxidase Activation in Human Neuroblastoma Cells

    PubMed Central

    Mastrantonio, Roberta; Cervelli, Manuela; Pietropaoli, Stefano; Mariottini, Paolo; Colasanti, Marco; Persichini, Tiziana

    2016-01-01

    Previously, we reported that HIV-Tat elicits spermine oxidase (SMO) activity upregulation through NMDA receptor (NMDAR) stimulation in human SH-SY5Y neuroblastoma cells, thus increasing ROS generation, which in turn leads to GSH depletion, oxidative stress, and reduced cell viability. In several cell types, ROS can trigger an antioxidant cell response through the transcriptional induction of oxidative stress-responsive genes regulated by the nuclear factor erythroid 2-related factor 2 (Nrf2). Here, we demonstrate that Tat induces both antioxidant gene expression and Nrf2 activation in SH-SY5Y cells, mediated by SMO activity. Furthermore, NMDAR is involved in Tat-induced Nrf2 activation. These findings suggest that the NMDAR/SMO/Nrf2 pathway is an important target for protection against HIV-associated neurocognitive disorders. PMID:26895301

  7. Flaws in current human training protocols for spontaneous Brain-Computer Interfaces: lessons learned from instructional design

    PubMed Central

    Lotte, Fabien; Larrue, Florian; Mühl, Christian

    2013-01-01

    While recent research on Brain-Computer Interfaces (BCI) has highlighted their potential for many applications, they remain barely used outside laboratories. The main reason is their lack of robustness. Indeed, with current BCI, mental state recognition is usually slow and often incorrect. Spontaneous BCI (i.e., mental imagery-based BCI) often rely on mutual learning efforts by the user and the machine, with BCI users learning to produce stable ElectroEncephaloGraphy (EEG) patterns (spontaneous BCI control being widely acknowledged as a skill) while the computer learns to automatically recognize these EEG patterns, using signal processing. Most research so far was focused on signal processing, mostly neglecting the human in the loop. However, how well the user masters the BCI skill is also a key element explaining BCI robustness. Indeed, if the user is not able to produce stable and distinct EEG patterns, then no signal processing algorithm would be able to recognize them. Unfortunately, despite the importance of BCI training protocols, they have been scarcely studied so far, and used mostly unchanged for years. In this paper, we advocate that current human training approaches for spontaneous BCI are most likely inappropriate. We notably study instructional design literature in order to identify the key requirements and guidelines for a successful training procedure that promotes a good and efficient skill learning. This literature study highlights that current spontaneous BCI user training procedures satisfy very few of these requirements and hence are likely to be suboptimal. We therefore identify the flaws in BCI training protocols according to instructional design principles, at several levels: in the instructions provided to the user, in the tasks he/she has to perform, and in the feedback provided. For each level, we propose new research directions that are theoretically expected to address some of these flaws and to help users learn the BCI skill more

  8. Flaws in current human training protocols for spontaneous Brain-Computer Interfaces: lessons learned from instructional design.

    PubMed

    Lotte, Fabien; Larrue, Florian; Mühl, Christian

    2013-01-01

    While recent research on Brain-Computer Interfaces (BCI) has highlighted their potential for many applications, they remain barely used outside laboratories. The main reason is their lack of robustness. Indeed, with current BCI, mental state recognition is usually slow and often incorrect. Spontaneous BCI (i.e., mental imagery-based BCI) often rely on mutual learning efforts by the user and the machine, with BCI users learning to produce stable ElectroEncephaloGraphy (EEG) patterns (spontaneous BCI control being widely acknowledged as a skill) while the computer learns to automatically recognize these EEG patterns, using signal processing. Most research so far was focused on signal processing, mostly neglecting the human in the loop. However, how well the user masters the BCI skill is also a key element explaining BCI robustness. Indeed, if the user is not able to produce stable and distinct EEG patterns, then no signal processing algorithm would be able to recognize them. Unfortunately, despite the importance of BCI training protocols, they have been scarcely studied so far, and used mostly unchanged for years. In this paper, we advocate that current human training approaches for spontaneous BCI are most likely inappropriate. We notably study instructional design literature in order to identify the key requirements and guidelines for a successful training procedure that promotes a good and efficient skill learning. This literature study highlights that current spontaneous BCI user training procedures satisfy very few of these requirements and hence are likely to be suboptimal. We therefore identify the flaws in BCI training protocols according to instructional design principles, at several levels: in the instructions provided to the user, in the tasks he/she has to perform, and in the feedback provided. For each level, we propose new research directions that are theoretically expected to address some of these flaws and to help users learn the BCI skill more

  9. Eicosanomic profiling reveals dominance of the epoxygenase pathway in human amniotic fluid at term in spontaneous labor.

    PubMed

    Maddipati, Krishna Rao; Romero, Roberto; Chaiworapongsa, Tinnakorn; Zhou, Sen-Lin; Xu, Zhonghui; Tarca, Adi L; Kusanovic, Juan Pedro; Munoz, Hernan; Honn, Kenneth V

    2014-11-01

    Lipid mediators play an important role in reproductive biology, especially, in parturition. Enhanced biosynthesis of eicosanoids, such as prostaglandin E2 (PGE2) and PGF2α, precedes the onset of labor as a result of increased expression of inducible cyclooxygenase 2 (COX-2) in placental tissues. Metabolism of arachidonic acid results in bioactive lipid mediators beyond prostaglandins that could significantly influence myometrial activity. Therefore, an unbiased lipidomic approach was used to profile the arachidonic acid metabolome of amniotic fluid. In this study, liquid chromatography-mass spectrometry was used for the first time to quantitate these metabolites in human amniotic fluid by comparing patients at midtrimester, at term but not in labor, and at term and in spontaneous labor. In addition to exposing novel aspects of COX pathway metabolism, this lipidomic study revealed a dramatic increase in epoxygenase- and lipoxygenase-pathway-derived lipid mediators in spontaneous labor with remarkable product selectivity. Despite their recognition as anti-inflammatory lipid mediators and regulators of ion channels, little is known about the epoxygenase pathway in labor. Epoxygenase pathway metabolites are established regulators of vascular homeostasis in cardiovascular and renal physiology. Their presence as the dominant lipid mediators in spontaneous labor at term portends a yet undiscovered physiological function in parturition.

  10. FOXO3a elicits a pro-apoptotic transcription program and cellular response to human lung carcinogen nicotine-derived nitrosaminoketone (NNK).

    PubMed

    Blake, Daniel C; Mikse, Oliver R; Freeman, Willard M; Herzog, Christopher R

    2010-01-01

    Long-term carcinogen exposure exerts continuous pressure on key mechanisms that repair or eliminate carcinogen-damaged cells giving rise to selective failures that contribute to lung cancer. FOXO3a is a transcription factor that elicits a protective response to diverse cellular stresses. Although implicated as a tumor suppressor, its role in sporadic cancer is uncertain. We recently observed that FOXO3a gene inactivation occurs frequently in carcinogen-induced lung adenocarcinoma (LAC). This suggests that FOXO3a may play a role in LAC suppression by eliciting a protective response to carcinogenic stress. Here we investigated this possibility by examining the role of FOXO3a in the cellular response to nicotine-derived nitrosaminoketone (NNK), a lung carcinogen implicated as a cause of human LAC. We show that restoration of FOXO3a in FOXO3a-deficient LAC cells increases sensitivity to apoptosis caused by a DNA-damaging intermediate of NNK. Prior to this cellular outcome, FOXO3a is functionally activated and mediates a large-scale transcription program in response to this damage involving a significant modulation of 440 genes. Genes most significantly represented in this program are those with roles in cell growth and proliferation>protein synthesis>gene expression>cell death>cell cycle. The results of this study show that FOXO3a directs an anti-carcinogenic transcription program that culminates in the elimination of carcinogen-damaged cells. This suggests that FOXO3a is a potential suppressor of carcinogenic damage in LAC. PMID:19380174

  11. Videos of conspecifics elicit interactive looking patterns and facial expressions in monkeys.

    PubMed

    Mosher, Clayton P; Zimmerman, Prisca E; Gothard, Katalin M

    2011-08-01

    A broader understanding of the neural basis of social behavior in primates requires the use of species-specific stimuli that elicit spontaneous, but reproducible and tractable behaviors. In this context of natural behaviors, individual variation can further inform about the factors that influence social interactions. To approximate natural social interactions similar to those documented by field studies, we used unedited video footage to induce in viewer monkeys spontaneous facial expressions and looking patterns in the laboratory setting. Three adult male monkeys (Macaca mulatta), previously behaviorally and genetically (5-HTTLPR) characterized, were monitored while they watched 10 s video segments depicting unfamiliar monkeys (movie monkeys) displaying affiliative, neutral, and aggressive behaviors. The gaze and head orientation of the movie monkeys alternated between "averted" and "directed" at the viewer. The viewers were not reinforced for watching the movies, thus their looking patterns indicated their interest and social engagement with the stimuli. The behavior of the movie monkey accounted for differences in the looking patterns and facial expressions displayed by the viewers. We also found multiple significant differences in the behavior of the viewers that correlated with their interest in these stimuli. These socially relevant dynamic stimuli elicited spontaneous social behaviors, such as eye-contact induced reciprocation of facial expression, gaze aversion, and gaze following, that were previously not observed in response to static images. This approach opens a unique opportunity to understanding the mechanisms that trigger spontaneous social behaviors in humans and nonhuman primates.

  12. Brucella invasion of human intestinal epithelial cells elicits a weak proinflammatory response but a significant CCL20 secretion.

    PubMed

    Ferrero, Mariana C; Fossati, Carlos A; Rumbo, Martín; Baldi, Pablo C

    2012-10-01

    In spite of the frequent acquisition of Brucella infection by the oral route in humans, the interaction of the bacterium with cells of the intestinal mucosa has been poorly studied. Here, we show that different Brucella species can invade human colonic epithelial cell lines (Caco-2 and HT-29), in which only smooth species can replicate efficiently. Infection with smooth strains did not produce a significant cytotoxicity, while the rough strain RB51 was more cytotoxic. Infection of Caco-2 cells or HT-29 cells with either smooth or rough strains of Brucella did not result in an increased secretion of TNF-α, IL-1β, MCP-1, IL-10 or TGF-β as compared with uninfected controls, whereas all the infections induced the secretion of IL-8 and CCL20 by both cell types. The MCP-1 response to flagellin from Salmonella typhimurium was similar in Brucella-infected or uninfected cells, ruling out a bacterial inhibitory mechanism as a reason for the weak proinflammatory response. Infection did not modify ICAM-1 expression levels in Caco-2 cells, but increased them in HT-29 cells. These results suggest that Brucella induces only a weak proinflammatory response in gut epithelial cells, but produces a significant CCL20 secretion. The latter may be important for bacterial dissemination given the known ability of Brucella to survive in dendritic cells. PMID:22553918

  13. Delayed Extinction Attenuates Conditioned Fear Renewal and Spontaneous Recovery in Humans

    PubMed Central

    Huff, Nicole C.; Hernandez, Jose Alba; Blanding, Nineequa Q.; LaBar, Kevin S.

    2009-01-01

    This study investigated whether the retention interval after an aversive learning experience influences the return of fear after extinction training. After fear conditioning, participants underwent extinction training either 5 min or 1 day later and in either the same room (same context) or a different room (context shift). The next day, conditioned fear was tested in the original room. When extinction took place immediately, fear renewal was robust and prolonged for context-shift participants, and spontaneous recovery was observed in the same-context participants. Delayed extinction, by contrast, yielded a brief form of fear renewal that reextinguished within the testing session for context-shift participants, and there was no spontaneous recovery in the same-context participants. The authors conclude that the passage of time allows for memory consolidation processes to promote the formation of distinct yet flexible emotional memory traces that confer an ability to recall extinction, even in an alternate context, and minimize the return of fear. Furthermore, immediate extinction can yield spontaneous recovery and prolong fear renewal. These findings have potential implications for ameliorating fear relapse in anxiety disorders. PMID:19634943

  14. The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans.

    PubMed

    May, Patrick C; Willis, Brian A; Lowe, Stephen L; Dean, Robert A; Monk, Scott A; Cocke, Patrick J; Audia, James E; Boggs, Leonard N; Borders, Anthony R; Brier, Richard A; Calligaro, David O; Day, Theresa A; Ereshefsky, Larry; Erickson, Jon A; Gevorkyan, Hykop; Gonzales, Celedon R; James, Douglas E; Jhee, Stanford S; Komjathy, Steven F; Li, Linglin; Lindstrom, Terry D; Mathes, Brian M; Martényi, Ferenc; Sheehan, Scott M; Stout, Stephanie L; Timm, David E; Vaught, Grant M; Watson, Brian M; Winneroski, Leonard L; Yang, Zhixiang; Mergott, Dustin J

    2015-01-21

    BACE1 is a key protease controlling the formation of amyloid β, a peptide hypothesized to play a significant role in the pathogenesis of Alzheimer's disease (AD). Therefore, the development of potent and selective inhibitors of BACE1 has been a focus of many drug discovery efforts in academia and industry. Herein, we report the nonclinical and early clinical development of LY2886721, a BACE1 active site inhibitor that reached phase 2 clinical trials in AD. LY2886721 has high selectivity against key off-target proteases, which efficiently translates in vitro activity into robust in vivo amyloid β lowering in nonclinical animal models. Similar potent and persistent amyloid β lowering was observed in plasma and lumbar CSF when single and multiple doses of LY2886721 were administered to healthy human subjects. Collectively, these data add support for BACE1 inhibition as an effective means of amyloid lowering and as an attractive target for potential disease modification therapy in AD. PMID:25609634

  15. The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans.

    PubMed

    May, Patrick C; Willis, Brian A; Lowe, Stephen L; Dean, Robert A; Monk, Scott A; Cocke, Patrick J; Audia, James E; Boggs, Leonard N; Borders, Anthony R; Brier, Richard A; Calligaro, David O; Day, Theresa A; Ereshefsky, Larry; Erickson, Jon A; Gevorkyan, Hykop; Gonzales, Celedon R; James, Douglas E; Jhee, Stanford S; Komjathy, Steven F; Li, Linglin; Lindstrom, Terry D; Mathes, Brian M; Martényi, Ferenc; Sheehan, Scott M; Stout, Stephanie L; Timm, David E; Vaught, Grant M; Watson, Brian M; Winneroski, Leonard L; Yang, Zhixiang; Mergott, Dustin J

    2015-01-21

    BACE1 is a key protease controlling the formation of amyloid β, a peptide hypothesized to play a significant role in the pathogenesis of Alzheimer's disease (AD). Therefore, the development of potent and selective inhibitors of BACE1 has been a focus of many drug discovery efforts in academia and industry. Herein, we report the nonclinical and early clinical development of LY2886721, a BACE1 active site inhibitor that reached phase 2 clinical trials in AD. LY2886721 has high selectivity against key off-target proteases, which efficiently translates in vitro activity into robust in vivo amyloid β lowering in nonclinical animal models. Similar potent and persistent amyloid β lowering was observed in plasma and lumbar CSF when single and multiple doses of LY2886721 were administered to healthy human subjects. Collectively, these data add support for BACE1 inhibition as an effective means of amyloid lowering and as an attractive target for potential disease modification therapy in AD.

  16. Increasing Dietary Fat Elicits Similar Changes in Fat Oxidation and Markers of Muscle Oxidative Capacity in Lean and Obese Humans

    PubMed Central

    Bergouignan, Audrey; Gozansky, Wendolyn S.; Barry, Daniel W.; Leitner, Wayne; MacLean, Paul S.; Hill, James O.; Draznin, Boris; Melanson, Edward L.

    2012-01-01

    In lean humans, increasing dietary fat intake causes an increase in whole-body fat oxidation and changes in genes that regulate fat oxidation in skeletal muscle, but whether this occurs in obese humans is not known. We compared changes in whole-body fat oxidation and markers of muscle oxidative capacity differ in lean (LN) and obese (OB) adults exposed to a 2-day high-fat (HF) diet. Ten LN (BMI = 22.5±2.5 kg/m2, age = 30±8 yrs) and nine OB (BMI = 35.9±4.93 kg/m2, 38±5 yrs, Mean±SD) were studied in a room calorimeter for 24hr while consuming isocaloric low-fat (LF, 20% of energy) and HF (50% of energy) diets. A muscle biopsy was obtained the next morning following an overnight fast. 24h respiratory quotient (RQ) did not significantly differ between groups (LN: 0.91±0.01; OB: 0.92±0.01) during LF, and similarly decreased during HF in LN (0.86±0.01) and OB (0.85±0.01). The expression of pyruvate dehydrogenase kinase 4 (PDK4) and the fatty acid transporter CD36 increased in both LN and OB during HF. No other changes in mRNA or protein were observed. However, in both LN and OB, the amounts of acetylated peroxisome proliferator-activated receptor γ coactivator-1-α (PGC1-α) significantly decreased and phosphorylated 5-AMP-activated protein kinase (AMPK) significantly increased. In response to an isoenergetic increase in dietary fat, whole-body fat oxidation similarly increases in LN and OB, in association with a shift towards oxidative metabolism in skeletal muscle, suggesting that the ability to adapt to an acute increase in dietary fat is not impaired in obesity. PMID:22253914

  17. The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model.

    PubMed

    Kirkpatrick, Beth D; Whitehead, Stephen S; Pierce, Kristen K; Tibery, Cecilia M; Grier, Palmtama L; Hynes, Noreen A; Larsson, Catherine J; Sabundayo, Beulah P; Talaat, Kawsar R; Janiak, Anna; Carmolli, Marya P; Luke, Catherine J; Diehl, Sean A; Durbin, Anna P

    2016-03-16

    A dengue human challenge model can be an important tool to identify candidate dengue vaccines that should be further evaluated in large efficacy trials in endemic areas. Dengue is responsible for about 390 million infections annually. Protective efficacy results for the most advanced dengue vaccine candidate (CYD) were disappointing despite its ability to induce neutralizing antibodies against all four dengue virus (DENV) serotypes. TV003 is a live attenuated tetravalent DENV vaccine currently in phase 2 evaluation. To better assess the protective efficacy of TV003, a randomized double-blind, placebo-controlled trial in which recipients of TV003 or placebo were challenged 6 months later with a DENV-2 strain, rDEN2Δ30, was conducted. The primary endpoint of the trial was protection against dengue infection, defined as rDEN2Δ30 viremia. Secondary endpoints were protection against rash and neutropenia. All 21 recipients of TV003 who were challenged with rDEN2Δ30 were protected from infection with rDEN2Δ30. None developed viremia, rash, or neutropenia after challenge. In contrast, 100% of the 20 placebo recipients who were challenged with rDEN2Δ30 developed viremia, 80% developed rash, and 20% developed neutropenia. TV003 induced complete protection against challenge with rDEN2Δ30 administered 6 months after vaccination. TV003 will be further evaluated in dengue-endemic areas. The controlled dengue human challenge model can accelerate vaccine development by evaluating the protection afforded by the vaccine, thereby eliminating poor candidates from further consideration before the initiation of large efficacy trials. PMID:27089205

  18. Heat-labile- and heat-stable-toxoid fusions (LTR₁₉₂G-STaP₁₃F) of human enterotoxigenic Escherichia coli elicit neutralizing antitoxin antibodies.

    PubMed

    Liu, Mei; Ruan, Xiaosai; Zhang, Chengxian; Lawson, Steve R; Knudsen, David E; Nataro, James P; Robertson, Donald C; Zhang, Weiping

    2011-10-01

    Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of diarrheal disease in humans and animals. Adhesins and enterotoxins, including heat-labile (LT) and heat-stable (STa) toxins, are the key virulence factors. Antigenic adhesin and LT antigens have been used in developing vaccines against ETEC diarrhea. However, STa has not been included because of its poor immunogenicity and potent toxicity. Our recent study showed that porcine-type STa toxoids became immunogenic and elicited neutralizing anti-STa antibodies after being genetically fused to a full-length porcine-type LT toxoid, LT(R₁₉₂G) (W. Zhang et al., Infect. Immun. 78:316-325, 2010). In this study, we mutated human-type LT and STa genes, which are highly homologous to porcine-type toxin genes, for a full-length LT toxoid (LT(R₁₉₂)) and a full-length STa toxoid (STa(P₁₃F)) and genetically fused them to produce LT₁₉₂-STa₁₃ toxoid fusions. Mice immunized with LT₁₉₂-STa₁₃ fusion antigens developed anti-LT and anti-STa IgG (in serum and feces) and IgA antibodies (in feces). Moreover, secretory IgA antibodies from immunized mice were shown to neutralize STa and cholera toxins in T-84 cells. In addition, we fused the STa₁₃ toxoid at the N terminus and C terminus, between the A1 and A2 peptides, and between the A and B subunits of LT₁₉₂ to obtain different fusions in order to explore strategies for enhancing STa immunogenicity. This study demonstrated that human-type LT₁₉₂-STa₁₃ fusions induce neutralizing antitoxin antibodies and provided important information for developing toxoid vaccines against human ETEC diarrhea. PMID:21788385

  19. Cationic surfactants in the form of nanoparticles and micelles elicit different human neutrophil responses: a toxicological study.

    PubMed

    Hwang, Tsong-Long; Sung, Calvin T; Aljuffali, Ibrahim A; Chang, Yuan-Ting; Fang, Jia-You

    2014-02-01

    Cationic surfactants are an ingredient commonly incorporated into nanoparticles for clinical practicability; however, the toxicity of cationic surfactants in nanoparticles is not fully elucidated. We aimed to evaluate the inflammatory responses of cationic nanobubbles and micelles in human neutrophils. Soyaethyl morpholinium ethosulfate (SME) and hexadecyltrimethyl-ammonium bromide (CTAB) are the two cationic surfactants employed in this study. The zeta potential of CTAB nanobubbles was 80 mV, which was the highest among all formulations. Nanobubbles, without cationic surfactants, showed no cytotoxic effects on neutrophils in terms of inflammatory responses. Cationic nanobubbles caused a concentration-dependent cytotoxicity of degranulation (elastase release) and membrane damage (release of lactate dehydrogenase, LDH). Among all nanoparticles and micelles, CTAB-containing nanosystems showed the greatest inflammatory responses. A CTAB nanobubble diluent (1/150) increased the LDH release 80-fold. Propidium iodide staining and scanning electron microscopy (SEM) verified cell death and morphological change of neutrophils treated by CTAB nanobubbles. SME, in a micelle form, strengthened the inflammatory response more than SME-loaded nanobubbles. Membrane interaction and subsequent Ca(2+) influx were the mechanisms that triggered inflammation. The information obtained from this work is beneficial in designing nanoparticulate formulations for balancing clinical activity and toxicity. PMID:24246197

  20. Rhein Elicits In Vitro Cytotoxicity in Primary Human Liver HL-7702 Cells by Inducing Apoptosis through Mitochondria-Mediated Pathway

    PubMed Central

    Bounda, Guy-Armel; Zhou, Wang; Wang, Dan-dan; Yu, Feng

    2015-01-01

    Objective. To study rhein-induced apoptosis signaling pathway and to investigate its molecular mechanisms in primary human hepatic cells. Results. Cell viability of HL-7702 cells treated with rhein showed significant decrease in dose-dependent manner. Following rhein treatment (25 μM, 50 μM, and 100 μM) for 12 h, the detection of apoptotic cells was significantly analyzed by flow cytometry and nuclear morphological changes by Hoechst 33258, respectively. Fatty degeneration studies showed upregulation level of the relevant hepatic markers (P < 0.01). Caspase activities expressed significant upregulation of caspase-3, caspase-9, and caspase-8. Moreover, apoptotic cells by rhein were significantly inhibited by Z-LEHD-FMK and Z-DEVD-FMK, caspase-9 inhibitor, and caspase-3 inhibitor, respectively. Overproduction of reactive oxygen species, lipid peroxidation, and loss of mitochondrial membrane potential were detected by fluorometry. Additionally, NAC, a ROS scavenger, significantly attenuated rhein-induced oxidative damage in HL-7702 cells. Furthermore, real-time qPCR results showed significant upregulation of p53, PUMA, Apaf-1, and Casp-9 and Casp-3 mRNA, with no significant changes of Fas and Cytochrome-c. Immunoblotting revealed significant Cytochrome-c release from mitochondria into cytosol and no change in Fas expression. Conclusion. Taken together, these observations suggested that rhein could induce apoptosis in HL-7702 cells via mitochondria-mediated signal pathway with involvement of oxidative stress mechanism. PMID:26221172

  1. Insight into different environmental niches adaptation and allergenicity from the Cladosporium sphaerospermum genome, a common human allergy-eliciting Dothideomycetes.

    PubMed

    Yew, Su Mei; Chan, Chai Ling; Ngeow, Yun Fong; Toh, Yue Fen; Na, Shiang Ling; Lee, Kok Wei; Hoh, Chee-Choong; Yee, Wai-Yan; Ng, Kee Peng; Kuan, Chee Sian

    2016-05-31

    Cladosporium sphaerospermum, a dematiaceous saprophytic fungus commonly found in diverse environments, has been reported to cause allergy and other occasional diseases in humans. However, its basic biology and genetic information are largely unexplored. A clinical isolate C. sphaerospermum genome, UM 843, was re-sequenced and combined with previously generated sequences to form a model 26.89 Mb genome containing 9,652 predicted genes. Functional annotation on predicted genes suggests the ability of this fungus to degrade carbohydrate and protein complexes. Several putative peptidases responsible for lung tissue hydrolysis were identified. These genes shared high similarity with the Aspergillus peptidases. The UM 843 genome encodes a wide array of proteins involved in the biosynthesis of melanin, siderophores, cladosins and survival in high salinity environment. In addition, a total of 28 genes were predicted to be associated with allergy. Orthologous gene analysis together with 22 other Dothideomycetes showed genes uniquely present in UM 843 that encode four class 1 hydrophobins which may be allergens specific to Cladosporium. The mRNA of these hydrophobins were detected by RT-PCR. The genomic analysis of UM 843 contributes to the understanding of the biology and allergenicity of this widely-prevalent species.

  2. Insight into different environmental niches adaptation and allergenicity from the Cladosporium sphaerospermum genome, a common human allergy-eliciting Dothideomycetes

    PubMed Central

    Yew, Su Mei; Chan, Chai Ling; Ngeow, Yun Fong; Toh, Yue Fen; Na, Shiang Ling; Lee, Kok Wei; Hoh, Chee-Choong; Yee, Wai-Yan; Ng, Kee Peng; Kuan, Chee Sian

    2016-01-01

    Cladosporium sphaerospermum, a dematiaceous saprophytic fungus commonly found in diverse environments, has been reported to cause allergy and other occasional diseases in humans. However, its basic biology and genetic information are largely unexplored. A clinical isolate C. sphaerospermum genome, UM 843, was re-sequenced and combined with previously generated sequences to form a model 26.89 Mb genome containing 9,652 predicted genes. Functional annotation on predicted genes suggests the ability of this fungus to degrade carbohydrate and protein complexes. Several putative peptidases responsible for lung tissue hydrolysis were identified. These genes shared high similarity with the Aspergillus peptidases. The UM 843 genome encodes a wide array of proteins involved in the biosynthesis of melanin, siderophores, cladosins and survival in high salinity environment. In addition, a total of 28 genes were predicted to be associated with allergy. Orthologous gene analysis together with 22 other Dothideomycetes showed genes uniquely present in UM 843 that encode four class 1 hydrophobins which may be allergens specific to Cladosporium. The mRNA of these hydrophobins were detected by RT-PCR. The genomic analysis of UM 843 contributes to the understanding of the biology and allergenicity of this widely-prevalent species. PMID:27243961

  3. Methylation of PLCD1 and adenovirus-mediated PLCD1 overexpression elicits a gene therapy effect on human breast cancer

    SciTech Connect

    Mu, Haixi; Wang, Na; Zhao, Lijuan; Li, Shuman; Li, Qianqian; Chen, Ling; Luo, Xinrong; Qiu, Zhu; Li, Lili; Ren, Guosheng; Xu, Yongzhu; Zhou, Xiangyang; Xiang, Tingxiu

    2015-03-15

    Our previous study showed that PLCD1 significantly decreases cell proliferation and affects cell cycle progression in breast cancer cells. In the present study, we aimed to investigate its functional and molecular mechanisms, and whether or not can become a new target for gene therapies. We found reduced PLCD1 protein expression in breast tumor tissues compared with paired surgical margin tissues. PLCD1 promoter CpG methylation was detected in 55 of 96 (57%) primary breast tumors, but not in surgical-margin tissues and normal breast tissues. Ectopic expression of PLCD1 inhibited breast tumor cell proliferation in vivo by inducing apoptosis and suppressed tumor cell migration by regulating cytoskeletal reorganization proteins including RhoA and phospho-cofilin. Furthermore, we found that PLCD1 induced p53 accumulation, increased p27 and p21 protein levels, and cleaved PARP. Finally, we constructed an adenoviral vector expressing PLCD1 (AdH5-PLCD1), which exhibited strong cytotoxicity in breast cancer cells. Our findings provide insights into the development of PLCD1 gene therapies for breast cancer and perhaps, other human cancers. - Highlights: • PLCD1 is downregulated via hypermethylation in breast cancer. • PLCD1 suppressed cell migration by regulating cytoskeletal reorganization proteins. • Adenovirus AdHu5-PLCD1 may be a novel therapeutic option for breast cancer.

  4. Rhein Elicits In Vitro Cytotoxicity in Primary Human Liver HL-7702 Cells by Inducing Apoptosis through Mitochondria-Mediated Pathway.

    PubMed

    Bounda, Guy-Armel; Zhou, Wang; Wang, Dan-Dan; Yu, Feng

    2015-01-01

    Objective. To study rhein-induced apoptosis signaling pathway and to investigate its molecular mechanisms in primary human hepatic cells. Results. Cell viability of HL-7702 cells treated with rhein showed significant decrease in dose-dependent manner. Following rhein treatment (25 μM, 50 μM, and 100 μM) for 12 h, the detection of apoptotic cells was significantly analyzed by flow cytometry and nuclear morphological changes by Hoechst 33258, respectively. Fatty degeneration studies showed upregulation level of the relevant hepatic markers (P < 0.01). Caspase activities expressed significant upregulation of caspase-3, caspase-9, and caspase-8. Moreover, apoptotic cells by rhein were significantly inhibited by Z-LEHD-FMK and Z-DEVD-FMK, caspase-9 inhibitor, and caspase-3 inhibitor, respectively. Overproduction of reactive oxygen species, lipid peroxidation, and loss of mitochondrial membrane potential were detected by fluorometry. Additionally, NAC, a ROS scavenger, significantly attenuated rhein-induced oxidative damage in HL-7702 cells. Furthermore, real-time qPCR results showed significant upregulation of p53, PUMA, Apaf-1, and Casp-9 and Casp-3 mRNA, with no significant changes of Fas and Cytochrome-c. Immunoblotting revealed significant Cytochrome-c release from mitochondria into cytosol and no change in Fas expression. Conclusion. Taken together, these observations suggested that rhein could induce apoptosis in HL-7702 cells via mitochondria-mediated signal pathway with involvement of oxidative stress mechanism. PMID:26221172

  5. Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity

    PubMed Central

    Vicetti Miguel, Rodolfo D.; Harvey, Stephen A. K.; LaFramboise, William A.; Reighard, Seth D.; Matthews, Dean B.; Cherpes, Thomas L.

    2013-01-01

    While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures. PMID:23555586

  6. Capsaicin exposure elicits complex airway defensive motor patterns in normal humans in a concentration-dependent manner.

    PubMed

    Vovk, A; Bolser, D C; Hey, J A; Danzig, M; Vickroy, T; Berry, R; Martin, A D; Davenport, P W

    2007-01-01

    The airway defensive response to tussive agents, such as capsaicin, is frequently assessed by counting the number of cough sounds, or expulsive events. This method does not identify or differentiate important respiratory events that occur in the respiratory muscles and lungs, which are critical in assessing airway defensive responses. The purpose of this study was to characterize the airway defensive behaviours (cough and expiration reflex) to capsaicin exposure in humans. We observed complex motor behaviours in response to capsaicin exposure. These behaviours were defined as cough reacceleration (CRn) and expiration reflex (ERn), where n is the number of expulsive events with and without a preceding inspiratory phase, respectively. Airway defensive responses were defined in terms of frequency (number of expulsive events), strength (activation of abdominal muscles) and behaviour type (CRn vs. ERn). Thirty-six subjects (15 females, 24+/-4 yr) were instrumented with EMG electrodes placed over the rectus abdominis (RA), external abdominal oblique (EO) and the 8th intercostal space (IC8). A custom-designed mouth pneumotachograph was used to assess the airflow acceleration, plateau velocity and phase duration of the expulsive phase. Subjects inhaled seven concentrations of capsaicin (5-200 microM) in a randomized block order. The total number of expulsive events (frequency) and the sum of integrated EMG for the IC8, RA and EO (strength) increased in a curvilinear fashion. Differentiating the airway defense responses into type demonstrated predominately CR1 and CR2 (i.e. inspiration followed by one and two expulsive events, respectively) with very few ER's at <50 microM capsaicin. At higher concentrations (>50 microM) ER's with one or more expulsive events (ER1) appeared, and the number of CR's with three or more expulsive events (CR3) increased. The decrease in EMG activation and airflow measurements with each successive expulsive event suggests a decline in power and

  7. A model of spontaneous mouse mammary tumor for human estrogen receptor- and progesterone receptor-negative breast cancer

    PubMed Central

    ZHENG, LIXIANG; ZHOU, BUGAO; MENG, XIANMING; ZHU, WEIFENG; ZUO, AIREN; WANG, XIAOMIN; JIANG, RUNDE; YU, SHIPING

    2014-01-01

    Breast cancer (BC) is the most frequently malignancy in women. Therefore, establishment of an animal model for the development of preventative measures and effective treatment for tumors is required. A novel heterogeneous spontaneous mammary tumor animal model of Kunming mice was generated. The purpose of this study was to characterize the spontaneous mammary tumor model. Histopathologically, invasive nodular masses of pleomorphic tubular neoplastic epithelial cells invaded fibro-vascular stroma, adjacent dermis and muscle tissue. Metastatic spread through blood vessel into liver and lungs was observed by hematoxylin eosin staining. No estrogen receptor (ER) or progesterone receptor (PR) immunoreactivity was detected in their associated malignant tumors, human epidermal growth factor receptor-2 (HER-2) protein weak expression was found by immunohistochemistry. High expression of vascular endothelial growth factor (VEGF), moderate or high expression of c-Myc and cyclin D1 were observed in tumor sections at different stages (2, 4, 6 and 8 weeks after cancer being found) when compared with that of the normal mammary glands. The result showed that the model is of an invasive ductal carcinoma. Remarkably in the mouse model, ER and PR-negative and HER2 weak positivity are observed. The high or moderate expressions of breast cancer markers (VEGF, c-Myc and cyclin D1) in mammary cancer tissue change at different stages. To our knowledge, this is the first report of a spontaneous mammary model displaying colony-strain, outbred mice. This model will be an attractive tool to understand the biology of anti-hormonal breast cancer in women. PMID:25230850

  8. Changes in arterial blood pressure elicited by severe passive heating at rest is associated with hyperthermia-induced hyperventilation in humans.

    PubMed

    Fujii, Naoto; Ichinose, Masashi; Honda, Yasushi; Tsuji, Bun; Watanabe, Kazuhito; Kondo, Narihiko; Nishiyasu, Takeshi

    2013-01-01

    The arterial blood pressure and ventilatory responses to severe passive heating at rest varies greatly among individuals. We tested the hypothesis that the increase in ventilation seen during severe passive heating of resting humans is associated with a decrease in arterial blood pressure. Passive heating was performed on 18 healthy males using hot water immersion to the level of the iliac crest and a water-perfused suit. We then divided the subjects into two groups: MAP(NOTINC) (n = 8), whose mean arterial blood pressure (MAP) at the end of heating had increased by ≤3 mmHg, and MAP(INC) (n = 10), whose MAP increased by >3 mmHg. Increases in esophageal temperature (T (es)) elicited by the heating were similar in the two groups (+2.3 ± 0.3 vs. +2.4 ± 0.4 °C). Early during heating (increase in T (es) was <1.5 °C), MAP, minute ventilation ([Formula: see text]), and end-tidal CO(2) pressure ([Formula: see text]) were similar between the groups. However, during the latter part of heating (increase in T (es) was ≥1.5 °C), the increase in [Formula: see text] and decrease in [Formula: see text] were significantly greater or tended to be greater, while the increase in MAP was significantly smaller in MAP(NOTINC) than MAP(INC). Among all subjects, heating-induced changes in [Formula: see text] significantly and negatively correlated with heating-induced changes in MAP during the latter part of heating (r = -0.52 to -0.74, P < 0.05). These results suggest that, in resting humans, 25-50 % of the variation in the magnitude of the arterial blood pressure response to severe passive heating can be explained by the magnitude of hyperthermia-induced hyperventilation.

  9. The Nucleocapsid Protein of Rift Valley Fever Virus Is a Potent Human CD8+ T Cell Antigen and Elicits Memory Responses

    PubMed Central

    Xu, Weidong; Watts, Douglas M.; Costanzo, Margaret C.; Tang, Xiaolei; Venegas, Leon A.; Jiao, Feng; Sette, Alessandro; Sidney, John; Sewell, Andrew K.; Wooldridge, Linda; Makino, Shinji; Morrill, John C.; Peters, Clarence J.; Kan-Mitchell, June

    2013-01-01

    There is no licensed human vaccine currently available for Rift Valley Fever Virus (RVFV), a Category A high priority pathogen and a serious zoonotic threat. While neutralizing antibodies targeting the viral glycoproteins are protective, they appear late in the course of infection, and may not be induced in time to prevent a natural or bioterrorism-induced outbreak. Here we examined the immunogenicity of RVFV nucleocapsid (N) protein as a CD8+ T cell antigen with the potential for inducing rapid protection after vaccination. HLA-A*0201 (A2)-restricted epitopic determinants were identified with N-specific CD8+ T cells from eight healthy donors that were primed with dendritic cells transduced to express N, and subsequently expanded in vitro by weekly re-stimulations with monocytes pulsed with 59 15mer overlapping peptides (OLPs) across N. Two immunodominant epitopes, VT9 (VLSEWLPVT, N121–129) and IL9 (ILDAHSLYL, N165–173), were defined. VT9- and IL9-specific CD8+ T cells identified by tetramer staining were cytotoxic and polyfunctional, characteristics deemed important for viral control in vivo. These peptides induced specific CD8+ T cell responses in A2-transgenic mice, and more importantly, potent N-specific CD8+ T cell reactivities, including VT9- and IL9-specific ones, were mounted by mice after a booster vaccination with the live attenuated RVF MP-12. Our data suggest that the RVFV N protein is a potent human T cell immunogen capable of eliciting broad, immunodominant CD8+ T cell responses that are potentially protective. Understanding the immune responses to the nucleocapsid is central to the design of an effective RVFV vaccine irrespective of whether this viral protein is effective as a stand-alone immunogen or only in combination with other RVFV antigens. PMID:23527138

  10. Vaccine-Elicited V3 Loop-Specific Antibodies in Rhesus Monkeys and Control of a Simian-Human Immunodeficiency Virus Expressing a Primary Patient Human Immunodeficiency Virus Type 1 Isolate Envelope

    PubMed Central

    Letvin, Norman L.; Robinson, Suzanne; Rohne, Daniela; Axthelm, Michael K.; Fanton, John W.; Bilska, Miroslawa; Palker, Thomas J.; Liao, Hua-Xin; Haynes, Barton F.; Montefiori, David C.

    2001-01-01

    Vaccine-elicited antibodies specific for the third hypervariable domain of the surface gp120 of human immunodeficiency virus type 1 (HIV-1) (V3 loop) were assessed for their contribution to protection against infection in the simian-human immunodeficiency virus (SHIV)/rhesus monkey model. Peptide vaccine-elicited anti-V3 loop antibody responses were examined for their ability to contain replication of SHIV-89.6, a nonpathogenic SHIV expressing a primary patient isolate HIV-1 envelope, as well as SHIV-89.6P, a pathogenic variant of that virus. Low-titer neutralizing antibodies to SHIV-89.6 that provided partial protection against viremia following SHIV-89.6 infection were generated. A similarly low-titer neutralizing antibody response to SHIV-89.6P that did not contain viremia after infection with SHIV-89.6P was generated, but a trend toward protection against CD4+ T-lymphocyte loss was seen in these infected monkeys. These observations suggest that the V3 loop on some primary patient HIV-1 isolates may be a partially effective target for neutralizing antibodies induced by peptide immunogens. PMID:11287566

  11. Spontaneous retrograde migration of ureterovesical junction stone to the kidney; first ever reported case in the English literature in human.

    PubMed

    Khan, Ziauddin; Yaqoob, Alaeddin A; Bhatty, Tanweer A

    2016-01-01

    We present a case of spontaneous retrograde migration of ureterovesical junction stone to the kidney. A 26-year-old Bahraini male, diagnosed with left lower ureteric stone 7 months before this presentation. On his recent presentation, the stone has migrated down but not passed, confirmed on imaging. Operative removal was planned. X-ray kidney ureter bladder (KUB) in the morning of surgery did not reveal stone in the ureter, but the same shadow was seen in the kidney. An urgent computerized tomography-KUB was done, and this confirms the stone has migrated to the kidney. Surgery was canceled, and the stone was dealt with extracorporeal shockwave lithotripsy and was fragmented in the first session. This retrograde migration of lower ureteric stone to the kidney is not reported in the English literature in human before.

  12. Spontaneous cytotoxicity of human peripheral blood mononuclear cells for the lymphoblastoid cell line CCRF-CEM: augmentation by bacterial lipopolysaccharide.

    PubMed Central

    Schacter, B; Kleinhenz, M E; Edmonds, K; Ellner, J J

    1981-01-01

    Spontaneous cell-mediated cytotoxicity (SCMC) of human peripheral blood mononuclear cells for a poor target, CCRF-CEM, a lymphoblastoid cell line, was rapidly and markedly elevated by E. coli lipopolysaccharide (LPS). SCMC for K562, a myeloid cell line sensitive to SCMC, was only slightly elevated by LPS. The cytotoxicities of both adherent and non-adherent mononuclear cells for CCRF-CEM were elevated. A response to LPS was found in Fc gamma R-positive and Fc gamma R-negative T cells. LPS increased the binding of non-adherent cells to both targets, but analysis of the binding suggests that a subsequent step, either triggering of the cytotoxic mechanisms or susceptibility of the target was the basis for the increased SCMC. PMID:7039896

  13. Spontaneous retrograde migration of ureterovesical junction stone to the kidney; first ever reported case in the English literature in human.

    PubMed

    Khan, Ziauddin; Yaqoob, Alaeddin A; Bhatty, Tanweer A

    2016-01-01

    We present a case of spontaneous retrograde migration of ureterovesical junction stone to the kidney. A 26-year-old Bahraini male, diagnosed with left lower ureteric stone 7 months before this presentation. On his recent presentation, the stone has migrated down but not passed, confirmed on imaging. Operative removal was planned. X-ray kidney ureter bladder (KUB) in the morning of surgery did not reveal stone in the ureter, but the same shadow was seen in the kidney. An urgent computerized tomography-KUB was done, and this confirms the stone has migrated to the kidney. Surgery was canceled, and the stone was dealt with extracorporeal shockwave lithotripsy and was fragmented in the first session. This retrograde migration of lower ureteric stone to the kidney is not reported in the English literature in human before. PMID:27141199

  14. Spontaneous retrograde migration of ureterovesical junction stone to the kidney; first ever reported case in the English literature in human

    PubMed Central

    Khan, Ziauddin; Yaqoob, Alaeddin A.; Bhatty, Tanweer A.

    2016-01-01

    We present a case of spontaneous retrograde migration of ureterovesical junction stone to the kidney. A 26-year-old Bahraini male, diagnosed with left lower ureteric stone 7 months before this presentation. On his recent presentation, the stone has migrated down but not passed, confirmed on imaging. Operative removal was planned. X-ray kidney ureter bladder (KUB) in the morning of surgery did not reveal stone in the ureter, but the same shadow was seen in the kidney. An urgent computerized tomography-KUB was done, and this confirms the stone has migrated to the kidney. Surgery was canceled, and the stone was dealt with extracorporeal shockwave lithotripsy and was fragmented in the first session. This retrograde migration of lower ureteric stone to the kidney is not reported in the English literature in human before. PMID:27141199

  15. P2Y1 receptor activation elicits its partition out of membrane rafts and its rapid internalization from human blood vessels: implications for receptor signaling.

    PubMed

    Norambuena, Andrés; Poblete, M Inés; Donoso, M Verónica; Espinoza, C Sofía; González, Alfonso; Huidobro-Toro, J Pablo

    2008-12-01

    The nucleotide P2Y(1) receptor (P2Y(1)R) is expressed in both the endothelial and vascular smooth muscle cells; however, its plasma membrane microregionalization and internalization in human tissues remain unknown. We report on the role of membrane rafts in P2Y(1)R signaling by using sodium carbonate or OptiPrep sucrose density gradients, Western blot analysis, reduction of tissue cholesterol content, and vasomotor assays of endothelium-denuded human chorionic arteries. In tissue extracts prepared either in sodium carbonate or OptiPrep, approximately 20 to 30% of the total P2Y(1)R mass consistently partitioned into raft fractions and correlated with vasomotor activity. Vessel treatment with methyl beta-cyclodextrin reduced the raft partitioning of the P2Y(1)R and obliterated the P2Y(1)R-mediated contractions but not the vasomotor responses elicited by either serotonin or KCl. Perfusion of chorionic artery segments with 100 nM 2-methylthio ADP or 10 nM [[(1R,2R,3S,4R,5S)-4-[6-amino-2-(methylthio)-9H-purin-9-yl] 2,3dihydroxybicyclo[3.1.0]hex-1-yl]methyl] diphosphoric acid mono ester trisodium salt (MRS 2365), a selective P2Y(1)R agonist, not only displaced within 4 min the P2Y(1)R localization out of membrane rafts but also induced its subsequent internalization. 2'-Deoxy-N(6)-methyladenosine 3',5'-bisphosphate tetrasodium salt (MRS 2179), a specific P2Y(1)R antagonist, did not cause a similar displacement but blocked the agonist-induced exit from rafts. Neither adenosine nor uridine triphosphate displaced the P2Y(1)R from the membrane raft, further evidencing the pharmacodynamics of the receptor-ligand interaction. Vascular reactivity assays showed fading of the ligand-induced vasoconstrictions, a finding that correlated with the P2Y(1)R exit from raft domains and internalization. These results demonstrate in intact human vascular smooth muscle the association of the P2Y(1)R to membrane rafts, highlighting the role of this microdomain in P2Y(1)R signaling.

  16. Estimating the spontaneous mutation rate of loss of sex in the human pathogenic fungus Cryptococcus neoformans.

    PubMed Central

    Xu, Jianping

    2002-01-01

    Few events have evolutionary consequences as pervasive as changes in reproductive behavior. Among those changes, the loss of the ability to undergo sexual reproduction is probably the most profound. However, little is known about the rate of loss of sex. Here I describe an experimental system using the fungus Cryptococcus neoformans and provide the first empirical estimate of the spontaneous mutation rate of loss of sex in fungi. Two critical steps in sexual reproduction in C. neoformans were examined: mating and filamentation. Mating, the fusion of cells of opposite sexes, is a universal first step in eukaryotic sexual reproduction. In contrast, filamentation, a prerequisite process preceding meiosis and sexual spore development, is restricted to C. neoformans and a few other fungal species. After approximately 600 mitotic divisions under favorable asexual growth conditions, mean abilities for mating and filamentation decreased significantly by >67 and 24%, respectively. Similarly, though statistically not significant, the mean vegetative growth rates also decreased and among the mutation accumulation lines, the vegetative growth rates were negatively correlated to the mating ability. The estimated mutation rates to decreases in mating ability and filamentation were in excess of 0.0172 and 0.0036, respectively. The results show that C. neoformans can be a highly attractive model for analyses of reproductive system evolution in fungi. PMID:12454063

  17. Increased CD56(+) NK cells and enhanced Th1 responses in human unexplained recurrent spontaneous abortion.

    PubMed

    Gao, Y; Wang, P L

    2015-12-22

    Recurrent spontaneous abortion (RSA) is reported to be associated with immune imbalance at the maternal-fetal interface. Immune cells in the decidual tissue are involved in maintaining immune tolerance during pregnancy; however, whether natural killer (NK) and T cells are altered in unexplained RSA (URSA) remains unknown. In this study, we compared the number and percentage of CD56(+) NK cells, CD4(+) T cells and CD8(+) T cells by flow cytometry in 30 URSA patients and 30 normal pregnant controls. We found that there are a higher proportion of CD4(+) T cells and CD16(+)CD56(+) NK cells and a lower number of CD8(+) T cells in the decidual tissue of URSA patients compared to normal controls. In addition, the number of T helper type 1 (Th1) cells and the Th1/Th2 ratio were higher in URSA patients compared to normal pregnant controls. In conclusion, our results indicate that the changes in the proportion of local T lymphocyte subsets, NK and Th1 cells, in the maternal-fetal interface may be related to occurrence of URSA.

  18. A recombinant mimetics of the HIV-1 gp41 prehairpin fusion intermediate fused with human IgG Fc fragment elicits neutralizing antibody response in the vaccinated mice

    SciTech Connect

    Qi, Zhi; Pan, Chungen; Lu, Hong; Shui, Yuan; Li, Lin; Li, Xiaojuan; Xu, Xueqing; Liu, Shuwen; Jiang, Shibo

    2010-07-30

    Research highlights: {yields} One recombinant mimetics of gp41 prehairpin fusion intermediate (PFI) consisting of gp41 N46 sequence, foldon and IgG Fc, designated N46FdFc, was expressed. {yields} N46FdFc-induced antibodies in mice that neutralized HIV-1 infection, inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. {yields} These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines. -- Abstract: HIV-1 gp41 prehairpin fusion intermediate (PFI) composed of three N-terminal heptad repeats (NHR) plays a crucial role in viral fusion and entry and represents an attractive target for anti-HIV therapeutics (e.g., enfuvirtide) and vaccines. In present study, we constructed and expressed two recombinant gp41 PFI mimetics, designated N46Fd and N46FdFc. N46Fd consists of N46 (residues 536-581) in gp41 NHR and foldon (Fd), a trimerization motif. N46FdFc is composed of N46Fd fused with human IgG Fc fragment as an immunoenhancer. We immunized mice with N46 peptide, N46Fd and N46FdFc, respectively, and found that only N46FdFc elicited neutralizing antibody response in mice against infection by HIV-1 strains IIIB (clade B, X4), 92US657 (clade B, R5), and 94UG103 (clade A, X4R5). Anti-N46FdFc antibodies inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines.

  19. A Rapid Immunization Strategy with a Live-Attenuated Tetravalent Dengue Vaccine Elicits Protective Neutralizing Antibody Responses in Non-Human Primates

    PubMed Central

    Ambuel, Yuping; Young, Ginger; Brewoo, Joseph N.; Paykel, Joanna; Weisgrau, Kim L.; Rakasz, Eva G.; Haller, Aurelia A.; Royals, Michael; Huang, Claire Y.-H.; Capuano, Saverio; Stinchcomb, Dan T.; Partidos, Charalambos D.; Osorio, Jorge E.

    2014-01-01

    Dengue viruses (DENVs) cause approximately 390 million cases of DENV infections annually and over 3 billion people worldwide are at risk of infection. No dengue vaccine is currently available nor is there an antiviral therapy for DENV infections. We have developed a tetravalent live-attenuated DENV vaccine tetravalent dengue vaccine (TDV) that consists of a molecularly characterized attenuated DENV-2 strain (TDV-2) and three chimeric viruses containing the pre-membrane and envelope genes of DENV-1, -3, and -4 expressed in the context of the TDV-2 genome. To impact dengue vaccine delivery in endemic areas and immunize travelers, a simple and rapid immunization strategy (RIS) is preferred. We investigated RIS consisting of two full vaccine doses being administered subcutaneously or intradermally on the initial vaccination visit (day 0) at two different anatomical locations with a needle-free disposable syringe jet injection delivery devices (PharmaJet) in non-human primates. This vaccination strategy resulted in efficient priming and induction of neutralizing antibody responses to all four DENV serotypes comparable to those elicited by the traditional prime and boost (2 months later) vaccination schedule. In addition, the vaccine induced CD4+ and CD8+ T cells producing IFN-γ, IL-2, and TNF-α, and targeting the DENV-2 NS1, NS3, and NS5 proteins. Moreover, vaccine-specific T cells were cross-reactive with the non-structural NS3 and NS5 proteins of DENV-4. When animals were challenged with DENV-2 they were protected with no detectable viremia, and exhibited sterilizing immunity (no increase of neutralizing titers post-challenge). RIS could decrease vaccination visits and provide quick immune response to all four DENV serotypes. This strategy could increase vaccination compliance and would be especially advantageous for travelers into endemic areas. PMID:24926294

  20. Eliciting Sound Memories.

    PubMed

    Harris, Anna

    2015-11-01

    Sensory experiences are often considered triggers of memory, most famously a little French cake dipped in lime blossom tea. Sense memory can also be evoked in public history research through techniques of elicitation. In this article I reflect on different social science methods for eliciting sound memories such as the use of sonic prompts, emplaced interviewing, and sound walks. I include examples from my research on medical listening. The article considers the relevance of this work for the conduct of oral histories, arguing that such methods "break the frame," allowing room for collaborative research connections and insights into the otherwise unarticulatable.

  1. Spontaneous origin from human embryonic stem cells of liver cells displaying conjoint meso-endodermal phenotype with hepatic functions

    PubMed Central

    Bandi, Sriram; Cheng, Kang; Joseph, Brigid; Gupta, Sanjeev

    2012-01-01

    Understanding the identity of lineage-specific cells arising during manipulations of stem cells is necessary for developing their potential applications. For instance, replacement of crucial functions in organ failure by transplantation of suitable stem-cell-derived cells will be applicable to numerous disorders, but requires insights into the origin, function and fate of specific cell populations. We studied mechanisms by which the identity of differentiated cells arising from stem cells could be verified in the context of natural liver-specific stem cells and whether such differentiated cells could be effective for supporting the liver following cell therapy in a mouse model of drug-induced acute liver failure. By comparing the identity of naturally occurring fetal human liver stem cells, we found that cells arising in cultures of human embryonic stem cells (hESCs) recapitulated an early fetal stage of liver cells, which was characterized by conjoint meso-endoderm properties. Despite this fetal stage, hESC-derived cells could provide liver support with appropriate metabolic and ammonia-fixation functions, as well as cytoprotection, such that mice were rescued from acute liver failure. Therefore, spontaneous or induced differentiation of human embryonic stem cells along the hepatic endoderm will require transition through fetal-like stages. This offers opportunities to prospectively identify whether suitable cells have been generated through manipulation of stem cells for cell therapy and other applications. PMID:22349702

  2. Rosuvastatin ameliorates inflammation, renal fat accumulation, and kidney injury in transgenic spontaneously hypertensive rats expressing human C-reactive protein.

    PubMed

    Šilhavý, J; Zídek, V; Landa, V; Šimáková, M; Mlejnek, P; Oliyarnyk, O; Malínská, H; Kazdová, L; Mancini, M; Pravenec, M

    2015-01-01

    Recently, we derived "humanized" spontaneously hypertensive rats (SHR-CRP) in which transgenic expression of human CRP induces inflammation, oxidative stress, several features of metabolic syndrome and target organ injury. In addition, we found that rosuvastatin treatment of SHR-CRP transgenic rats can protect against pro-inflammatory effects of human CRP and also reduce cardiac inflammation and oxidative damage. In the current study, we tested the effects of rosuvastatin (5 mg/kg) on kidney injury in SHR-CRP males versus untreated SHR-CRP and SHR controls. All rats were fed a high sucrose diet. In SHR-CRP transgenic rats, treatment with rosuvastatin for 10 weeks, compared to untreated transgenic rats and SHR controls, was associated with significantly reduced systemic inflammation which was accompanied with activation of antioxidative enzymes in the kidney, lower renal fat accumulation, and with amelioration of histopathological changes in the kidney. These findings provide evidence that, in the presence of high CRP levels, rosuvastatin exhibits significant anti-inflammatory, anti-oxidative, and renoprotective effects.

  3. Some Studies of Spontaneous and Evoked Acoustic Emissions from the Human Ear.

    NASA Astrophysics Data System (ADS)

    Sutton, Graham John

    Available from UMI in association with The British Library. Several studies of spontaneous and evoked oto -acoustic emissions (SOAEs and EOAEs) and their relationship to normal and pathological hearing mechanisms are described. (1) A computer model was developed to study the theory that the EOAE is produced by summation of responses from activity distributed along the cochlea. It was found that, whilst with a regular cochlea and mapping the summed response is small owing to phase cancellation, any irregularity of mapping or structure or sensitivity gives rise to a sharply-tuned response showing many of the characteristics of EOAEs. (2) A search for SOAEs in 17 normal subjects revealed a prevalence of 53% (42% of ears), which was significantly higher among the females. (3) A group of 49 clinical tinnitus sufferers was investigated to test the hypothesis that SOAEs might be responsible in some cases. 3 such cases were found, all with tonal tinnitus and normal hearing at the tinnitus pitch (although 1 had a bilateral loss at other frequencies). The SOAEs in both studies were found between 680 and 9610 Hz at levels up to 24 dB SPL. They were not found at frequencies where hearing threshold was greater than 20 dB, and no consistent association with audiometric abnormalities was noted, implying that they should be seen as part of normal hearing variation, rather than the result of minor pathology. (4) Suppression effects were studied for (a) SOAEs in 2 ears and (b) both click -evoked and continuous-tone evoked OAEs in another ear. A number of features were observed, most notably multiple lobes in many of the suppression tuning curves. The implications of these results for theories of OAE generation are discussed.

  4. Spontaneous fatal Human herpesvirus 1 encephalitis in two domestic rabbits (Oryctolagus cuniculus).

    PubMed

    de Matos, Ricardo; Russell, Duncan; Van Alstine, William; Miller, Andrew

    2014-09-01

    Despite the particular susceptibility of the rabbit to experimental infection with Human herpesvirus 1 (HHV-1) and the high seroprevalence of HHV-1 in human beings, reports of natural infection in pet rabbits are rare. The current report describes 2 cases of HHV encephalitis in pet rabbits in North America. Antemortem clinical signs included seizures, ptyalism, and muscle tremors. Results of complete blood cell count and plasma biochemistry panel were unremarkable except for a mild leukocytosis in both cases. Both rabbits died after a short period of hospitalization. Rabbit 1 presented mild optic chiasm hemorrhage on gross examination, while rabbit 2 had no gross lesions. Histologic findings for both cases included lymphocytic and/or lymphoplasmacytic encephalitis with necrosis and the presence of intranuclear inclusion bodies in neurons and glial cells. Polymerase chain reaction (PCR) analysis of affected brain tissue using primers specific for Human herpesvirus 1 and 2 confirmed diagnosis of HHV encephalitis for rabbit 1. Immunohistochemical staining (poly- and monoclonal) and PCR analysis using primers specific to HHV-1 confirmed the diagnosis of HHV-1 encephalitis for rabbit 2. The owner of rabbit 2 was suspected to be the source of infection due to close contact during an episode of herpes labialis. Given the high susceptibility of rabbits to experimental HHV-1, high seroprevalence of HHV-1 in human beings, and severity of clinical disease in this species, clinician awareness and client education is important for disease prevention. Human herpesvirus 1 encephalitis should be considered as a differential diagnosis for rabbits with neurologic disease.

  5. Imaging of ultraweak spontaneous photon emission from human body displaying diurnal rhythm.

    PubMed

    Kobayashi, Masaki; Kikuchi, Daisuke; Okamura, Hitoshi

    2009-07-16

    The human body literally glimmers. The intensity of the light emitted by the body is 1000 times lower than the sensitivity of our naked eyes. Ultraweak photon emission is known as the energy released as light through the changes in energy metabolism. We successfully imaged the diurnal change of this ultraweak photon emission with an improved highly sensitive imaging system using cryogenic charge-coupled device (CCD) camera. We found that the human body directly and rhythmically emits light. The diurnal changes in photon emission might be linked to changes in energy metabolism.

  6. Fluorescent probes as a tool for cell population tracking in spontaneously active neural networks derived from human pluripotent stem cells.

    PubMed

    Mäkinen, M; Joki, T; Ylä-Outinen, L; Skottman, H; Narkilahti, S; Aänismaa, R

    2013-04-30

    Applications such as 3D cultures and tissue modelling require cell tracking with non-invasive methods. In this work, the suitability of two fluorescent probes, CellTracker, CT, and long chain carbocyanine dye, DiD, was investigated for long-term culturing of labeled human pluripotent stem cell-derived neural cells. We found that these dyes did not affect the cell viability. However, proliferation was decreased in DiD labeled cell population. With both dyes the labeling was stable up to 4 weeks. CT and DiD labeled cells could be co-cultured and, importantly, these mixed populations had their normal ability to form spontaneous electrical network activity. In conclusion, human neural cells can be successfully labeled with these two fluorescent probes without significantly affecting the cell characteristics. These labeled cells could be utilized further in e.g. building controlled neuronal networks for neurotoxicity screening platforms, combining cells with biomaterials for 3D studies, and graft development. PMID:23473797

  7. Assessment of myometrial transcriptome changes associated with spontaneous human labour by high-throughput RNA-seq.

    PubMed

    Chan, Yi-Wah; van den Berg, Hugo A; Moore, Jonathan D; Quenby, Siobhan; Blanks, Andrew M

    2014-03-01

    The transition of the human uterus from a quiescent to a contractile state takes place over a number of weeks. On such biological time scales, cellular phenotype is modified by changes in the transcriptome, which in turn is under the control of the underlying endocrine, paracrine, and biophysical processes resulting from the ongoing pregnancy. In this study, we characterize the transition of the human myometrial transcriptome at term from not in labour (NIL) to in labour (LAB) using high throughput RNA sequencing (RNA-seq). RNA was isolated from the myometrium of uterine biopsies from patients at term who were not in labour (n = 5) and at term in spontaneous labour (n = 5) without augmentation. A total of 143.6 million separate reads were sequenced, achieving, on average, ∼13 times coverage of the expressed human transcriptome per sample. Principal component analysis indicated that the NIL and LAB transcriptomes could be distinguished as two distinct clusters. A comparison of the NIL and LAB groups, using three different statistical approaches (baySeq, edgeR, and DESeq), demonstrated an overlap of 764 differentially expressed genes. A comparison with currently available microarray data revealed only a partial overlap in differentially expressed genes. We conclude that the described RNA-seq data sets represent the first fully annotated catalogue of expressed mRNAs in human myometrium. When considered together, the full expression repertoire and the differentially expressed gene sets should provide an excellent resource for formulating new hypotheses of physiological function, as well as the discovery of novel therapeutic targets.

  8. Plumbagin elicits differential proteomic responses mainly involving cell cycle, apoptosis, autophagy, and epithelial-to-mesenchymal transition pathways in human prostate cancer PC-3 and DU145 cells

    PubMed Central

    Qiu, Jia-Xuan; Zhou, Zhi-Wei; He, Zhi-Xu; Zhao, Ruan Jin; Zhang, Xueji; Yang, Lun; Zhou, Shu-Feng; Mao, Zong-Fu

    2015-01-01

    Plumbagin (PLB) has exhibited a potent anticancer effect in preclinical studies, but the molecular interactome remains elusive. This study aimed to compare the quantitative proteomic responses to PLB treatment in human prostate cancer PC-3 and DU145 cells using the approach of stable-isotope labeling by amino acids in cell culture (SILAC). The data were finally validated using Western blot assay. First, the bioinformatic analysis predicted that PLB could interact with 78 proteins that were involved in cell proliferation and apoptosis, immunity, and signal transduction. Our quantitative proteomic study using SILAC revealed that there were at least 1,225 and 267 proteins interacting with PLB and there were 341 and 107 signaling pathways and cellular functions potentially regulated by PLB in PC-3 and DU145 cells, respectively. These proteins and pathways played a critical role in the regulation of cell cycle, apoptosis, autophagy, epithelial to mesenchymal transition (EMT), and reactive oxygen species generation. The proteomic study showed substantial differences in response to PLB treatment between PC-3 and DU145 cells. PLB treatment significantly modulated the expression of critical proteins that regulate cell cycle, apoptosis, and EMT signaling pathways in PC-3 cells but not in DU145 cells. Consistently, our Western blotting analysis validated the bioinformatic and proteomic data and confirmed the modulating effects of PLB on important proteins that regulated cell cycle, apoptosis, autophagy, and EMT in PC-3 and DU145 cells. The data from the Western blot assay could not display significant differences between PC-3 and DU145 cells. These findings indicate that PLB elicits different proteomic responses in PC-3 and DU145 cells involving proteins and pathways that regulate cell cycle, apoptosis, autophagy, reactive oxygen species production, and antioxidation/oxidation homeostasis. This is the first systematic study with integrated computational, proteomic, and

  9. Cross-neutralizing antibodies elicited by the Cervarix® human papillomavirus vaccine display a range of Alpha-9 inter-type specificities.

    PubMed

    Bissett, Sara L; Draper, Eve; Myers, Richard E; Godi, Anna; Beddows, Simon

    2014-02-26

    The highly efficacious human papillomavirus (HPV) vaccines contain virus-like particles (VLP) representing genotypes HPV16 and HPV18, which together account for approximately 70% of cervical cancer cases. Vaccine-type protection is thought to be mediated by high titer, type-specific neutralizing antibodies. The vaccines also confer a degree of cross-protection against some genetically-related types from the Alpha-9 (HPV16-like: HPV31, HPV33, HPV35, HPV52, HPV58) and Alpha-7 (HPV18-like: HPV39, HPV45, HPV59, HPV68) species groups. Cross-protection is coincident with the detection of low titer serum responses against non-vaccine types by vaccinees. Such antibodies may be the effectors of cross-protection or their detection may be useful as a correlate or surrogate. This study evaluated whether cross-neutralization of HPV types from the Alpha-9 species group is mediated by antibodies with a predominantly type-restricted specificity for HPV16 that nevertheless exhibit low affinity interactions with non-vaccine types, or by antibody specificities that demonstrate similar recognition of vaccine and non-vaccine types but are present at very low levels. Antibodies generated following Cervarix® vaccination of 13-14 year old girls were evaluated by pseudovirus neutralization, VLP ELISA and by enrichment of target antigen specificity using VLP-immobilized beads. Two-dimensional hierarchical clustering of serology data demonstrated that the antibody specificity profile generated by VLP ELISA was both quantitatively and qualitatively different from the neutralizing antibody specificity profile. Target-specific antibody enrichment demonstrated that cross-neutralization of non-vaccine types was due to a minority of antibodies rather than by the weak interactions of a predominantly type-restricted HPV16 antibody specificity. Furthermore, cross-neutralization of non-vaccine types appeared to be mediated by multiple antibody specificities, recognizing single and multiple non

  10. The Elicited Language Inventory and the Influence of Contextual Cues.

    ERIC Educational Resources Information Center

    Nelson, Lauren K.; Weber-Olsen, Marcia

    1980-01-01

    The Elicited Language Inventory (ELI) was administered in standardized fashion and in a modified procedure with contextually supported cues and grammatical morpheme use under the two ELI presentation conditions was compared with use of the same morphemes in spontaneous speech. Results favored modified use of the ELI with contextually cued items…

  11. Characterization of the tissue-level Ca2+ signals in spontaneously contracting human myometrium

    PubMed Central

    Bru-Mercier, Gilles; Gullam, Joanna E; Thornton, Steven; Blanks, Andrew M; Shmygol, Anatoly

    2012-01-01

    In the labouring uterus, millions of myocytes forming the complex geometrical structure of myometrium contract in synchrony to increase intrauterine pressure, dilate the cervix and eventually expel the foetus through the birth canal. The mechanisms underlying the precise coordination of contractions in human myometrium are not completely understood. In the present study, we have characterized the spatio-temporal properties of tissue-level [Ca2+]i transients in thin slices of intact human myometrium. We found that the waveform of [Ca2+]i transients and isotonic contractions recorded from thin slices was similar to the waveform of isometric contractions recorded from the larger strips in traditional organ bath experiments, suggesting that the spatio-temporal information obtained from thin slices is representative of the whole tissue. By comparing the time course of [Ca2+]i transients in individual cells to that recorded from the bundles of myocytes we found that the majority of myocytes produce rapidly propagating long-lasting [Ca2+]i transients accompanied by contractions. We also found a small number of cells showing desynchronized [Ca2+]i oscillations that did not trigger contractions. The [Ca2+]i oscillations in these cells were insensitive to nifedipine, but readily inhibited by the T-type Ca2+ channel inhibitor NNC55-0396. In conclusion, our data suggest that the spread of [Ca2+]i signals in human myometrium is achieved via propagation of long-lasting action potentials. The propagation was fast when action potentials propagated along bundles of myocytes and slower when propagating between the bundles of uterine myocytes. PMID:22947266

  12. Elicitation of Slips of the Tongue from Young Children: A New Method and Preliminary Observations.

    ERIC Educational Resources Information Center

    Smith, Bruce L.

    1990-01-01

    Examination of the use of short "tongue-twister" phrases in eliciting spontaneous slips of the tongue in five year olds indicated that the technique was a feasible and beneficial method for collecting spoonerism data from children. (24 references) (CB)

  13. Molecular features of a human rhabdomyosarcoma cell line with spontaneous metastatic progression

    PubMed Central

    Scholl, F A; Betts, D R; Niggli, F K; Schäfer, B W

    2000-01-01

    A novel human cell line was established from a primary botryoid rhabdomyosarcoma. Reverse transcription polymerase chain reaction investigations of this cell line, called RUCH-2, demonstrated expression of the regulatory factors PAX3, Myf3 and Myf5. After 3.5 months in culture, cells underwent a crisis after which Myf3 and Myf5 could no longer be detected, whereas PAX3 expression remained constant over the entire period. Karyotype analysis revealed breakpoints in regions similar to previously described alterations in primary rhabdomyosarcoma tumour samples. Interestingly, cells progressed to a metastatic phenotype, as observed by enhanced invasiveness in vitro and tumour growth in nude mice in vivo. On the molecular level, microarray analysis before and after progression identified extensive changes in the composition of the extracellular matrix. As expected, down-regulation of tissue inhibitors of metalloproteinases and up-regulation of matrix metalloproteinases were observed. Extensive down-regulation of several death receptors of the tumour necrosis factor family suggests that these cells might have an altered response to appropriate apoptotic stimuli. The RUCH-2 cell line represents a cellular model to study multistep tumorigenesis in human rhabdomyosarcoma, allowing molecular comparison of tumorigenic versus metastatic cancer cells. © 2000 Cancer Research Campaign PMID:10735512

  14. Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes

    NASA Technical Reports Server (NTRS)

    Romanov, S. R.; Kozakiewicz, B. K.; Holst, C. R.; Stampfer, M. R.; Haupt, L. M.; Tlsty, T. D.

    2001-01-01

    Senescence and genomic integrity are thought to be important barriers in the development of malignant lesions. Human fibroblasts undergo a limited number of cell divisions before entering an irreversible arrest, called senescence. Here we show that human mammary epithelial cells (HMECs) do not conform to this paradigm of senescence. In contrast to fibroblasts, HMECs exhibit an initial growth phase that is followed by a transient growth plateau (termed selection or M0; refs 3-5), from which proliferative cells emerge to undergo further population doublings (approximately 20-70), before entering a second growth plateau (previously termed senescence or M1; refs 4-6). We find that the first growth plateau exhibits characteristics of senescence but is not an insurmountable barrier to further growth. HMECs emerge from senescence, exhibit eroding telomeric sequences and ultimately enter telomere-based crisis to generate the types of chromosomal abnormalities seen in the earliest lesions of breast cancer. Growth past senescent barriers may be a pivotal event in the earliest steps of carcinogenesis, providing many genetic changes that predicate oncogenic evolution. The differences between epithelial cells and fibroblasts provide new insights into the mechanistic basis of neoplastic transformation.

  15. Spontaneous Fission

    DOE R&D Accomplishments Database

    Segre, Emilio

    1950-11-22

    The first attempt to discover spontaneous fission in uranium was made by [Willard] Libby, who, however, failed to detect it on account of the smallness of effect. In 1940, [K. A.] Petrzhak and [G. N.] Flerov, using more sensitive methods, discovered spontaneous fission in uranium and gave some rough estimates of the spontaneous fission decay constant of this substance. Subsequently, extensive experimental work on the subject has been performed by several investigators and will be quoted in the various sections. [N.] Bohr and [A.] Wheeler have given a theory of the effect based on the usual ideas of penetration of potential barriers. On this project spontaneous fission has been studied for the past several years in an effort to obtain a complete picture of the phenomenon. For this purpose the spontaneous fission decay constants {lambda} have been measured for separated isotopes of the heavy elements wherever possible. Moreover, the number {nu} of neutrons emitted per fission has been measured wherever feasible, and other characteristics of the spontaneous fission process have been studied. This report summarizes the spontaneous fission work done at Los Alamos up to January 1, 1945. A chronological record of the work is contained in the Los Alamos monthly reports.

  16. [HUMAN CYTOMEGALOVIRUS INFECTION AND SPONTANEOUS ABORTION IN PREGNANT WOMEN OF I AND II TRIMESTER].

    PubMed

    Cheshik, S G; Kisteneva, L B

    2016-01-01

    The goal of this work was the evaluation of the frequency of human CMV infection among the women, whose pregnancy ended in miscarriage, detection of active forms of infection and treatment before pregnancy. Virological and sero-immunological techniques were used. A total of 116 women who had miscarriages before the 28 week of pregnancy were submitted to the CMV test. 109 women (94.0%) demonstrated positive results. 49 women (42.2%) had active form of the cytomegalovirus infection. 13 women (26.5%) had the recurrent form and 36 patients (73.5%) had the persistent form of CMV infection (stage of productive replication). All the women with active CMVI were treated before the next pregnancy. Immunomodulatory therapy for the treatment was used. PMID:27451499

  17. The ictal wavefront is the spatiotemporal source of discharges during spontaneous human seizures

    PubMed Central

    Smith, Elliot H.; Liou, Jyun-you; Davis, Tyler S.; Merricks, Edward M.; Kellis, Spencer S.; Weiss, Shennan A.; Greger, Bradley; House, Paul A.; McKhann II, Guy M.; Goodman, Robert R.; Emerson, Ronald G.; Bateman, Lisa M.; Trevelyan, Andrew J.; Schevon, Catherine A.

    2016-01-01

    The extensive distribution and simultaneous termination of seizures across cortical areas has led to the hypothesis that seizures are caused by large-scale coordinated networks spanning these areas. This view, however, is difficult to reconcile with most proposed mechanisms of seizure spread and termination, which operate on a cellular scale. We hypothesize that seizures evolve into self-organized structures wherein a small seizing territory projects high-intensity electrical signals over a broad cortical area. Here we investigate human seizures on both small and large electrophysiological scales. We show that the migrating edge of the seizing territory is the source of travelling waves of synaptic activity into adjacent cortical areas. As the seizure progresses, slow dynamics in induced activity from these waves indicate a weakening and eventual failure of their source. These observations support a parsimonious theory for how large-scale evolution and termination of seizures are driven from a small, migrating cortical area. PMID:27020798

  18. [HUMAN CYTOMEGALOVIRUS INFECTION AND SPONTANEOUS ABORTION IN PREGNANT WOMEN OF I AND II TRIMESTER].

    PubMed

    Cheshik, S G; Kisteneva, L B

    2016-01-01

    The goal of this work was the evaluation of the frequency of human CMV infection among the women, whose pregnancy ended in miscarriage, detection of active forms of infection and treatment before pregnancy. Virological and sero-immunological techniques were used. A total of 116 women who had miscarriages before the 28 week of pregnancy were submitted to the CMV test. 109 women (94.0%) demonstrated positive results. 49 women (42.2%) had active form of the cytomegalovirus infection. 13 women (26.5%) had the recurrent form and 36 patients (73.5%) had the persistent form of CMV infection (stage of productive replication). All the women with active CMVI were treated before the next pregnancy. Immunomodulatory therapy for the treatment was used.

  19. A new non-invasive statistical method to assess the spontaneous cardiac baroreflex in humans.

    PubMed

    Ducher, M; Fauvel, J P; Gustin, M P; Cerutti, C; Najem, R; Cuisinaud, G; Laville, M; Pozet, N; Paultre, C Z

    1995-06-01

    1. A new method was developed to evaluate cardiac baroreflex sensitivity. The association of a high systolic blood pressure with a low heart rate or the converse is considered to be under the influence of cardiac baroreflex activity. This method is based on the determination of the statistical dependence between systolic blood pressure and heart rate values obtained non-invasively by a Finapres device. Our computerized analysis selects the associations with the highest statistical dependence. A 'Z-coefficient' quantifies the strength of the statistical dependence. The slope of the linear regression, computed on these selected associations, is used to estimate baroreflex sensitivity. 2. The present study was carried out in 11 healthy resting male subjects. The results obtained by the 'Z-coefficient' method were compared with those obtained by cross-spectrum analysis, which has already been validated in humans. Furthermore, the reproducibility of both methods was checked after 1 week. 3. The results obtained by the two methods were significantly correlated (r = 0.78 for the first and r = 0.76 for the second experiment, P < 0.01). When repeated after 1 week, the average results were not significantly different. Considering individual results, test-retest correlation coefficients were higher with the Z-analysis (r = 0.79, P < 0.01) than with the cross-spectrum analysis (r = 0.61, P < 0.05). 4. In conclusion, as the Z-method gives results similar to but more reproducible than the cross-spectrum method, it might be a powerful and reliable tool to assess baroreflex sensitivity in humans.

  20. Spontaneous transfer of stearic acids between human serum albumin and PEG:2000-grafted DPPC membranes.

    PubMed

    Pantusa, Manuela; Stirpe, Andrea; Sportelli, Luigi; Bartucci, Rosa

    2010-05-01

    Electron spin resonance (ESR) spectroscopy is used to study the transfer of stearic acids between human serum albumin (HSA) and sterically stabilized liposomes (SSL) composed of dipalmitoylphosphatidylcholine (DPPC) and of submicellar content of poly(ethylene glycol:2000)-dipalmitoylphosphatidylethanolamine (PEG:2000-DPPE). Protein/lipid dispersions are considered in which spin-labelled stearic acids at the 16th carbon atom along the acyl chain (16-SASL) are inserted either in the protein or in the SSL. Two component ESR spectra with different rotational mobility are obtained over a broad range of temperature and membrane composition. Indeed, superimposed to an anisotropic protein-signal, appears a more isotropic lipid-signal. Since in the samples only one matrix (protein or membranes) is spin-labelled, the other component accounts for the transfer of 16-SASL between albumin and membranes. The two components have been resolved and quantified by spectral subtractions, and the fraction, f (p) (16-SASL), of spin labels bound non-covalently to the protein has been used to monitor the transfer. It is found that it depends on the type of donor and acceptor matrix, on the physical state of the membranes and on the grafting density of the polymer-lipids. Indeed, it is favoured from SSL to HSA and the fraction of stearic acids transferred increases with temperature in both directions of transfer. Moreover, in the presence of polymer-lipids, the transfer from HSA to SSL is slightly attenuated, especially in the brush regime of the polymer-chains. Instead, the transfer from SSL to HSA is favoured by the polymer-lipids much more in the mushroom than in the brush regime. PMID:19350232

  1. Radiosensitivity of human squamous carcinoma cell lines is associated with amount of spontaneous DNA strand breaks.

    PubMed

    Polischouk, A G; Grénman, R; Granath, F; Lewensohn, R

    2001-01-01

    We asked whether the constitutive level of DNA strand breaks (SBs) in four human squamous carcinoma cell lines is associated with their radiosensitivity, measured by the clonogenic assay. Because impairment in DNA replication and the action of endogenous deoxyribonucleases are two major sources of DNA strand breaks under normal cell metabolism, we also analyzed DNA polymerase and DNA ligase activities as well as the functional status of Poly(ADP-ribose) polymerase (PARP) and nucleolytic degradation of genomic DNA. We showed that the two relatively radioresistant cell lines, UM-SCC-1 and UT-SCC-5, had a statistically significant lower constitutive level of DNA SBs, as measured by DNA precipitation technique, compared with the two relatively radiosensitive cell lines, UM-SCC-14A and UT-SCC-9. We found that cell lines with a higher level of broken DNA tended to have a higher constitutive level of DNA polymerase alpha activity, measured by incorporation of [(3)H]dTTP in DNase I-activated DNA. UM-SCC-1, UT-SCC-5, and UM-SCC-14A did not show any difference in DNA ligase activity when a nicked oligonucleotide was used as substrate. The most radiosensitive cell line, UT-SCC-9, had a significantly lower ligation efficiency compared to the other three cell lines. The functional status of the PARP was the same in the four cell lines. Although none of the four cell lines showed a characteristic apoptotic or necrotic degradation of genomic DNA, when tested with the "plasmid rejoining assay," a significant degradation of the plasmid DNA in UT-SCC-9 was detected. We conclude that the high fraction of DNA SBs for UT-SCC-9, the most radiosensitive cell line, is most likely a consequence of low ligation efficiency combined with a relatively high DNA polymerase alpha activity and the nuclease degradation of DNA. PMID:11992385

  2. The Use of Elicited Imitation in Second Language Acquisition Research. Working Papers on Bilingualism, No. 2.

    ERIC Educational Resources Information Center

    Naiman, Neil

    This paper reports on a study undertaken to investigate the relationship between elicited imitation data and comprehension data, as measured by a picture-identification task and a second language (L2) to first language (L1) translation task, and between elicited imitation data and production data, as measured by a spontaneous production task and…

  3. Spontaneous production of thymocyte-activating factor by human gingival fibroblasts and its autoregulatory effect on their proliferation.

    PubMed Central

    Ohmori, Y; Hanazawa, S; Amano, S; Miyoshi, T; Hirose, K; Kitano, S

    1987-01-01

    The purpose of this study was to examine whether human gingival fibroblasts produce a cytokine which modulates in immune and inflammatory responses including alterations in connective tissue metabolism in periodontal tissue. We found that a cultured human gingival fibroblast cell line (Gin-1) and freshly isolated human gingival fibroblasts produced thymocyte-activating factor(s), so we called the factor(s) fibroblast-derived thymocyte-activating factor (FTAF). Growth of the producing cell was itself modulated by the factor(s). Gin-1 cells spontaneously produced a significant amount of FTAF in a cell growth-dependent manner. Maximum activity was observed in conditioned medium from stationary-phase cells. The activity in conditioned medium of cultures lacking serum was significantly higher than that in those containing serum. Treatment of Gin-1 cell cultures with cycloheximide, an inhibitor of protein synthesis, markedly inhibited FTAF production. When Gin-1 cells were stimulated by triggering with muramyl dipeptide or sonicated extracts of Bacteroides gingivalis, FTAF production was significantly stimulated. Freshly isolated human gingival fibroblasts from gingival biopsies of healthy donors also produced FTAF which enhanced thymocyte proliferation. Peaks of thymocyte proliferation activity in conditioned medium from Gin-1 cells were observed in fractions having molecular weights of 25,000, 35,000, and 45,000, as determined by Sephadex G-75 column chromatography. The peak fractions (partially purified FTAF) significantly suppressed the proliferation of Gin-1 cells themselves as evaluated by [3H]thymidine uptake. The suppressive effect of partially purified FTAF was, at least partially, mediated by endogenous prostaglandin for the following reasons: addition of indomethacin, and inhibitor of prostaglandin synthesis, abrogated the suppressive effect; partially purified FTAF stimulated the production of prostaglandin E2 by the cells; and the suppression of cell

  4. Effects of Metformin on Tissue Oxidative and Dicarbonyl Stress in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein.

    PubMed

    Malínská, Hana; Oliyarnyk, Olena; Škop, Vojtěch; Šilhavý, Jan; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Strnad, Hynek; Kazdová, Ludmila; Pravenec, Michal

    2016-01-01

    Inflammation and oxidative and dicarbonyl stress play important roles in the pathogenesis of type 2 diabetes. Metformin is the first-line drug of choice for the treatment of type 2 diabetes because it effectively suppresses gluconeogenesis in the liver. However, its "pleiotropic" effects remain controversial. In the current study, we tested the effects of metformin on inflammation, oxidative and dicarbonyl stress in an animal model of inflammation and metabolic syndrome, using spontaneously hypertensive rats that transgenically express human C-reactive protein (SHR-CRP). We treated 8-month-old male transgenic SHR-CRP rats with metformin (5 mg/kg/day) mixed as part of a standard diet for 4 weeks. A corresponding untreated control group of male transgenic SHR-CRP rats were fed a standard diet without metformin. In a similar fashion, we studied a group of nontransgenic SHR treated with metformin and an untreated group of nontransgenic SHR controls. In each group, we studied 6 animals. Parameters of glucose and lipid metabolism and oxidative and dicarbonyl stress were measured using standard methods. Gene expression profiles were determined using Affymetrix GeneChip Arrays. Statistical significance was evaluated by two-way ANOVA. In the SHR-CRP transgenic strain, we found that metformin treatment decreased circulating levels of inflammatory response marker IL-6, TNFα and MCP-1 while levels of human CRP remained unchanged. Metformin significantly reduced oxidative stress (levels of conjugated dienes and TBARS) and dicarbonyl stress (levels of methylglyoxal) in left ventricles, but not in kidneys. No significant effects of metformin on oxidative and dicarbonyl stress were observed in SHR controls. In addition, metformin treatment reduced adipose tissue lipolysis associated with human CRP. Possible molecular mechanisms of metformin action-studied by gene expression profiling in the liver-revealed deregulated genes from inflammatory and insulin signaling, AMP

  5. Effects of Metformin on Tissue Oxidative and Dicarbonyl Stress in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein

    PubMed Central

    Malínská, Hana; Oliyarnyk, Olena; Škop, Vojtěch; Šilhavý, Jan; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Strnad, Hynek; Kazdová, Ludmila; Pravenec, Michal

    2016-01-01

    Inflammation and oxidative and dicarbonyl stress play important roles in the pathogenesis of type 2 diabetes. Metformin is the first-line drug of choice for the treatment of type 2 diabetes because it effectively suppresses gluconeogenesis in the liver. However, its “pleiotropic” effects remain controversial. In the current study, we tested the effects of metformin on inflammation, oxidative and dicarbonyl stress in an animal model of inflammation and metabolic syndrome, using spontaneously hypertensive rats that transgenically express human C-reactive protein (SHR-CRP). We treated 8-month-old male transgenic SHR-CRP rats with metformin (5 mg/kg/day) mixed as part of a standard diet for 4 weeks. A corresponding untreated control group of male transgenic SHR-CRP rats were fed a standard diet without metformin. In a similar fashion, we studied a group of nontransgenic SHR treated with metformin and an untreated group of nontransgenic SHR controls. In each group, we studied 6 animals. Parameters of glucose and lipid metabolism and oxidative and dicarbonyl stress were measured using standard methods. Gene expression profiles were determined using Affymetrix GeneChip Arrays. Statistical significance was evaluated by two-way ANOVA. In the SHR-CRP transgenic strain, we found that metformin treatment decreased circulating levels of inflammatory response marker IL-6, TNFα and MCP-1 while levels of human CRP remained unchanged. Metformin significantly reduced oxidative stress (levels of conjugated dienes and TBARS) and dicarbonyl stress (levels of methylglyoxal) in left ventricles, but not in kidneys. No significant effects of metformin on oxidative and dicarbonyl stress were observed in SHR controls. In addition, metformin treatment reduced adipose tissue lipolysis associated with human CRP. Possible molecular mechanisms of metformin action–studied by gene expression profiling in the liver–revealed deregulated genes from inflammatory and insulin signaling, AMP

  6. Detection of cytomegalovirus, human parvovirus B19, and herpes simplex virus-1/2 in women with first-trimester spontaneous abortions.

    PubMed

    Zhou, Ya; Bian, Guohui; Zhou, Qiongxiu; Gao, Zhan; Liao, Pu; Liu, Yu; He, Miao

    2015-10-01

    The relationship between viral infections and first-trimester spontaneous abortions is not well-understood. The study aim was to investigate the prevalence of cytomegalovirus (CMV), human parvovirus B19 (B19V), and herpes simplex virus-1/2 (HSV-1/2) infection by molecular and serological techniques in women experiencing spontaneous miscarriage in the first trimester of pregnancy. Plasma samples were examined for CMV, B19V, and HSV-1/2 DNA using real-time quantitative polymerase chain reaction (Real-time qPCR), and for specific IgG antibodies against B19V, CMV, and HSV-1/2 using serological assays. The abortion group consisted of women (n = 1,716) with a history of two or more first-trimester spontaneous abortions. Women younger than 30 years possess higher portion to experience spontaneous abortion. No specimens were positive for B19V or CMV DNA. Seven out of the 1,716 specimens were positive for HSV-1/2 DNA. By serology, 47.24% of patients were positive for B19V IgG, 39.66% for HSV IgG, 79.31% for CMV IgG, and 9.31% for B19V IgM. The high rate of positivity for CMV IgG suggests that the majority of women with first-trimester spontaneous abortions are not susceptible to primary CMV infection. The lack of virus DNA in the majority of cases indicates that B19V, CMV, and HSV-1/2 infection is not commonly associated with first-trimester spontaneous abortion.

  7. Disruption of the p53-mediated G{sub 1}/S cell cycle checkpoint results in elevated rates of spontaneous genetic recombination in human fibroblasts

    SciTech Connect

    Strasfeld, L.; Brainerd, E.; Meyn, M.S.

    1994-09-01

    A key feature of the cancer-prone inherited disease ataxia-telangiectasia (A-T) is genetic instability. We recently demonstrated that one aspect of genetic instability in A-T is a marked elevation in the spontaneous rates of intrachromosomal mitotic recombination. We have proposed a model for A-T that attributes these high recombination rates to a lack of DNA damage-sensitive cell cycle checkpoints. One prediction of this model is that disrupting p53 function in normal cells should increase their spontaneous rates of recombination by interfering with their p53-dependent G{sub 1}/S cell cycle checkpoint. To test this prediction, we transfected control and A-T fibroblast lines that each harbor a single integrated copy of lacZ-based recombination vector (pLrec) with derivatives of a eukaryotic expression vector (pRep5) that contain either a dominant-negative p53 mutant (143{sup val{yields}ala}) or a human papilloma virus E6 gene (HPV18 E6). Expression of either of these genes results in loss of p53 function and abolition of the G{sub 1}/S cell cycle checkpoint. Four independent p53{sup 143ala} transformants of the control line showed 25-80 fold elevations in spontaneous recombination rates when compared to their parent cell line. Elevations in spontaneous recombination rates were also detected following transfection with the HPV18 E6 gene. In contrast, four independent p53{sup 143ala} transformants of the A-T cell line showed no significant changes in their already high spontaneous recombination rates. We are now extending these observations to additional normal human fibroblast lines and carrying out molecular analyses of the products of these recombinational events. Our results support our hypothesis that the lack of a p53-dependent G{sub 1}/S cell cycle checkpoint contributes to the hyperrecombination seen in A-T.

  8. Antibody-targeted NY-ESO-1 to mannose receptor or DEC-205 in vitro elicits dual human CD8+ and CD4+ T cell responses with broad antigen specificity.

    PubMed

    Tsuji, Takemasa; Matsuzaki, Junko; Kelly, Marcus P; Ramakrishna, Venky; Vitale, Laura; He, Li-Zhen; Keler, Tibor; Odunsi, Kunle; Old, Lloyd J; Ritter, Gerd; Gnjatic, Sacha

    2011-01-15

    Immunization of cancer patients with vaccines containing full-length tumor Ags aims to elicit specific Abs and both CD4(+) and CD8(+) T cells. Vaccination with protein Ags, however, often elicits only CD4(+) T cell responses without inducing Ag-specific CD8(+) T cells, as exogenous protein is primarily presented to CD4(+) T cells. Recent data revealed that Ab-mediated targeting of protein Ags to cell surface receptors on dendritic cells could enhance the induction of both CD4(+) and CD8(+) T cells. We investigated in this study if these observations were applicable to NY-ESO-1, a cancer-testis Ag widely used in clinical cancer vaccine trials. We generated two novel targeting proteins consisting of the full-length NY-ESO-1 fused to the C terminus of two human mAbs against the human mannose receptor and DEC-205, both internalizing molecules expressed on APC. These targeting proteins were evaluated for their ability to activate NY-ESO-1-specific human CD4(+) and CD8(+) T cells in vitro. Both targeted NY-ESO-1 proteins rapidly bound to their respective targets on APC. Whereas nontargeted and Ab-targeted NY-ESO-1 proteins similarly activated CD4(+) T cells, cross-presentation to CD8(+) T cells was only efficiently induced by targeted NY-ESO-1. In addition, both mannose receptor and DEC-205 targeting elicited specific CD4(+) and CD8(+) T cells from PBLs of cancer patients. Receptor-specific delivery of NY-ESO-1 to APC appears to be a promising vaccination strategy to efficiently generate integrated and broad Ag-specific immune responses against NY-ESO-1 in cancer patients.

  9. Freeze or Flee? Negative Stimuli Elicit Selective Responding

    ERIC Educational Resources Information Center

    Estes, Zachary; Verges, Michelle

    2008-01-01

    Humans preferentially attend to negative stimuli. A consequence of this automatic vigilance for negative valence is that negative words elicit slower responses than neutral or positive words on a host of cognitive tasks. Some researchers have speculated that negative stimuli elicit a general suppression of motor activity, akin to the freezing…

  10. Spontaneous Recovery

    ERIC Educational Resources Information Center

    Rescorla, Robert A.

    2004-01-01

    Spontaneous recovery from extinction is one of the most basic phenomena of Pavlovian conditioning. Although it can be studied by using a variety of designs, some procedures are better than others for identifying the involvement of underlying learning processes. A wide range of different learning mechanisms has been suggested as being engaged by…

  11. Trans-complementation by human apurinic endonuclease (Ape) of hypersensitivity to DNA damage and spontaneous mutator phenotype in apn1-yeast.

    PubMed Central

    Wilson, D M; Bennett, R A; Marquis, J C; Ansari, P; Demple, B

    1995-01-01

    Abasic (AP) sites in DNA are potentially lethal and mutagenic. 'Class II' AP endonucleases initiate the repair of these and other DNA lesions. In yeast, the predominant enzyme of this type is Apn1, and its elimination sensitizes the cells to killing by simple alkylating agents or oxidants, and raises the rate of spontaneous mutation. We investigated the ability of the major human class II AP endonuclease, Ape, which is structurally unrelated to Apn1, to replace the yeast enzyme in vivo. Confocal immunomicroscopy studies indicate that approximately 25% of the Ape expressed in yeast is present in the nucleus. High-level Ape expression corresponding to approximately 7000 molecules per nucleus, equal to the normal Apn1 copy number, restored resistance to methyl methanesulfonate to near wild-type levels in Apn1-deficient (apn1-) yeast. Ape expression in apn1- yeast provided little protection against H2O2 challenges, consistent with the weak 3'-repair diesterase activity of the human enzyme. Ape expression at approximately 2000 molecules per nucleus reduced the spontaneous mutation rate of apn1- yeast to that seen for wild-type cells. Because Ape has a powerful AP endonuclease but weak 3'-diesterase activity, these findings indicate that endogenously generated AP sites can drive spontaneous mutagenesis. Images PMID:8559661

  12. Unconsciously elicited perceptual prior

    PubMed Central

    Chang, Raymond; Baria, Alexis T.; Flounders, Matthew W.; He, Biyu J.

    2016-01-01

    Increasing evidence over the past decade suggests that vision is not simply a passive, feed-forward process in which cortical areas relay progressively more abstract information to those higher up in the visual hierarchy, but rather an inferential process with top-down processes actively guiding and shaping perception. However, one major question that persists is whether such processes can be influenced by unconsciously perceived stimuli. Recent psychophysics and neuroimaging studies have revealed that while consciously perceived stimuli elicit stronger responses in higher visual and frontoparietal areas than those that fail to reach conscious awareness, the latter can still drive high-level brain and behavioral responses. We investigated whether unconscious processing of a masked natural image could facilitate subsequent conscious recognition of its degraded counterpart (a black-and-white “Mooney” image) presented many seconds later. We found that this is indeed the case, suggesting that conscious vision may be influenced by priors established by unconscious processing of a fleeting image. PMID:27595010

  13. Activation of the prostaglandin system in response to sleep loss in healthy humans: Potential mediator of increased spontaneous pain

    PubMed Central

    Haack, Monika; Lee, Erin; Cohen, Daniel; Mullington, Janet M.

    2009-01-01

    Insufficient duration of sleep is a highly prevalent behavioral pattern in society that has been shown to cause an increase in spontaneous pain and sensitivity to noxious stimuli. Prostaglandins (PG), in particular PGE2, are key mediators of inflammation and pain, and we investigated whether PGE2 is a potential mediator in sleep-loss induced changes in nociceptive processing. Twenty-four participants (7 females, age 35. 17.1yrs) stayed for 7 days in the Clinical Research Center. After two baseline days, participants were randomly assigned to either three days of 88 hours of total sleep deprivation (TSD, N=15) or 8 hours of sleep per night (N=9), followed by a night of recovery sleep. Participants rated the intensity of various pain-related symptoms every two hours across waking periods on computerized visual analog scales. PGE2 was measured in 24h-urine collections during baseline and third sleep deprivation day. Spontaneous pain, including headache, muscle pain, stomach pain, generalized body pain, and physical discomfort significantly increased by 5 to 14 units on a 100-unit scale during TSD, compared to the sleep condition. Urinary PGE2 metabolite significantly increased by about 30% in TSD over sleep condition. TSD-induced increase in spontaneous pain, in particular headache and muscle pain, was significantly correlated with increase in PGE2 metabolite. Activation of the PGE2 system appears to be a potential mediator of increased spontaneous pain in response to insufficient sleep. PMID:19560866

  14. Vaccination of Rhesus Macaques with Recombinant Mycobacterium bovis Bacillus Calmette-Guérin Env V3 Elicits Neutralizing Antibody-Mediated Protection against Simian-Human Immunodeficiency Virus with a Homologous but Not a Heterologous V3 Motif

    PubMed Central

    Someya, Kenji; Cecilia, Dayaraj; Ami, Yasushi; Nakasone, Tadashi; Matsuo, Kazuhiro; Burda, Sherri; Yamamoto, Hiroshi; Yoshino, Naoto; Kaizu, Masahiko; Ando, Shuji; Okuda, Kenji; Zolla-Pazner, Susan; Yamazaki, Shudo; Yamamoto, Naoki; Honda, Mitsuo

    2005-01-01

    Although the correlates of vaccine-induced protection against human immunodeficiency virus type 1 (HIV-1) are not fully known, it is presumed that neutralizing antibodies (NAb) play a role in controlling virus infection. In this study, we examined immune responses elicited in rhesus macaques following vaccination with recombinant Mycobacterium bovis bacillus Calmette-Guérin expressing an HIV-1 Env V3 antigen (rBCG Env V3). We also determined the effect of vaccination on protection against challenge with either a simian-human immunodeficiency virus (SHIV-MN) or a highly pathogenic SHIV strain (SHIV-89.6PD). Immunization with rBCG Env V3 elicited significant levels of NAb for the 24 weeks tested that were predominantly HIV-1 type specific. Sera from the immunized macaques neutralized primary HIV-1 isolates in vitro, including HIV-1BZ167/X4, HIV-1SF2/X4, HIV-1CI2/X4, and, to a lesser extent, HIV-1MNp/X4, all of which contain a V3 sequence homologous to that of rBCG Env V3. In contrast, neutralization was not observed against HIV-1SF33/X4, which has a heterologous V3 sequence, nor was it found against primary HIV-1 R5 isolates from either clade A or B. Furthermore, the viral load in the vaccinated macaques was significantly reduced following low-dose challenge with SHIV-MN, and early plasma viremia was markedly decreased after high-dose SHIV-MN challenge. In contrast, replication of pathogenic SHIV-89.6PD was not affected by vaccination in any of the macaques. Thus, we have shown that immunization with an rBCG Env V3 vaccine elicits a strong, type-specific V3 NAb response in rhesus macaques. While this response was not sufficient to provide protection against a pathogenic SHIV challenge, it was able to significantly reduce the viral load in macaques following challenge with a nonpathogenic SHIV. These observations suggest that rBCG vectors have the potential to deliver an appropriate virus immunogen for desirable immune elicitations. PMID:15650171

  15. Abnormal immune complex processing and spontaneous glomerulonephritis in complement factor H-deficient mice with human complement receptor 1 on erythrocytes.

    PubMed

    Alexander, Jessy J; Hack, Bradley K; Jacob, Alexander; Chang, Anthony; Haas, Mark; Finberg, Robert W; Quigg, Richard J

    2010-09-15

    Complement receptor 1 (CR1) on human erythrocytes (Es) and complement factor H (CFH) on rodent platelets perform immune adherence, which is a function that allows the processing of immune complexes (ICs) bearing C3 by the mononuclear phagocyte system. Similar immune adherence occurs in the glomerular podocyte by CR1 in humans and CFH in rodents. As a model for human IC processing, we studied transgenic mice lacking CFH systemically but with human CR1 on Es. These CR1(hu)Tg/CFH(-/-) mice spontaneously developed proliferative glomerulonephritis, which was accelerated in a chronic serum sickness model by active immunization with heterologous apoferritin. ICs containing Ag, IgG and C3 bound to Es in CR1(hu)Tg/CFH(-/-) mice. In this setting, there was increased IC deposition in glomeruli, attributable to the presence of CR1 on Es, together with the absence of CFH on platelets and podocytes. In the absence of plasma CFH, the accumulated ICs activated complement, which led to spontaneous and chronic serum sickness-induced proliferative glomerulonephritis. These findings illustrate the complexities of complement-dependent IC processing by blood cells and in the glomerulus, and the importance of CFH as a plasma complement regulator.

  16. Assessing pragmatic skills in elicited production.

    PubMed

    de Villiers, Peter

    2004-02-01

    In developing a test of pragmatic skills for children ages 4 to 9 years, we focused on a number of functional language skills that are important for children's success in early schooling and for the development of fluent reading and writing. They included (1) wh-question asking, (2) communicative role taking, (3) linking events in a cohesive narrative, and (4) articulating the mental states of the characters in a story. All of the proposed items provide specific referential support and pragmatic motivation for the forms and content to be produced by the child. The pictured materials and elicitation prompts constrain the range of appropriate utterances, so the children's productions are more easily scored than an open-ended spontaneous speech sample. All tasks described show a clear developmental trend, a clear separation between the performance of typically developing and language-impaired children, and no performance differences between African American English- and Mainstream American English-speaking children.

  17. Electrical Responses and Spontaneous Activity of Human iPS-Derived Neuronal Networks Characterized for 3-month Culture with 4096-Electrode Arrays

    PubMed Central

    Amin, Hayder; Maccione, Alessandro; Marinaro, Federica; Zordan, Stefano; Nieus, Thierry; Berdondini, Luca

    2016-01-01

    The recent availability of human induced pluripotent stem cells (hiPSCs) holds great promise as a novel source of human-derived neurons for cell and tissue therapies as well as for in vitro drug screenings that might replace the use of animal models. However, there is still a considerable lack of knowledge on the functional properties of hiPSC-derived neuronal networks, thus limiting their application. Here, upon optimization of cell culture protocols, we demonstrate that both spontaneous and evoked electrical spiking activities of these networks can be characterized on-chip by taking advantage of the resolution provided by CMOS multielectrode arrays (CMOS-MEAs). These devices feature a large and closely-spaced array of 4096 simultaneously recording electrodes and multi-site on-chip electrical stimulation. Our results show that networks of human-derived neurons can respond to electrical stimulation with a physiological repertoire of spike waveforms after 3 months of cell culture, a period of time during which the network undergoes the expression of developing patterns of spontaneous spiking activity. To achieve this, we have investigated the impact on the network formation and on the emerging network-wide functional properties induced by different biochemical substrates, i.e., poly-dl-ornithine (PDLO), poly-l-ornithine (PLO), and polyethylenimine (PEI), that were used as adhesion promoters for the cell culture. Interestingly, we found that neuronal networks grown on PDLO coated substrates show significantly higher spontaneous firing activity, reliable responses to low-frequency electrical stimuli, and an appropriate level of PSD-95 that may denote a physiological neuronal maturation profile and synapse stabilization. However, our results also suggest that even 3-month culture might not be sufficient for human-derived neuronal network maturation. Taken together, our results highlight the tight relationship existing between substrate coatings and emerging network

  18. Electrical Responses and Spontaneous Activity of Human iPS-Derived Neuronal Networks Characterized for 3-month Culture with 4096-Electrode Arrays.

    PubMed

    Amin, Hayder; Maccione, Alessandro; Marinaro, Federica; Zordan, Stefano; Nieus, Thierry; Berdondini, Luca

    2016-01-01

    The recent availability of human induced pluripotent stem cells (hiPSCs) holds great promise as a novel source of human-derived neurons for cell and tissue therapies as well as for in vitro drug screenings that might replace the use of animal models. However, there is still a considerable lack of knowledge on the functional properties of hiPSC-derived neuronal networks, thus limiting their application. Here, upon optimization of cell culture protocols, we demonstrate that both spontaneous and evoked electrical spiking activities of these networks can be characterized on-chip by taking advantage of the resolution provided by CMOS multielectrode arrays (CMOS-MEAs). These devices feature a large and closely-spaced array of 4096 simultaneously recording electrodes and multi-site on-chip electrical stimulation. Our results show that networks of human-derived neurons can respond to electrical stimulation with a physiological repertoire of spike waveforms after 3 months of cell culture, a period of time during which the network undergoes the expression of developing patterns of spontaneous spiking activity. To achieve this, we have investigated the impact on the network formation and on the emerging network-wide functional properties induced by different biochemical substrates, i.e., poly-dl-ornithine (PDLO), poly-l-ornithine (PLO), and polyethylenimine (PEI), that were used as adhesion promoters for the cell culture. Interestingly, we found that neuronal networks grown on PDLO coated substrates show significantly higher spontaneous firing activity, reliable responses to low-frequency electrical stimuli, and an appropriate level of PSD-95 that may denote a physiological neuronal maturation profile and synapse stabilization. However, our results also suggest that even 3-month culture might not be sufficient for human-derived neuronal network maturation. Taken together, our results highlight the tight relationship existing between substrate coatings and emerging

  19. Electrical Responses and Spontaneous Activity of Human iPS-Derived Neuronal Networks Characterized for 3-month Culture with 4096-Electrode Arrays.

    PubMed

    Amin, Hayder; Maccione, Alessandro; Marinaro, Federica; Zordan, Stefano; Nieus, Thierry; Berdondini, Luca

    2016-01-01

    The recent availability of human induced pluripotent stem cells (hiPSCs) holds great promise as a novel source of human-derived neurons for cell and tissue therapies as well as for in vitro drug screenings that might replace the use of animal models. However, there is still a considerable lack of knowledge on the functional properties of hiPSC-derived neuronal networks, thus limiting their application. Here, upon optimization of cell culture protocols, we demonstrate that both spontaneous and evoked electrical spiking activities of these networks can be characterized on-chip by taking advantage of the resolution provided by CMOS multielectrode arrays (CMOS-MEAs). These devices feature a large and closely-spaced array of 4096 simultaneously recording electrodes and multi-site on-chip electrical stimulation. Our results show that networks of human-derived neurons can respond to electrical stimulation with a physiological repertoire of spike waveforms after 3 months of cell culture, a period of time during which the network undergoes the expression of developing patterns of spontaneous spiking activity. To achieve this, we have investigated the impact on the network formation and on the emerging network-wide functional properties induced by different biochemical substrates, i.e., poly-dl-ornithine (PDLO), poly-l-ornithine (PLO), and polyethylenimine (PEI), that were used as adhesion promoters for the cell culture. Interestingly, we found that neuronal networks grown on PDLO coated substrates show significantly higher spontaneous firing activity, reliable responses to low-frequency electrical stimuli, and an appropriate level of PSD-95 that may denote a physiological neuronal maturation profile and synapse stabilization. However, our results also suggest that even 3-month culture might not be sufficient for human-derived neuronal network maturation. Taken together, our results highlight the tight relationship existing between substrate coatings and emerging network

  20. Post-translational intracellular trafficking determines the type of immune response elicited by DNA vaccines expressing Gag antigen of Human Immunodeficiency Virus Type 1 (HIV-1)

    PubMed Central

    Wallace, Aaron; West, Kim; Rothman, Alan L; Ennis, Francis A; Lu, Shan; Wang, Shixia

    2013-01-01

    In the current study, immune responses induced by Gag DNA vaccines with different designs were evaluated in Balb/C mice. The results demonstrated that the DNA vaccine with the full length wild type gag gene (Wt-Gag) mainly produced Gag antigens intracellularly and induced a higher level of cell-mediated immune (CMI) responses, as measured by IFN-gamma ELISPOT, intracellular cytokine staining (ICS), and cytotoxic T lymphocytes (CTL) assays against a dominant CD8+ T cell epitope (AMQMLKETI). In contrast, the addition of a tissue plasminogen activator (tPA) leader sequence significantly improved overall Gag protein expression/secretion and Gag-specific antibody responses; however, Gag-specific CMI responses were decreased. The mutation of zinc-finger motif changed Gag protein expression patterns and reduced the ability to generate both CMI and antibody responses against Gag. These findings indicate that the structure and post-translational processing of antigens expressed by DNA vaccines play a critical role in eliciting optimal antibody or CMI responses. PMID:23941868

  1. Utilizing Model Eliciting Activities (MEA's) to engage middle school teachers and students in storm water management practices to mitigate human impacts of land development

    NASA Astrophysics Data System (ADS)

    Tazaz, A.; Wilson, R. M.; Schoen, R.; Blumsack, S.; King, L.; Dyehouse, M.

    2013-12-01

    'The Integrating STEM Project' engaged 6-8 grade teachers through activities incorporating mathematics, science and technology incorporating both Next Generation Science Standards (NGSS) and Common Core State Standards-Mathematics (CCSS-Math). A group of researchers from Oceanography, Mathematics, and Education set out to provide middle school teachers with a 2 year intensive STEM integration professional development with a focus on environmental topics and to monitor the achievement outcomes in their students. Over the course of 2 years the researchers created challenging professional development sessions to expand teacher knowledge and teachers were tasked to transform the information gained during the professional development sessions for classroom use. One lesson resource kit presented to the teachers, which was directly applicable to the classroom, included Model Eliciting Activities (MEA's) to explore the positive and negative effects land development has on climate and the environment, and how land development impacts storm water management. MEA's were developed to encourage students to create models to solve complex problems and to allow teachers to investigate students thinking. MEA's are a great curriculum technique used in engineering fields to help engage students by providing hands on activities using real world data and problems. We wish to present the Storm Water Management Resource toolkit including the MEA and present the outcomes observed from student engagement in this activity.

  2. Spontaneous inactivation of human tryptase involves conformational changes consistent with conversion of the active site to a zymogen-like structure.

    PubMed

    Selwood, T; McCaslin, D R; Schechter, N M

    1998-09-22

    The conformational changes accompanying spontaneous inactivation and dextran sulfate (DS) mediated reactivation of the serine protease human tryptase were investigated by analysis of (i) intrinsic fluorescence, (ii) inhibitor binding, and (iii) catalytic efficiency. Spontaneous inactivation produced a marked decrease in fluorescence emission intensity that was reversed by the addition of DS. Fluorescence decreases at high (4.0 microM) and low (0.1 microM) tryptase concentrations were similar at early times and coincided with loss of enzymatic activity but deviated significantly from activity loss at later times by showing a difference in the extent of change. The fluorescence losses were best described by a two-step kinetic model in which the major decrease correlated to activity loss (t1/2 of 4.3 min in 0.2 M NaCl, pH 6.8, 30 degrees C) and was followed by a further decrease (t1/2 approximately 60 min) whose extent differed with tryptase concentration. The ability to bind the competitive inhibitor p-aminobenzamidine was reversibly lost upon spontaneous inactivation, providing evidence for conformational changes affecting the major substrate binding site (S1-pocket). Estimation of catalytic efficiency using an active site titrant showed that the specific activity of tryptase remained unchanged upon inactivation and reactivation. Return of enzymatic activity, intrinsic fluorescence, and the S1 pocket appeared to occur in the same time frame (t1/2 approximately 3 min). These studies indicate that spontaneous inactivation involves reversible changes which convert the active site to a nonfunctional state. The association of activity loss with an intrinsic fluorescence decrease and loss of the S1-pocket is consistent with the disruption of a critical ionic bond at the active site. Formation of this ionic bond is the basis of zymogen activation for the chymotrypsin family of serine proteases. PMID:9748324

  3. Gender differences in preschoolers' help-eliciting communication.

    PubMed

    Thompson, R B

    1999-09-01

    Gender differences in help-eliciting communication and the relationship of such utterances with ability were explored. A sample of 71 preschoolers (38 boys, 33 girls; mean age 4 years 3 months) were videotaped as they solved a difficult puzzle. Spontaneous talk was analyzed for orientation (to whom or to what an utterance referred) and for the frequency of utterances coded as help eliciting. Significant main effects for gender were observed, with more frequent help-eliciting utterances (HEUs) made by the girls than by the boys, particularly HEUs about themselves (self-disclosing). Although the girls' HEUs were not predictive of ability on the puzzle, the boys' were. No gender differences in puzzle-solving ability were observed. Findings are discussed with regard to problem solving and social/linguistic development. PMID:10515069

  4. The L1 protein of human papilloma virus 16 expressed by a fowlpox virus recombinant can assemble into virus-like particles in mammalian cell lines but elicits a non-neutralising humoral response.

    PubMed

    Bissa, Massimiliano; Zanotto, Carlo; Pacchioni, Sole; Volonté, Luca; Venuti, Aldo; Lembo, David; De Giuli Morghen, Carlo; Radaelli, Antonia

    2015-04-01

    Human papilloma virus (HPV)-16 is the prevalent genotype associated with cervical tumours. Virus-like-particle (VLP)-based vaccines have proven to be effective in limiting new infections of high-risk HPVs, but their high cost has hampered their use, especially in the poor developing countries. Avipox-based recombinants are replication-restricted to avian species and represent efficient and safe vectors also for immunocompromised hosts, as they can elicit a complete immune response. A new fowlpox virus recombinant encoding HPV-L1 (FPL1) was engineered and evaluated side-by-side with a FP recombinant co-expressing L1 and green fluorescent protein (FPL1GFP) for correct expression of L1 in vitro in different cell lines, as confirmed by Western blotting, immunofluorescence, real-time PCR, and electron microscopy. Mice were also immunised to determine its immunogenicity. Here, we demonstrate that the FPL1 recombinant better expresses L1 in the absence of GFP, correctly assembles structured capsomers into VLPs, and elicits an immune response in a preclinical animal model. To our knowledge, this is the first report of HPV VLPs assembled in eukaryotic cells using an avipox recombinant.

  5. High-resolution molecular validation of self-renewal and spontaneous differentiation in adipose-tissue derived human mesenchymal stem cells cultured in human platelet lysate

    PubMed Central

    Dudakovic, Amel Dudakovic; Camilleri, Emily; Riester, Scott M.; Lewallen, Eric A.; Kvasha, Sergiy; Chen, Xiaoyue; Radel, Darcie J.; Anderson, Jarett M.; Nair, Asha A.; Evans, Jared M.; Krych, Aaron J.; Smith, Jay; Deyle, David R.; Stein, Janet L.; Stein, Gary S.; Im, Hee-Jeong; Cool, Simon M.; Westendorf, Jennifer J.; Kakar, Sanjeev; Dietz, Allan B.; van Wijnen, Andre J.

    2014-01-01

    Improving the effectiveness of adipose-tissue derived human mesenchymal stromal/stem cells (AMSCs) for skeletal therapies requires a detailed characterization of mechanisms supporting cell proliferation and multi-potency. We investigated the molecular phenotype of AMSCs that were either actively proliferating in platelet lysate or in a basal non-proliferative state. Flow cytometry combined with high-throughput RNA sequencing (RNASeq) and RT-qPCR analyses validate that AMSCs express classic mesenchymal cell surface markers (e.g., CD44, CD73/NT5E, CD90/THY1 and CD105/ENG). Expression of CD90 is selectively elevated at confluence. Self-renewing AMSCs express a standard cell cycle program that successively mediates DNA replication, chromatin packaging, cyto-architectural enlargement and mitotic division. Confluent AMSCs preferentially express genes involved in extracellular matrix (ECM) formation and cellular communication. For example, cell cycle-related biomarkers (e.g., cyclins E2 and B2, transcription factor E2F1) and histone-related genes (e.g., H4, HINFP, NPAT) are elevated in proliferating AMSCs, while ECM genes are strongly upregulated (>10 fold) in quiescent AMSCs. AMSCs also express pluripotency genes (e.g., POU5F1, NANOG, KLF4) and early mesenchymal markers (e.g., NES, ACTA2) consistent with their multipotent phenotype. Strikingly, AMSCs modulate expression of WNT signaling components and switch production of WNT ligands (from WNT5A/WNT5B/WNT7B to WNT2/WNT2B), while up-regulating WNT-related genes (WISP2, SFRP2 and SFRP4). Furthermore, post-proliferative AMSCs spontaneously express fibroblastic, osteogenic, chondrogenic and adipogenic biomarkers when maintained in confluent cultures. Our findings validate the biological properties of self-renewing and multi-potent AMSCs by providing high-resolution quality control data that support their clinical versatility. PMID:24905804

  6. Spontaneous fission

    SciTech Connect

    Hoffman, D.C.

    1993-09-01

    The spontaneous fission (SF) of the heaviest actinides and the transactinides is of particular interest because of the dramatic changes in properties observed in the region of the heavy fermion isotopes and for still heavier elements. The existing experimental information on SF properties including half-life systematics, fragment kinetic-energy and mass-yield distributions, prompt neutron emission, and gamma emission will be reviewed. Possibility for extending studies of SF properties to other regions are considered and the potential for obtaining additional information about low-energy fission properties is discussed.

  7. Expression and localization of collectins in feto-maternal tissues of human first trimester spontaneous abortion and abortion prone mouse model.

    PubMed

    Yadav, A K; Chaudhari, H; Shah, P K; Madan, T

    2016-02-01

    Dysregulation of immune response at the feto-maternal interface during first trimester of pregnancy is one of the leading causes of spontaneous abortion. Previously, we reported differential expression of collectins, soluble pattern recognition molecules involved in immunoregulation, in placental and decidual tissues during spontaneous labor. In the present pilot study, the expression of collectins was analyzed in the inflamed human gestational tissues of spontaneous abortion ('SA') and in 13.5 dpc placental tissues from resorption survived embryos of murine model (CBA/J X DBA/2J). Transcripts of SP-A were significantly down-regulated and SP-D were significantly up-regulated in placental and decidual tissues of 'SA' group compared to that of 'normal' group. Immunostaining for SP-D and MBL proteins was positive in placental and decidual tissues. However, levels of SP-D and MBL proteins were not significantly altered in placental as well as in decidual tissues of 'SA' group in comparison to the 'normal' group. Placental tissues of viable embryos from the abortion prone mouse model showed significantly enhanced expression of mSP-A and mSP-D transcripts at 13.5 day post coitus (dpc) and 14.5 dpc compared to the control group (CBA/J X Balb/c). Mouse collectins were localized in placental tissues (13.5 dpc), with increased staining in murine model compared to control. Human and murine data together indicate that SP-A, SP-D and MBL are synthesised in early gestational tissues, and may contribute to regulation of immune response at the feto-maternal interface during pregnancy.

  8. Durable immunity to oncogenic human papillomaviruses elicited by adjuvanted recombinant Adeno-associated virus-like particle immunogen displaying L2 17-36 epitopes.

    PubMed

    Jagu, Subhashini; Karanam, Balusubramanyam; Wang, Joshua W; Zayed, Hatem; Weghofer, Margit; Brendle, Sarah A; Balogh, Karla K; Tossi, Kerstin Pino; Roden, Richard B S; Christensen, Neil D

    2015-10-13

    Vaccination with the minor capsid protein L2, notably the 17-36 neutralizing epitope, induces broadly protective antibodies, although the neutralizing titers attained in serum are substantially lower than for the licensed L1 VLP vaccines. Here we examine the impact of other less reactogenic adjuvants upon the induction of durable neutralizing serum antibody responses and protective immunity after vaccination with HPV16 and HPV31 L2 amino acids 17-36 inserted at positions 587 and 453 of VP3, respectively, for surface display on Adeno-Associated Virus 2-like particles [AAVLP (HPV16/31L2)]. Mice were vaccinated three times subcutaneously with AAVLP (HPV16/31L2) at two week intervals at several doses either alone or formulated with alum, alum and MPL, RIBI adjuvant or Cervarix. The use of adjuvant with AAVLP (HPV16/31L2) was necessary in mice for the induction of L2-specific neutralizing antibody and protection against vaginal challenge with HPV16. While use of alum was sufficient to elicit durable protection (>3 months after the final immunization), antibody titers were increased by addition of MPL and RIBI adjuvants. To determine the breadth of immunity, rabbits were immunized three times with AAVLP (HPV16/31L2) either alone, formulated with alum±MPL, or RIBI adjuvants, and after serum collection, the animals were concurrently challenged with HPV16/31/35/39/45/58/59 quasivirions or cottontail rabbit papillomavirus (CRPV) at 6 or 12 months post-immunization. Strong protection against all HPV types was observed at both 6 and 12 months post-immunization, including robust protection in rabbits receiving the vaccine without adjuvant. In summary, vaccination with AAVLP presenting HPV L2 17-36 epitopes at two sites on their surface induced cross-neutralizing serum antibody, immunity against HPV16 in the genital tract, and long-term protection against skin challenge with the 7 most common oncogenic HPV types when using a clinically relevant adjuvant.

  9. Durable immunity to oncogenic human papillomaviruses elicited by adjuvanted recombinant Adeno-associated virus-like particle immunogen displaying L2 17-36 epitopes.

    PubMed

    Jagu, Subhashini; Karanam, Balusubramanyam; Wang, Joshua W; Zayed, Hatem; Weghofer, Margit; Brendle, Sarah A; Balogh, Karla K; Tossi, Kerstin Pino; Roden, Richard B S; Christensen, Neil D

    2015-10-13

    Vaccination with the minor capsid protein L2, notably the 17-36 neutralizing epitope, induces broadly protective antibodies, although the neutralizing titers attained in serum are substantially lower than for the licensed L1 VLP vaccines. Here we examine the impact of other less reactogenic adjuvants upon the induction of durable neutralizing serum antibody responses and protective immunity after vaccination with HPV16 and HPV31 L2 amino acids 17-36 inserted at positions 587 and 453 of VP3, respectively, for surface display on Adeno-Associated Virus 2-like particles [AAVLP (HPV16/31L2)]. Mice were vaccinated three times subcutaneously with AAVLP (HPV16/31L2) at two week intervals at several doses either alone or formulated with alum, alum and MPL, RIBI adjuvant or Cervarix. The use of adjuvant with AAVLP (HPV16/31L2) was necessary in mice for the induction of L2-specific neutralizing antibody and protection against vaginal challenge with HPV16. While use of alum was sufficient to elicit durable protection (>3 months after the final immunization), antibody titers were increased by addition of MPL and RIBI adjuvants. To determine the breadth of immunity, rabbits were immunized three times with AAVLP (HPV16/31L2) either alone, formulated with alum±MPL, or RIBI adjuvants, and after serum collection, the animals were concurrently challenged with HPV16/31/35/39/45/58/59 quasivirions or cottontail rabbit papillomavirus (CRPV) at 6 or 12 months post-immunization. Strong protection against all HPV types was observed at both 6 and 12 months post-immunization, including robust protection in rabbits receiving the vaccine without adjuvant. In summary, vaccination with AAVLP presenting HPV L2 17-36 epitopes at two sites on their surface induced cross-neutralizing serum antibody, immunity against HPV16 in the genital tract, and long-term protection against skin challenge with the 7 most common oncogenic HPV types when using a clinically relevant adjuvant. PMID:26382603

  10. Durable immunity to oncogenic human papillomaviruses elicited by adjuvanted recombinant Adeno-associated virus-like particle immunogen displaying L2 17–36 epitopes

    PubMed Central

    Jagu, Subhashini; Karanam, Balusubramanyam; Wang, Joshua W.; Zayed, Hatem; Weghofer, Margit; Brendle, Sarah A.; Balogh, Karla K.; Tossi, Kerstin Pino; Roden, Richard B.S.; Christensen, Neil D.

    2016-01-01

    Vaccination with the minor capsid protein L2, notably the 17–36 neutralizing epitope, induces broadly protective antibodies, although the neutralizing titers attained in serum are substantially lower than for the licensed L1 VLP vaccines. Here we examine the impact of other less reactogenic adjuvants upon the induction of durable neutralizing serum antibody responses and protective immunity after vaccination with HPV16 and HPV31 L2 amino acids 17–36 inserted at positions 587 and 453 of VP3, respectively, for surface display on Adeno-Associated Virus 2-like particles [AAVLP (HPV16/31L2)]. Mice were vaccinated three times subcutaneously with AAVLP (HPV16/31L2) at two week intervals at several doses either alone or formulated with alum, alum and MPL, RIBI adjuvant or Cervarix. The use of adjuvant with AAVLP (HPV16/31L2) was necessary in mice for the induction of L2-specific neutralizing antibody and protection against vaginal challenge with HPV16. While use of alum was sufficient to elicit durable protection (>3 months after the final immunization), antibody titers were increased by addition of MPL and RIBI adjuvants. To determine the breadth of immunity, rabbits were immunized three times with AAVLP (HPV16/31L2) either alone, formulated with alum ± MPL, or RIBI adjuvants, and after serum collection, the animals were concurrently challenged with HPV16/31/35/39/45/58/59 quasivirions or cottontail rabbit papillomavirus (CRPV) at 6 or 12 months post-immunization. Strong protection against all HPV types was observed at both 6 and 12 months post-immunization, including robust protection in rabbits receiving the vaccine without adjuvant. In summary, vaccination with AAVLP presenting HPV L2 17–36 epitopes at two sites on their surface induced cross-neutralizing serum antibody, immunity against HPV16 in the genital tract, and long-term protection against skin challenge with the 7 most common oncogenic HPV types when using a clinically relevant adjuvant. PMID:26382603

  11. Analysis of linear energy transfers and quality factors of charged particles produced by spontaneous fission neutrons from 252Cf and 244Pu in the human body.

    PubMed

    Endo, Akira; Sato, Tatsuhiko

    2013-04-01

    Absorbed doses, linear energy transfers (LETs) and quality factors of secondary charged particles in organs and tissues, generated via the interactions of the spontaneous fission neutrons from (252)Cf and (244)Pu within the human body, were studied using the Particle and Heavy Ion Transport Code System (PHITS) coupled with the ICRP Reference Phantom. Both the absorbed doses and the quality factors in target organs generally decrease with increasing distance from the source organ. The analysis of LET distributions of secondary charged particles led to the identification of the relationship between LET spectra and target-source organ locations. A comparison between human body-averaged mean quality factors and fluence-averaged radiation weighting factors showed that the current numerical conventions for the radiation weighting factors of neutrons, updated in ICRP103, and the quality factors for internal exposure are valid.

  12. Transcriptome interrogation of human myometrium identifies differentially expressed sense-antisense pairs of protein-coding and long non-coding RNA genes in spontaneous labor at term

    PubMed Central

    Romero, Roberto; Tarca, Adi; Chaemsaithong, Piya; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Jia, Hui; Hassan, Sonia S.; Kalita, Cynthia A.; Cai, Juan; Yeo, Lami; Lipovich, Leonard

    2014-01-01

    Objective The mechanisms responsible for normal and abnormal parturition are poorly understood. Myometrial activation leading to regular uterine contractions is a key component of labor. Dysfunctional labor (arrest of dilatation and/or descent) is a leading indication for cesarean delivery. Compelling evidence suggests that most of these disorders are functional in nature, and not the result of cephalopelvic disproportion. The methodology and the datasets afforded by the post-genomic era provide novel opportunities to understand and target gene functions in these disorders. In 2012, the ENCODE Consortium elucidated the extraordinary abundance and functional complexity of long non-coding RNA genes in the human genome. The purpose of the study was to identify differentially expressed long non-coding RNA genes in human myometrium in women in spontaneous labor at term. Materials and Methods Myometrium was obtained from women undergoing cesarean deliveries who were not in labor (n=19) and women in spontaneous labor at term (n=20). RNA was extracted and profiled using an Illumina® microarray platform. The analysis of the protein coding genes from this study has been previously reported. Here, we have used computational approaches to bound the extent of long non-coding RNA representation on this platform, and to identify co-differentially expressed and correlated pairs of long non-coding RNA genes and protein-coding genes sharing the same genomic loci. Results Upon considering more than 18,498 distinct lncRNA genes compiled nonredundantly from public experimental data sources, and interrogating 2,634 that matched Illumina microarray probes, we identified co-differential expression and correlation at two genomic loci that contain coding-lncRNA gene pairs: SOCS2-AK054607 and LMCD1-NR_024065 in women in spontaneous labor at term. This co-differential expression and correlation was validated by qRT-PCR, an independent experimental method. Intriguingly, one of the two lnc

  13. Individual differences in physiological flexibility predict spontaneous avoidance.

    PubMed

    Aldao, Amelia; Dixon-Gordon, Katherine L; De Los Reyes, Andres

    2016-08-01

    People often regulate their emotions by resorting to avoidance, a putatively maladaptive strategy. Prior work suggests that increased psychopathology symptoms predict greater spontaneous utilisation of this strategy. Extending this work, we examined whether heightened resting cardiac vagal tone (which reflects a general ability to regulate emotions in line with contextual demands) predicts decreased spontaneous avoidance. In Study 1, greater resting vagal tone was associated with reduced spontaneous avoidance in response to disgust-eliciting pictures, beyond anxiety and depression symptoms and emotional reactivity. In Study 2, resting vagal tone interacted with anxiety and depression symptoms to predict spontaneous avoidance in response to disgust-eliciting film clips. The positive association between symptoms and spontaneous avoidance was more pronounced among participants with reduced resting vagal tone. Thus, increased resting vagal tone might protect against the use of avoidance. Our findings highlight the importance of assessing both subjective and biological processes when studying individual differences in emotion regulation.

  14. Humanized HLA-DR4 Mice Fed with the Protozoan Pathogen of Oysters Perkinsus Marinus (Dermo) Do Not Develop Noticeable Pathology but Elicit Systemic Immunity

    PubMed Central

    Kleschenko, Yuliya; Pow-Sang, Luis; Brumeanu, Teodor D.; Villasante, Eileen Franke; Vasta, Gerardo R.; Fernández-Robledo, José-Antonio; Casares, Sofia

    2014-01-01

    Perkinsus marinus (Phylum Perkinsozoa) is a marine protozoan parasite responsible for “Dermo” disease in oysters, which has caused extensive damage to the shellfish industry and estuarine environment. The infection prevalence has been estimated in some areas to be as high as 100%, often causing death of infected oysters within 1–2 years post-infection. Human consumption of the parasites via infected oysters is thus likely to occur, but to our knowledge the effect of oral consumption of P. marinus has not been investigated in humans or other mammals. To address the question we used humanized mice expressing HLA-DR4 molecules and lacking expression of mouse MHC-class II molecules (DR4.EA0) in such a way that CD4 T cell responses are solely restricted by the human HLA-DR4 molecule. The DR4.EA0 mice did not develop diarrhea or any detectable pathology in the gastrointestinal tract or lungs following single or repeated feedings with live P. marinus parasites. Furthermore, lymphocyte populations in the gut associated lymphoid tissue and spleen were unaltered in the parasite-fed mice ruling out local or systemic inflammation. Notably, naïve DR4.EA0 mice had antibodies (IgM and IgG) reacting against P. marinus parasites whereas parasite specific T cell responses were undetectable. Feeding with P. marinus boosted the antibody responses and stimulated specific cellular (IFNγ) immunity to the oyster parasite. Our data indicate the ability of P. marinus parasites to induce systemic immunity in DR4.EA0 mice without causing noticeable pathology, and support rationale grounds for using genetically engineered P. marinus as a new oral vaccine platform to induce systemic immunity against infectious agents. PMID:24498105

  15. Synergetic Effects of K, Ca, Cu and Zn in Human Semen in Relation to Parameters Indicative of Spontaneous Hyperactivation of Spermatozoa

    PubMed Central

    Bolanca, Ivan; Obhodas, Jasmina; Ljiljak, Dejan; Matjacic, Lidija; Kuna, Krunoslav

    2016-01-01

    We have observed that sperm quality parameters indicative of spermatozoa hyperactivation such are lower “linearity” and “straightness”, and as showed by this research “elongation”, were more pronounced in patients with normal spermiogram compared to the group of men with reduced sperm motility who were undergoing routine in vitro fertilisation. The research encompassed 97 men diagnosed with normozoospermia (n = 20), asthenozoospermia (n = 54) and oligoasthenozoospermia (n = 23). The findings indicate that sperm quality of patients with normal spermiogram diagnosed according to WHO criteria, may be compromised by showing premature spontaneous hyperactivation which can decrease the chances of natural conception. We assessed synergistic effects of multiple chemical elements in ejaculated semen to find if premature spontaneous hyperactivation of spermatozoa can be a sign of imbalanced semen composition especially of elements K, Ca, Cu and Zn. Human semen samples showing low or high baseline status of chemical elements concentrations were found in samples from all three diagnostic groups. However, correlation of K/Ca and Cu/Zn ratios, taking into account samples from all three groups of men, were negative at statistical significance level p = 0.01. We tested if the negative correlation between K/Ca and Cu/Zn ratio works for greater number of semen samples. We found the negative correlation to be valid for 175 semen samples at statistical significance of p = 0.00002. The ratio of K/Ca and Cu/Zn, i.e. increased concentrations of K and Zn in comparison to concentrations of Ca and Cu, were associated with a decrease of “straightness” in the group of men with normal spermiogram and pronounced spontaneous hyperactivation of spermatozoa, implying that these elements act in synergy and that the balance of elements and not their absolute concentrations plays the major role in premature spermatozoa hyperactivation in ejaculated semen. PMID:27031102

  16. Sterilizing immunity elicited by Neisseria meningitidis carriage shows broader protection than predicted by serum antibody cross-reactivity in CEACAM1-humanized mice.

    PubMed

    Johswich, Kay O; McCaw, Shannon E; Strobel, Lea; Frosch, Matthias; Gray-Owen, Scott D

    2015-01-01

    Neisseria meningitidis asymptomatically colonizes the human upper respiratory tract but is also the cause of meningitis and severe septicemia. Carriage or disease evokes an immune response against the infecting strain. Hitherto, we have known little about the breadth of immunity induced by natural carriage of a single strain or its implications for subsequent infectious challenge. In this study, we establish that transgenic mice expressing human CEACAM1 support nasal colonization by a variety of strains of different capsular types. Next, we nasally challenged these mice with either of the N. meningitidis strains H44/76 (serogroup B, ST-32) and 90/18311 (serogroup C, ST-11), while following the induction of strain-specific immunoglobulin. When these antisera were tested for reactivity with a diverse panel of N. meningitidis strains, very low levels of antibody were detected against all meningococcal strains, yet a mutually exclusive "fingerprint" of high-level cross-reactivity toward certain strains became apparent. To test the efficacy of these responses for protection against subsequent challenge, CEACAM1-humanized mice exposed to strain 90/18311 were then rechallenged with different N. meningitidis strains. As expected, the mice were immune to challenge with the same strain and with a closely related ST-11 strain, 38VI, while H44/76 (ST-32) could still colonize these animals. Notably, however, despite the paucity of detectable humoral response against strain 196/87 (ST-32), this strain was unable to colonize the 90/18311-exposed mice. Combined, our data suggest that current approaches may underestimate the actual breadth of mucosal protection gained through natural exposure to N. meningitidis strains. PMID:25368118

  17. Healthy human CSF promotes glial differentiation of hESC-derived neural cells while retaining spontaneous activity in existing neuronal networks.

    PubMed

    Kiiski, Heikki; Aänismaa, Riikka; Tenhunen, Jyrki; Hagman, Sanna; Ylä-Outinen, Laura; Aho, Antti; Yli-Hankala, Arvi; Bendel, Stepani; Skottman, Heli; Narkilahti, Susanna

    2013-06-15

    The possibilities of human pluripotent stem cell-derived neural cells from the basic research tool to a treatment option in regenerative medicine have been well recognized. These cells also offer an interesting tool for in vitro models of neuronal networks to be used for drug screening and neurotoxicological studies and for patient/disease specific in vitro models. Here, as aiming to develop a reductionistic in vitro human neuronal network model, we tested whether human embryonic stem cell (hESC)-derived neural cells could be cultured in human cerebrospinal fluid (CSF) in order to better mimic the in vivo conditions. Our results showed that CSF altered the differentiation of hESC-derived neural cells towards glial cells at the expense of neuronal differentiation. The proliferation rate was reduced in CSF cultures. However, even though the use of CSF as the culture medium altered the glial vs. neuronal differentiation rate, the pre-existing spontaneous activity of the neuronal networks persisted throughout the study. These results suggest that it is possible to develop fully human cell and culture-based environments that can further be modified for various in vitro modeling purposes.

  18. Env-2dCD4 S60C complexes act as super immunogens and elicit potent, broadly neutralizing antibodies against clinically relevant human immunodeficiency virus type 1 (HIV-1).

    PubMed

    Killick, Mark A; Grant, Michelle L; Cerutti, Nichole M; Capovilla, Alexio; Papathanasopoulos, Maria A

    2015-11-17

    The ability to induce a broadly neutralizing antibody (bNAb) response following vaccination is regarded as a crucial aspect in developing an effective vaccine against human immunodeficiency virus type 1 (HIV-1). The bNAbs target the HIV-1 envelope glycoprotein (Env) which is exposed on the virus surface, thereby preventing cell entry. To date, conventional vaccine approaches such as the use of Env-based immunogens have been unsuccessful. We expressed, purified, characterized and evaluated the immunogenicity of several unique HIV-1 subtype C Env immunogens in small animals. Here we report that vaccine immunogens based on Env liganded to a two domain CD4 variant, 2dCD4(S60C) are capable of consistently eliciting potent, broadly neutralizing antibody responses in New Zealand white rabbits against a panel of clinically relevant HIV-1 pseudoviruses. This was irrespective of the Env protein subtype and context. Importantly, depletion of the anti-CD4 antibodies appeared to abrogate the neutralization activity in the rabbit sera. Taken together, this data suggests that the Env-2dCD4(S60C) complexes described here are "super" immunogens, and potentially immunofocus antibody responses to a unique epitope spanning the 2dCD4(60C). Recent data from the two available anti-CD4 monoclonal antibodies, Ibalizumab and CD4-Ig (and bispecific variants thereof) have highlighted that the use of these broad and potent entry inhibitors could circumvent the need for a conventional vaccine targeting HIV-1. Overall, the ability of the unique Env-2dCD4(S60C) complexes to elicit potent bNAb responses has not been described previously, reinforcing that further investigation for their utility in preventing and controlling HIV-1/SIV infection is warranted. PMID:26432912

  19. WITHDRAWN: Erythrodiol-3-acetate isolated from Styrax japonica elicits the inhibition of UV-induced gelatinases B in cultured human keratinocyte cells.

    PubMed

    Moon, Hyungin; Jung, Jae-Chul

    2007-02-26

    Methanol and aqueous extracts of Styrax japonica Sieb. et Zucc used traditionally for the treatments of skin elastic materials were screened in vitro for the gelatinases B inhibitor actions. Erythrodiol-3-acetate (E) from the stem barks of S. japonica showed significant gelatinase B inhibition in human keratinocyte cells caused by ultraviolet irradiation. Here we investigated the effect of E, which was isolated from S. japonica on UV-induced premature skin aging. We studied the effect of E on UV-induced gelatinase B expression in an immortalized human keratinocyte cell line, in vitro. Acute UV irradiation induced gelatinase B expression at the protein levels and E suppressed this UV-induced gelatinase B expression in a dose-dependent manner. Taken together, these results show that E can prevent the harmful effects of UV that lead to skin aging or skin cancer. Therefore, we suggest that E should be viewed as a potential therapeutic agent for preventing and/or treating premature skin aging. PMID:17329089

  20. Spontaneous Number Representation in Mosquitofish

    ERIC Educational Resources Information Center

    Dadda, Marco; Piffer, Laura; Agrillo, Christian; Bisazza, Angelo

    2009-01-01

    While there is convincing evidence that preverbal human infants and non-human primates can spontaneously represent number, considerable debate surrounds the possibility that such capacity is also present in other animals. Fish show a remarkable ability to discriminate between different numbers of social companions. Previous work has demonstrated…

  1. Viability of human ovarian tissue confirmed 5 years after freezing with spontaneous ice-formation by autografting and chorio-allantoic membrane culture.

    PubMed

    Isachenko, Vladimir; Orth, Ingrid; Isachenko, Evgenia; Mallmann, Peter; Peters, Doris; Schmidt, Torsten; Morgenstern, Bernd; Foth, Dolores; Hanstein, Bettina; Rahimi, Gohar

    2013-06-01

    To achieve optimal and uniform outcomes, slow cooling protocols for human ovarian tissues generally initiate ice formation at high sub-zero temperatures (-6 to -9 °C). The aim of the study was to investigate the function of ovarian tissue that had unintentionally self seeded at -20 °C during the freezing step, by examining its development following chicken embryonic chorioallantoic membrane (CAM) grafting and after transplantation back to the patient. Ovarian tissue was frozen in 6% (v/v) dimethyl sulfoxide, 6% (v/v) ethylene glycol and 0.15M sucrose which had self-seeded at -20 °C. Five years after cryopreservation, 8 pieces were thawed and transplanted back to the patient. Two small (1 × 2 × 1 mm) pieces of this thawed tissue were cultured in a CAM-system for 5 days to assess the tissue viability. The autografted ovarian tissue re-established spontaneous menstrual bleeding within five months and raised serum 17-β Estradiol from 19 to 330 pg/ml. Ultrasound revealed a dominant follicle at the site of the transplanted tissue in the follicular phase after the menstrual bleed. Analysis of the CAM cultured tissue established that 88% of the primordial follicles are degenerated and there was limited in growth of blood vessels. In conclusion, in spite of the damage caused by the cryopreservation with spontaneous ice-formation the viability could be confirmed by CAM culture and the restoration of ovarian function after auto-transplantation.

  2. Spontaneous Decoding of the Timing and Content of Human Object Perception from Cortical Surface Recordings Reveals Complementary Information in the Event-Related Potential and Broadband Spectral Change.

    PubMed

    Miller, Kai J; Schalk, Gerwin; Hermes, Dora; Ojemann, Jeffrey G; Rao, Rajesh P N

    2016-01-01

    The link between object perception and neural activity in visual cortical areas is a problem of fundamental importance in neuroscience. Here we show that electrical potentials from the ventral temporal cortical surface in humans contain sufficient information for spontaneous and near-instantaneous identification of a subject's perceptual state. Electrocorticographic (ECoG) arrays were placed on the subtemporal cortical surface of seven epilepsy patients. Grayscale images of faces and houses were displayed rapidly in random sequence. We developed a template projection approach to decode the continuous ECoG data stream spontaneously, predicting the occurrence, timing and type of visual stimulus. In this setting, we evaluated the independent and joint use of two well-studied features of brain signals, broadband changes in the frequency power spectrum of the potential and deflections in the raw potential trace (event-related potential; ERP). Our ability to predict both the timing of stimulus onset and the type of image was best when we used a combination of both the broadband response and ERP, suggesting that they capture different and complementary aspects of the subject's perceptual state. Specifically, we were able to predict the timing and type of 96% of all stimuli, with less than 5% false positive rate and a ~20ms error in timing. PMID:26820899

  3. Spontaneous Decoding of the Timing and Content of Human Object Perception from Cortical Surface Recordings Reveals Complementary Information in the Event-Related Potential and Broadband Spectral Change

    PubMed Central

    Miller, Kai J.; Schalk, Gerwin; Hermes, Dora; Ojemann, Jeffrey G.; Rao, Rajesh P. N.

    2016-01-01

    The link between object perception and neural activity in visual cortical areas is a problem of fundamental importance in neuroscience. Here we show that electrical potentials from the ventral temporal cortical surface in humans contain sufficient information for spontaneous and near-instantaneous identification of a subject’s perceptual state. Electrocorticographic (ECoG) arrays were placed on the subtemporal cortical surface of seven epilepsy patients. Grayscale images of faces and houses were displayed rapidly in random sequence. We developed a template projection approach to decode the continuous ECoG data stream spontaneously, predicting the occurrence, timing and type of visual stimulus. In this setting, we evaluated the independent and joint use of two well-studied features of brain signals, broadband changes in the frequency power spectrum of the potential and deflections in the raw potential trace (event-related potential; ERP). Our ability to predict both the timing of stimulus onset and the type of image was best when we used a combination of both the broadband response and ERP, suggesting that they capture different and complementary aspects of the subject’s perceptual state. Specifically, we were able to predict the timing and type of 96% of all stimuli, with less than 5% false positive rate and a ~20ms error in timing. PMID:26820899

  4. Spontaneous triadic engagement in bonobos (Pan paniscus) and chimpanzees (Pan troglodytes).

    PubMed

    MacLean, Evan; Hare, Brian

    2013-08-01

    Humans are believed to have evolved a unique motivation to participate in joint activities that first develops during infancy and supports the development of shared intentionality. We conducted five experiments with bonobos (Pan paniscus) and chimpanzees (Pan troglodytes) (Total n = 119) to assess their motivation to spontaneously participate in joint activities with a conspecific or a human. We found that even the youngest subjects preferred to interact together with a human and a toy rather than engaging in an identical game alone. In addition, we found that subjects could spontaneously interact with a human in a turn-taking game involving passing a ball back and forth and used behaviors to elicit additional interaction when the game was disrupted. However, when paired with a conspecific, subjects preferred to interact with an object individually rather than together. Our results indicate that nonhuman apes are motivated to engage in triadic activities if they occur spontaneously with humans and require a minimum amount of coordination. These findings leave open the question of whether these activities are coordinated through shared intentions.

  5. Cigarette smoke and α,β-unsaturated aldehydes elicit VEGF release through the p38 MAPK pathway in human airway smooth muscle cells and lung fibroblasts

    PubMed Central

    Volpi, Giorgia; Facchinetti, Fabrizio; Moretto, Nadia; Civelli, Maurizio; Patacchini, Riccardo

    2011-01-01

    BACKGROUND AND PURPOSE Vascular endothelial growth factor (VEGF) is an angiogenic factor known to be elevated in the sputum of asymptomatic smokers as well as smokers with bronchitis type of chronic obstructive pulmonary disease. The aim of this study was to investigate whether acute exposure to cigarette smoke extract altered VEGF production in lung parenchymal cells. EXPERIMENTAL APPROACH We exposed human airway smooth muscle cells (ASMC), normal human lung fibroblasts (NHLF) and small airways epithelial cells (SAEC) to aqueous cigarette smoke extract (CSE) in order to investigate the effect of cigarette smoke on VEGF expression and release. KEY RESULTS Vascular endothelial growth factor release was elevated by sub-toxic concentrations of CSE in both ASMC and NHLF, but not in SAEC. CSE-evoked VEGF release was mimicked by its component acrolein at concentrations (10–100 µM) found in CSE, and prevented by the antioxidant and α,β-unsaturated aldehyde scavenger, N-acetylcysteine (NAC). Both CSE and acrolein (30 µM) induced VEGF mRNA expression in ASMC cultures, suggesting an effect at transcriptional level. Crotonaldehyde and 4-hydroxy-2-nonenal, an endogenous α,β-unsaturated aldehyde, stimulated VEGF release, as did H2O2. CSE-evoked VEGF release was accompanied by rapid and lasting phosphorylation of p38 MAPK (mitogen-activated protein kinase), which was abolished by NAC and mimicked by acrolein. Both CSE- and acrolein-evoked VEGF release were blocked by selective inhibition of p38 MAPK signalling. CONCLUSIONS AND IMPLICATIONS α,β-Unsaturated aldehydes and possibly reactive oxygen species contained in cigarette smoke stimulate VEGF expression and release from pulmonary cells through p38 MAPK signalling. PMID:21306579

  6. Alpha-Fe(2)O(3) elicits diameter-dependent effects during exposure to an in vitro model of the human placenta.

    PubMed

    Faust, James J; Zhang, Wen; Chen, Yongsheng; Capco, David G

    2014-02-01

    Iron oxide nanoparticles offer unique possibilities due to the change in their physico-chemical parameters when synthesized on the nanoscale (10(-9) m) compared to their bulk forms. While novel uses exist for these materials when synthesized as nanoparticles, their unintended effects on the human body and specifically during pregnancy remain ill defined. In this study, an iron oxide nanoparticle, α-Fe2O3, was employed and the potential toxicity due to exposure was assessed in the widely used model human placental cell line BeWo b30. These cells were grown as epithelia, and subsequently assessed for their epithelial integrity, reactive oxygen species production and cellular viability, ultrastructural and morphological disruption, and genotoxicity as a result of exposure to α-Fe2O3 nanoparticles. Transepithelial electrical resistance indicated that exposure to the large (50 and 78 nm), but not small (15 nm) diameter particles of α-Fe2O3 nanomaterial resulted in leakiness of the epithelium. Exposure to the large diameters of 50 and 78 nm resulted in increases in cell death and reactive oxygen species. Disruption of junctional integrity as monitored by immunolocalization of the tight junction protein ZO-1 was found to occur as a consequence of exposure to large diameter NPs. It was found that there was reduction in the number of microvilli responsible for increased surface area for nutrient absorption after exposing the epithelia to large diameter NPs. Finally, genotoxicity as assessed by DNA microarray and confirmed by QPCR indicated that the large diameter particles (78 nm) induce apoptosis in these cells. These data indicate that large (50 and 78 nm), but not small (15 nm) α-Fe2O3 nanoparticles disrupt the barrier function of this epithelium as assessed by in vitro analysis. PMID:24463955

  7. Alpha-Fe(2)O(3) elicits diameter-dependent effects during exposure to an in vitro model of the human placenta.

    PubMed

    Faust, James J; Zhang, Wen; Chen, Yongsheng; Capco, David G

    2014-02-01

    Iron oxide nanoparticles offer unique possibilities due to the change in their physico-chemical parameters when synthesized on the nanoscale (10(-9) m) compared to their bulk forms. While novel uses exist for these materials when synthesized as nanoparticles, their unintended effects on the human body and specifically during pregnancy remain ill defined. In this study, an iron oxide nanoparticle, α-Fe2O3, was employed and the potential toxicity due to exposure was assessed in the widely used model human placental cell line BeWo b30. These cells were grown as epithelia, and subsequently assessed for their epithelial integrity, reactive oxygen species production and cellular viability, ultrastructural and morphological disruption, and genotoxicity as a result of exposure to α-Fe2O3 nanoparticles. Transepithelial electrical resistance indicated that exposure to the large (50 and 78 nm), but not small (15 nm) diameter particles of α-Fe2O3 nanomaterial resulted in leakiness of the epithelium. Exposure to the large diameters of 50 and 78 nm resulted in increases in cell death and reactive oxygen species. Disruption of junctional integrity as monitored by immunolocalization of the tight junction protein ZO-1 was found to occur as a consequence of exposure to large diameter NPs. It was found that there was reduction in the number of microvilli responsible for increased surface area for nutrient absorption after exposing the epithelia to large diameter NPs. Finally, genotoxicity as assessed by DNA microarray and confirmed by QPCR indicated that the large diameter particles (78 nm) induce apoptosis in these cells. These data indicate that large (50 and 78 nm), but not small (15 nm) α-Fe2O3 nanoparticles disrupt the barrier function of this epithelium as assessed by in vitro analysis.

  8. In vivo responses of cutaneous C-mechanosensitive neurons in mouse to punctate chemical stimuli that elicit itch and nociceptive sensations in humans.

    PubMed

    Ma, C; Nie, H; Gu, Q; Sikand, P; Lamotte, R H

    2012-01-01

    Native cowhage spicules, and heat-inactivated spicules containing histamine or capsaicin, evoke similar sensations of itch and nociceptive sensations in humans. In ongoing studies of the peripheral neural mechanisms of chemical itch and pain in the mouse, extracellular electrophysiological recordings were obtained, in vivo, from the cell bodies of mechanosensitive nociceptive neurons in response to spicule stimuli delivered to their cutaneous receptive fields (RFs) on the distal hindlimb. A total of 43 mechanosensitive, cutaneous, nociceptive neurons with axonal conduction velocities in the C-fiber range (C-nociceptors) were classified as CM if responsive to noxious mechanical stimuli, such as pinch, or CMH if responsive to noxious mechanical and heat stimuli (51°C, 5 s). The tips of native cowhage spicules, or heat-inactivated spicules containing histamine or capsaicin, were applied to the RF. Heat-inactivated spicules containing no chemical produced only a transient response occurring during insertion. Of the 43 mechanosensitive nociceptors recorded, 20 of the 25 CMHs responded to capsaicin, and of these, 13 also responded to cowhage and/or histamine. In contrast, none of the 18 CMs responded to any of the chemical stimuli. The time course of the mean discharge rate of CMHs was similar in response to each type of spicule and generally similar, although reaching a peak earlier, to the temporal profiles of itch and nociceptive sensations evoked by the same stimuli in humans. These findings are consistent with the hypothesis that the itch and nociceptive sensations evoked by these punctuate chemical stimuli are mediated at least in part by the activity of mechanoheat-sensitive C-nociceptors. In contrast, activity in mechanosensitive C-nociceptors that do not respond to heat or to pruritic chemicals is hypothesized as contributing to pain but not to itch. PMID:21994268

  9. Graphene Nanoribbons Elicit Cell Specific Uptake and Delivery Via Activation of Epidermal Growth Factor Receptor Enhanced by Human PapillomaVirus E5 Protein

    PubMed Central

    Chowdhury, Sayan Mullick; Mannepalli, Prady; Sitharaman, Balaji

    2014-01-01

    Ligands such as peptides, antibodies or other epitopes bind and activate specific cell receptors, and are employed for targeted cellular delivery of pharmaceuticals such as drugs, genes and imaging agents. Herein, we show that oxidized graphene nanoribbons, non-covalently functionalized with PEG-DSPE (1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N[amino(polyethyleneglycol)]) (O-GNR-PEG-DSPE) activate epidermal growth factor receptors (EGFRs). This activation generates predominantly dynamin-dependent macropinocytosis-like response, and results in significant O-GNR-PEG-DSPE uptake into cells with high EGFR expression. Cells with an integrated human papillomavirus (HPV) genome also show increased uptake due to the modulation of the activated EFGR by the viral protein E5. We demonstrate that this cell specific uptake of O-GNR-PEG-DSPE can be exploited to achieve significantly enhanced drug efficacies even in drug resistant cells. These results have implications towards the development of active targeting and delivery agents without ligand functionalization for use in the diagnosis and treatment of pathologies that overexpress EGFR or mediated by HPV. PMID:24980059

  10. Replication-attenuated Human Adenoviral Type 4 vectors elicit capsid dependent enhanced innate immune responses that are partially dependent upon interactions with the complement system

    PubMed Central

    Hartman, Zachary C.; Appledorn, Daniel M.; Serra, Delila; Glass, Oliver; Mendelson, Todd; Clay, Timothy M.; Amalfitano, Andrea

    2009-01-01

    Human Adenovirus Type 4 (HAdV-4) is responsible for epidemic outbreaks of Acute Respiratory Disease (especially in military recruits), and is known to cause significant morbidity with several reported cases of mortality. However, we do not understand why this serotype causes such high morbidity, and have little insight into the immunobiology of HAdV-4 infections. We have now developed a replication attenuated HAdV-4 vector system, and through it, demonstrate that HAdV-4 virions have enhanced infectivity of certain cell types and reveal aspects of the serotype-specific heightened innate immunogenicity of infectious HAdV-4 capsids both in vitro and in vivo. We further found that elements of this serotype-specific immunogenicity were dependent upon interactions with the complement system. These findings provide insights into the mechanisms possibly underlying the known morbidity accompanying wild-type HAdV-4 infections as well as highlight important considerations when considering development of alternative serotype vectors. PMID:18280530

  11. Multisensory interactions elicited by audiovisual stimuli presented peripherally in a visual attention task: a behavioral and event-related potential study in humans.

    PubMed

    Wu, Jinglong; Li, Qi; Bai, Ou; Touge, Tetsuo

    2009-12-01

    We applied behavioral and event-related potential measurements to study human multisensory interactions induced by audiovisual (AV) stimuli presented peripherally in a visual attention task in which an irrelevant auditory stimulus occasionally accompanied the visual stimulus. A stream of visual, auditory, and AV stimuli was randomly presented to the left or right side of the subjects; subjects covertly attended to the visual stimuli on either the left or right side and promptly responded to visual targets on that side. Behavioral results showed that responses to AV stimuli were faster and more accurate than those to visual stimuli only. Three event-related potential components related to AV interactions were identified: (1) over the right temporal area, approximately 200 to 220 milliseconds; (2) over the centromedial area, approximately 290 to 310 milliseconds; and (3) over the left and right ventral temporal area, approximately 290 to 310 milliseconds. We found that these interaction effects occurred slightly later than those reported in previously published AV interaction studies in which AV stimuli were presented centrally. Our results suggest that the retinotopic location of stimuli affects AV interactions occurring at later stages of cognitive processing in response to a visual attention task.

  12. Infection of human urethral epithelium with Neisseria gonorrhoeae elicits an upregulation of host anti-apoptotic factors and protects cells from staurosporine-induced apoptosis.

    PubMed

    Binnicker, Matthew J; Williams, Richard D; Apicella, Michael A

    2003-08-01

    In order to better understand the host response to an infection with Neisseria gonorrhoeae, microarray technology was used to analyse the gene expression profile between uninfected and infected human urethral epithelium. The anti-apoptotic genes bfl-1, cox-2 and c-IAP-2 were identified to be upregulated approximately eight-, four- or twofold, respectively, following infection. Subsequent assays including RT-PCR, real time RT-PCR and RNase protection confirmed the increased expression of these apoptotic regulators, and identified that a fourth anti-apoptotic factor, mcl-1, is also upregulated. RT-PCR and RNase protection also showed that key pro-apoptotic factors including bax, bad and bak do not change in expression. Furthermore, our studies demonstrated that infection with the gonococcus partially protects urethral epithelium from apoptosis induced by the protein kinase inhibitor, staurosporine (STS). This work shows that following infection with Neisseria gonorrhoeae, several host anti-apoptotic factors are upregulated. In addition, a gonococcal infection protects host cells from subsequent STS-induced death. The regulation of host cell death by the gonococcus may represent a mechanism employed by this pathogen to survive and proliferate in host epithelium. PMID:12864814

  13. A SILAC-Based Approach Elicits the Proteomic Responses to Vancomycin-Associated Nephrotoxicity in Human Proximal Tubule Epithelial HK-2 Cells.

    PubMed

    Li, Zhi-Ling; Zhou, Shu-Feng

    2016-01-29

    Vancomycin, a widely used antibiotic, often induces nephrotoxicity, however, the molecular targets and underlying mechanisms of this side effect remain unclear. The present study aimed to examine molecular interactome and analyze the signaling pathways related to the vancomycin-induced nephrotoxicity in human proximal tubule epithelial HK-2 cells using the stable isotope labeling by amino acids in cell culture (SILAC) approach. The quantitative proteomic study revealed that there were at least 492 proteins interacting with vancomycin and there were 290 signaling pathways and cellular functions potentially regulated by vancomycin in HK-2 cells. These proteins and pathways played a critical role in the regulation of cell cycle, apoptosis, autophagy, EMT, and ROS generation. These findings suggest that vancomycin-induced proteomic responses in HK-2 cells involvefunctional proteins and pathways that regulate cell cycle, apoptosis, autophagy, and redox homeostasis. This is the first systemic study revealed the networks of signaling pathways and proteomic responses to vancomycin treatment in HK-2 cells, and the data may be used to discriminate the molecular and clinical subtypes and to identify new targets and biomarkers for vancomycin-induced nephrotoxic effect. Further studies are warranted to explore the potential of quantitative proteomic analysis in the identification of new targets and biomarkers for drug-induced renal toxicity.

  14. Global Gene Profiling of Spontaneous Hepatocellular Carcinoma in B6C3F1 Mice: Similarities in the Molecular Landscape with Human Liver Cancer

    PubMed Central

    Hoenerhoff, Mark J.; Pandiri, Arun R.; Lahousse, Stephanie A.; Hong, Hu-Hua; Ton, Tai-Vu; Masinde, Tiwanda; Auerbach, Scott S.; Gerrish, Kevin; Bushel, Pierre R.; Shockley, Keith R.; Peddada, Shyamal D.; Sills, Robert C.

    2016-01-01

    Hepatocellular carcinoma (HCC) is an important cause of morbidity and mortality worldwide. Although the risk factors of human HCC are well known, the molecular pathogenesis of this disease is complex, and in general, treatment options remain poor. The use of rodent models to study human cancer has been extensively pursued, both through genetically engineered rodents and rodent models used in carcinogenicity and toxicology studies. In particular, the B6C3F1 mouse used in the National Toxicology Program (NTP) two-year bioassay has been used to evaluate the carcinogenic effects of environmental and occupational chemicals, and other compounds. The high incidence of spontaneous HCC in the B6C3F1 mouse has challenged its use as a model for chemically induced HCC in terms of relevance to the human disease. Using global gene expression profiling, we identify the dysregulation of several mediators similarly altered in human HCC, including re-expression of fetal oncogenes, upregulation of protooncogenes, downregulation of tumor suppressor genes, and abnormal expression of cell cycle mediators, growth factors, apoptosis regulators, and angiogenesis and extracellular matrix remodeling factors. Although major differences in etiology and pathogenesis remain between human and mouse HCC, there are important similarities in global gene expression and molecular pathways dysregulated in mouse and human HCC. These data provide further support for the use of this model in hazard identification of compounds with potential human carcinogenicity risk, and may help in better understanding the mechanisms of tumorigenesis resulting from chemical exposure in the NTP two-year carcinogenicity bioassay. PMID:21571946

  15. Spontaneous classification in action by a human-enculturated and language-reared bonobo (Pan paniscus) and common chimpanzees (Pan troglodytes).

    PubMed

    Spinozzi, G; Langer, J

    1999-09-01

    The authors investigated the formal features of spontaneous manipulations used by 1 bonobo (Pan paniscus) and 2 common chimpanzees (Pan troglodytes) to classify objects in action. Chimpanzees' manipulations were evenly split between serial, one-at-a-time acts on 1 object and parallel, two-at-a-time acts on 2 or 3 objects. Chimpanzees systematically combined their manipulations into routines to generate class-consistent categories of objects. Their routines featured much reproduction of the same manipulations, planful acts that anticipated follow-up manipulations, and manipulations that were reciprocal to each other to accomplish an end. In all these respects, chimpanzees' manipulations were similar to those of 2-year-old human infants. In others they differed. Chimpanzees' routines were mainly based on a linear integration of manipulations. Classifying in action was only infrequently produced by hierarchically integrated routines.

  16. Comparative analysis of the fusion efficiency elicited by the envelope glycoprotein V1-V5 regions derived from human immunodeficiency virus type 1 transmitted perinatally.

    PubMed

    Guo, Hongyan; Abrahamyan, Levon G; Liu, Chang; Waltke, Mackenzie; Geng, Yunqi; Chen, Qimin; Wood, Charles; Kong, Xiaohong

    2012-12-01

    Understanding the properties of viruses preferentially establishing infection during perinatal transmission of human immunodeficiency virus type 1 (HIV-1) is critical for the development of effective measures to prevent transmission. A previous study demonstrated that the newly transmitted viruses (in infants) of chronically infected mother-infant pairs (MIPs) were fitter in terms of growth, which was imparted by their envelope (Env) glycoprotein V1-V5 regions, than those in the corresponding chronically infected mothers. In order to investigate whether the higher fitness of transmitted viruses was conferred by their higher entry efficiency directed by the V1-V5 regions during perinatal transmission, the fusogenicity of Env containing V1-V5 regions derived from transmitted and non-tranmsmitted viruses of five chronically infected MIPs and two acutely infected MIPs was analysed using two different cell-cell fusion assays. The results showed that, in one chronically infected MIP, a higher fusion efficiency was induced by the infant Env V1-V5 compared with that of the corresponding mother. Moreover, the V4-V5 regions played an important role in discriminating the transmitted and non-transmitted viruses in this pair. However, neither a consistent pattern nor significant differences in fusogenicity mediated by the V1-V5 regions between maternal and infant variants was observed in the other MIPs. This study suggests that there is no consistent and significant correlation between viral fitness selection and entry efficiency directed by the V1-V5 regions during perinatal transmission. Other factors such as the route and timing of transmission may also be involved.

  17. Immunization with Human Papillomavirus 16 L1+E2 Chimeric Capsomers Elicits Cellular Immune Response and Antitumor Activity in a Mouse Model.

    PubMed

    López-Toledo, Gabriela; Schädlich, Lysann; Alonso-Castro, Ángel Josabad; Monroy-García, Alberto; García-Rocha, Rosario; Guido, Miriam C; Gissmann, Lutz; García-Carrancá, Alejandro

    2016-06-01

    Development of cervical cancer is associated with persistent infections by high-risk human papillomavirus (HPV). Although current HPV L1-based prophylactic vaccines prevent infection, they do not help to eliminate prevalent infections or lesions. Our aims were (i) to generate a vaccine combining prophylactic and therapeutic properties by producing chimeric capsomers after fusion of the L1 protein to different fragments of E2 from HPV 16, and (ii) to evaluate their capacity to generate an antitumoral cellular response, while conserving L1 neutralizing epitopes. Chimeric proteins were produced in Escherichia coli and purified by glutathione S-transferase (GST)-affinity chromatography. Their structure was characterized using size exclusion chromatography, sucrose gradient centrifugation, electron microscopy, and anti-L1 enzyme-linked immunosorbent assay. All chimeric proteins form capsomers and heterogeneous aggregates. One, containing part of the carboxy-terminal domain of E2 and its hinge region (L1Δ+E2H/NC, aa 206-307), conserved the neutralizing epitope H16.V5. We then evaluated the capacity of this chimeric protein to induce a cytotoxic T-cell response against HPV 16 E2. In (51)Cr release cytotoxicity assays, splenocytes from C57BL/6 immunized mice recognized and lysed TC-1/E2 cells, which express and present endogenously processed E2 peptides. Moreover, this E2-specific cytotoxic response inhibited the growth of tumors of TC-1/E2 cells in mice. Finally, we identified an epitope (aa 292-301) of E2 involved in this cytotoxic response. We conclude that the L1Δ+E2H/NC chimeric protein produced in bacteria can be an effective and economically interesting candidate for a combined prophylactic and therapeutic vaccine that could help eliminating HPV16-positive low-grade cervical lesions and persistent viral infections, thus preventing the development of lesions and, at the same time, the establishment of new infections. PMID:27058179

  18. Glucose metabolism and the response to insulin by human adipose tissue in spontaneous and experimental obesity. Effects of dietary composition and adipose cell size.

    PubMed

    Salans, L B; Bray, G A; Cushman, S W; Danforth, E; Glennon, J A; Horton, E S; Sims, E A

    1974-03-01

    [1-(14)C]glucose oxidation to CO(2) and conversion into glyceride by adipose tissue from nonobese and obese subjects has been studied in vitro in the presence of varying medium glucose and insulin concentrations as functions of adipose cell size, the composition of the diet, and antecedent weight gain or loss. Increasing medium glucose concentrations enhance the incorporation of glucose carbons by human adipose tissue into CO(2) and glyceride-glycerol. Insulin further stimulates the conversion of glucose carbons into CO(2), but not into glyceride-glycerol. Incorporation of [1-(14)C]glucose into glyceride-fatty acids by these tissues could not be demonstrated under any of the conditions tested. Both adipose cell size and dietary composition influence the in vitro metabolism of glucose in, and the response to insulin by, human adipose tissue. During periods of ingestion of weight-maintenance isocaloric diets of similar carbohydrate, fat, and protein composition, increasing adipose cell size is associated with (a) unchanging rates of glucose oxidation and increasing rates of glucose carbon incorporation into glyceride-glycerol in the absence of insulin, but (b) decreasing stimulation of glucose oxidation by insulin. On the other hand, when cell size is kept constant, increasing dietary carbohydrate intake is associated with an increased basal rate of glucose metabolism and response to insulin by both small and large adipose cells. Thus, the rate of glucose oxidation and the magnitude of the insulin response of large adipose cells from individuals ingesting a high carbohydrate diet may be similar to or greater than that in smaller cells from individuals ingesting an isocaloric lower carbohydrate diet.The alterations in basal glucose metabolism and insulin response observed in adipose tissue from patients with spontaneous obesity are reproduced by weight gain induced experimentally in nonobese volunteers; these metabolic changes are reversible with weight loss. The

  19. The arrhythmogenic human HRC point mutation S96A leads to spontaneous Ca(2+) release due to an impaired ability to buffer store Ca(2+).

    PubMed

    Zhang, Joe Z; McLay, Janet C; Jones, Peter P

    2014-09-01

    The Ser96Ala (S96A) mutation within the histidine rich Ca(2+) binding protein (HRC) has recently been linked to cardiac arrhythmias in idiopathic dilated cardiomyopathy patients, potentially attributable to an increase in spontaneous Ca(2+) release events. However, the molecular mechanism connecting the S96A mutation of HRC to increased Ca(2+) release events remains unclear. Previous findings by our group indicate that these spontaneous Ca(2+) release events may be linked to store overload induced Ca(2+) release (SOICR) via the cardiac ryanodine receptor (RyR2). Therefore, in the present study we sought to determine whether HRC wild type (HRC WT) and S96A mutant (HRC S96A) expression has a direct effect on SOICR. Using both cytosolic and intra-Ca(2+) store measurements in human embryonic kidney cells expressing RyR2, we found that HRC WT significantly inhibited the propensity for SOICR by buffering store free Ca(2+) and inhibiting store Ca(2+) uptake. In contrast, HRC S96A exhibited a markedly suppressed inhibitory effect on SOICR, which was attributed to an impaired ability to buffer store Ca(2+) and reduce store Ca(2+) uptake. In addition to impairing the ability of HRC to regulate bulk store Ca(2+), a proximity ligation assay demonstrated that the S96A mutation also disrupts the Ca(2+) microdomain around the RyR2, as it alters the Ca(2+) dependent association of RyR2 and HRC. Importantly, in contrast to previous reports, the absence of triadin in our experimental model illustrates that the S96A mutation in HRC can alter the propensity for SOICR without any interaction with triadin. Collectively, our results demonstrate that the human HRC mutation S96A leads to an increase in spontaneous Ca(2+) release and ultimately arrhythmias by disrupting the regulation of intra-store free Ca(2+). This is primarily due to an impaired ability to act as an effective bulk and local microdomain store Ca(2+) buffer.

  20. Efficacy of broad-spectrum sunscreens against the suppression of elicitation of delayed-type hypersensitivity responses in humans depends on the level of ultraviolet A protection.

    PubMed

    Moyal, D D; Fourtanier, A M

    2003-04-01

    Sunscreens have been designed to protect against sunburn and their efficacy has, therefore, been labeled by the so-called sun protection factor (SPF). Although this value is well determined using a standardized protocol and it affords a good evaluation of the protection against erythema it may be inadequate to provide a relevant measurement of efficacy against other biologic damages. This is particularly true when action spectra and threshold dose are different from those of erythema. In the case of ultraviolet (UV)-induced immune suppression, the action spectrum is not known, so it cannot be asserted that SPF may accurately predict the level of protection against this endpoint. We addressed this issue by measuring in human volunteers the ability of two broad-spectrum SPF 15 sunscreens with different ultraviolet A (UVA) protection levels, to prevent the alteration of the efferent phase of the local delayed-type hypersensitivity (DTH) response to recall antigens (Multitest Pasteur/Mérieux, Lyon, France) after acute solar-simulated UV exposure. We first determined the ultraviolet radiation (UVR) dose needed to induce a significant DTH inhibition in several groups of 15 volunteers. Two minimal erythemal doses (2 MED) were found to be the minimal immunosuppressive dose (MISD). As a result, the immune DTH response is reduced in average by 36%. The lower doses tested (0.5 and 1 MED) were ineffective. Sunscreen-treated groups were exposed to either 1 or 2 MED x SPF doses. As expected, no alteration in DTH response was observed in the groups exposed to 1 MED x SPF whatever the sunscreen applied. In contrast, after exposure to 2 MED x SPF, the DTH response remained unaltered in the group pretreated with the sunscreen product with the higher protection in the UVA range but was significantly suppressed by 55.7% in the group pretreated with sunscreen with a much lower protection in the UVA range. These data suggest that SPF may not be sufficient to predict the ability of

  1. Spontaneous Electrical Activity of Dionaea muscipula.

    PubMed

    Balotin, N M; Dipalma, J R

    1962-12-21

    Instillation of four to six drops of 3-percent saline in the leaf trap of Dionaea muscipula Ellis causes the appearance of a series of spontaneous action potentials. Mechanical stimulation of the sensitive leaf hair elicits only a single response. Immersion in 3-percent, but not in 1-percent, saline effects a loss of weight in Dionaea but not in the leaves of gardenia or geranium.

  2. Independent development of the Reach and the Grasp in spontaneous self-touching by human infants in the first 6 months

    PubMed Central

    Thomas, Brittany L.; Karl, Jenni M.; Whishaw, Ian Q.

    2015-01-01

    The Dual Visuomotor Channel Theory proposes that visually guided reaching is a composite of two movements, a Reach that advances the hand to contact the target and a Grasp that shapes the digits for target purchase. The theory is supported by biometric analyses of adult reaching, evolutionary contrasts, and differential developmental patterns for the Reach and the Grasp in visually guided reaching in human infants. The present ethological study asked whether there is evidence for a dissociated development for the Reach and the Grasp in nonvisual hand use in very early infancy. The study documents a rich array of spontaneous self-touching behavior in infants during the first 6 months of life and subjected the Reach movements to an analysis in relation to body target, contact type, and Grasp. Video recordings were made of resting alert infants biweekly from birth to 6 months. In younger infants, self-touching targets included the head and trunk. As infants aged, targets became more caudal and included the hips, then legs, and eventually the feet. In younger infants hand contact was mainly made with the dorsum of the hand, but as infants aged, contacts included palmar contacts and eventually grasp and manipulation contacts with the body and clothes. The relative incidence of caudal contacts and palmar contacts increased concurrently and were significantly correlated throughout the period of study. Developmental increases in self-grasping contacts occurred a few weeks after the increase in caudal and palmar contacts. The behavioral and temporal pattern of these spontaneous self-touching movements suggest that the Reach, in which the hand extends to make a palmar self-contact, and the Grasp, in which the digits close and make manipulatory movements, have partially independent developmental profiles. The results additionally suggest that self-touching behavior is an important developmental phase that allows the coordination of the Reach and the Grasp prior to and

  3. Effects of recombinant human insulin-like growth factor I administration on spontaneous and growth hormone (GH)-releasing hormone-stimulated GH secretion in anorexia nervosa.

    PubMed

    Gianotti, L; Pincelli, A I; Scacchi, M; Rolla, M; Bellitti, D; Arvat, E; Lanfranco, F; Torsello, A; Ghigo, E; Cavagnini, F; Müller, E E

    2000-08-01

    Exaggerated GH and reduced insulin-like growth factor I (IGF-I) levels are common features in anorexia nervosa (AN). A reduction of the negative IGF-I feedback could account, in part, for GH hypersecretion. To ascertain this, we studied the effects of recombinant human (rh)IGF-I on spontaneous and GH-releasing hormone (GHRH)-stimulated GH secretion in nine women with AN [body mass index, 14.1 +/- 0.6 kg/m2] and in weight matched controls (normal weight). Mean basal GH concentrations (mGHc) and GHRH (2.0 microg/kg, iv) stimulation were significantly higher in AN. rhIGF-I administration (20 microg/kg, sc) significantly reduced mGHc in AN (P < 0.01), but not normal weight, and inhibited peak GH response to GHRH in both groups; mGHc and peak GH, however, persisted at a significantly higher level in AN. Insulin, glucose, and IGFBP-1 basal levels were similar in both groups. rhIGF-I inhibited insulin in AN, whereas glucose remained unaffected in both groups. IGFBP-1 increased in both groups (P < 0.05), with significantly higher levels in AN. IGFBP-3 was under basal conditions at a lower level in AN (P < 0.05) and remained unaffected by rhIGF-I. This study demonstrates that a low rhIGF-I dose inhibits, but does not normalize, spontaneous and GHRH-stimulated GH secretion in AN, pointing also to the existence of a defective hypothalamic control of GH release. Moreover, the increased IGFBP-1 levels might curtail the negative IGF-I feedback in AN.

  4. Spontaneous γH2AX Foci in Human Solid Tumor-Derived Cell Lines in Relation to p21WAF1 and WIP1 Expression

    PubMed Central

    Mirzayans, Razmik; Andrais, Bonnie; Scott, April; Wang, Ying W.; Weiss, Robert H.; Murray, David

    2015-01-01

    Phosphorylation of H2AX on Ser139 (γH2AX) after exposure to ionizing radiation produces nuclear foci that are detectable by immunofluorescence microscopy. These so-called γH2AX foci have been adopted as quantitative markers for DNA double-strand breaks. High numbers of spontaneous γH2AX foci have also been reported for some human solid tumor-derived cell lines, but the molecular mechanism(s) for this response remains elusive. Here we show that cancer cells (e.g., HCT116; MCF7) that constitutively express detectable levels of p21WAF1 (p21) exhibit low numbers of γH2AX foci (<3/nucleus), whereas p21 knockout cells (HCT116p21−/−) and constitutively low p21-expressing cells (e.g., MDA-MB-231) exhibit high numbers of foci (e.g., >50/nucleus), and that these foci are not associated with apoptosis. The majority (>95%) of cells within HCT116p21−/− and MDA-MB-231 cultures contain high levels of phosphorylated p53, which is localized in the nucleus. We further show an inverse relationship between γH2AX foci and nuclear accumulation of WIP1, an oncogenic phosphatase. Our studies suggest that: (i) p21 deficiency might provide a selective pressure for the emergence of apoptosis-resistant progeny exhibiting genomic instability, manifested as spontaneous γH2AX foci coupled with phosphorylation and nuclear accumulation of p53; and (ii) p21 might contribute to positive regulation of WIP1, resulting in dephosphorylation of γH2AX. PMID:26006237

  5. Goniothalamin prevents the development of chemically induced and spontaneous colitis in rodents and induces apoptosis in the HT-29 human colon tumor cell line.

    PubMed

    Vendramini-Costa, Débora Barbosa; Alcaide, Antonio; Pelizzaro-Rocha, Karin Juliane; Talero, Elena; Ávila-Román, Javier; Garcia-Mauriño, Sofia; Pilli, Ronaldo Aloise; de Carvalho, João Ernesto; Motilva, Virginia

    2016-06-01

    Colon cancer is the third most incident type of cancer worldwide. One of the most important risk factors for colon cancer development are inflammatory bowel diseases (IBD), thus therapies focusing on IBD treatment have great potential to be used in cancer prevention. Nature has been a source of new therapeutic and preventive agents and the racemic form of the styryl-lactone goniothalamin (GTN) has been shown to be a promising antiproliferative agent, with gastroprotective, antinociceptive and anti-inflammatory effects. As inflammation is a well-known tumor promoter, the major goal of this study was to evaluate the therapeutic and preventive potentials of GTN on chemically induced and spontaneous colitis, as well as the cytotoxic effects of GTN on a human colon tumor cell line (HT-29). GTN treatments inhibited TNBS-induced acute and chronic colitis development in Wistar rats, reducing myeloperoxidase levels and inflammatory cells infiltration in the mucosa. In spontaneous-colitis using IL-10 deficient mice (C57BL/6 background), GTN prevented colitis development through downregulation of TNF-α, upregulation of SIRT-1 and inhibition of proliferation (PCNA index), without signs of toxicity after three months of treatment. In HT-29 cells, treatment with 10μM of GTN induced apoptosis by increasing BAX/BCL2, p-JNK1/JNK1, p-P38/P38 ratios as well as through ROS generation. Caspase 8, 9 and 3 activation also occurred, suggesting caspase-dependent apoptotic pathway, culminating in PARP-1 cleavage. Together with previous data, these results show the importance of GTN as a pro-apoptotic, preventive and therapeutic agent for IBD and highlight its potential as a chemopreventive agent for colon cancer.

  6. EFFECTS OF THE ANTIMUTAGENS VANILLIN AND CINNAMALDEHYDE ON SPONTANEOUS MUTATION IN E. COLI LACL STRAINS AND ON GLOBAL GENE EXPRESSION IN SALMONELLA TA104 AND HUMAN HEPG2 CELLS

    EPA Science Inventory

    Effects of the Antimutagens Vanillin and Cinnamaldehyde on Spontaneous Mutation in E. coli lacI Strains and on Global Gene Epression in Salmonella TAlO4 and Human HepG2 Cells

    In previous work we have shown that vanillin (VAN) and cinnamaldehyde (CIN) are dietary antimutag...

  7. Screening and Characterization of Spontaneous Porcine Congenital Heart Defects for Gene Identification and Models of Human Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Rodent models of human congenital birth defects have been instrumental for gene discovery and investigation of mechanisms of disease. However, these models are limited by their small size making practiced intervention or detailed anatomic evaluation difficult. Swine have similar anato...

  8. Omega-3 Fatty Acids from Fish Oil Lower Anxiety, Improve Cognitive Functions and Reduce Spontaneous Locomotor Activity in a Non-Human Primate

    PubMed Central

    Vinot, Nina; Jouin, Mélanie; Lhomme-Duchadeuil, Adrien; Guesnet, Philippe; Alessandri, Jean-Marc; Aujard, Fabienne; Pifferi, Fabien

    2011-01-01

    Omega-3 (ω3) polyunsaturated fatty acids (PUFA) are major components of brain cells membranes. ω3 PUFA-deficient rodents exhibit severe cognitive impairments (learning, memory) that have been linked to alteration of brain glucose utilization or to changes in neurotransmission processes. ω3 PUFA supplementation has been shown to lower anxiety and to improve several cognitive parameters in rodents, while very few data are available in primates. In humans, little is known about the association between anxiety and ω3 fatty acids supplementation and data are divergent about their impact on cognitive functions. Therefore, the development of nutritional studies in non-human primates is needed to disclose whether a long-term supplementation with long-chain ω3 PUFA has an impact on behavioural and cognitive parameters, differently or not from rodents. We address the hypothesis that ω3 PUFA supplementation could lower anxiety and improve cognitive performances of the Grey Mouse Lemur (Microcebus murinus), a nocturnal Malagasy prosimian primate. Adult male mouse lemurs were fed for 5 months on a control diet or on a diet supplemented with long-chain ω3 PUFA (n = 6 per group). Behavioural, cognitive and motor performances were measured using an open field test to evaluate anxiety, a circular platform test to evaluate reference spatial memory, a spontaneous locomotor activity monitoring and a sensory-motor test. ω3-supplemented animals exhibited lower anxiety level compared to control animals, what was accompanied by better performances in a reference spatial memory task (80% of successful trials vs 35% in controls, p<0.05), while the spontaneous locomotor activity was reduced by 31% in ω3-supplemented animals (p<0.001), a parameter that can be linked with lowered anxiety. The long-term dietary ω3 PUFA supplementation positively impacts on anxiety and cognitive performances in the adult mouse lemur. The supplementation of human food with ω3 fatty acids may

  9. Spontaneous bilateral avulsion fracture of the tuberositas tibiae in a New Zealand White rabbit - a counterpart to Osgood-Schlatter disease in humans?

    PubMed

    Nehrbass, D; Arens, D; Zeiter, S

    2015-02-01

    The first reported case describing a spontaneous bilateral avulsion fracture of the tuberositas tibiae in a New Zealand White rabbit is presented. So far in animals, this condition has been only described in dogs and horses. In humans, this condition is also called Osgood-Schlatter disease (OSD) or syndrome, traction apophysitis of the tibial tubercle (ATT) or patellar tendon enthesopathy of the tibial tuberosity respectively. It is mainly seen in young adolescents coinciding with periods of growth spurts. In humans, its pathogenesis is believed to be caused by repetitive tendon/muscle strain at the insertion of the patellar tendon to the immature tibial tuberosity, which has its own secondary ossification center. Morphologically this case is characterized by bilateral chronic avulsion with incomplete separation of the tuberositas tibae, and proximal dislocation of the patella (patella alta). Despite these marked pathological changes, the animal was clinically without findings. Nevertheless, this case emphasizes the need for thorough clinical and radiological examination of rabbits intended for preclinical research studies prior to study begin, especially in orthopedic research. PMID:25435475

  10. Centrosomal Nlp is an oncogenic protein that is gene-amplified in human tumors and causes spontaneous tumorigenesis in transgenic mice.

    PubMed

    Shao, Shujuan; Liu, Rong; Wang, Yang; Song, Yongmei; Zuo, Lihui; Xue, Liyan; Lu, Ning; Hou, Ning; Wang, Mingrong; Yang, Xiao; Zhan, Qimin

    2010-02-01

    Disruption of mitotic events contributes greatly to genomic instability and results in mutator phenotypes. Indeed, abnormalities of mitotic components are closely associated with malignant transformation and tumorigenesis. Here we show that ninein-like protein (Nlp), a recently identified BRCA1-associated centrosomal protein involved in microtubule nucleation and spindle formation, is an oncogenic protein. Nlp was found to be overexpressed in approximately 80% of human breast and lung carcinomas analyzed. In human lung cancers, this deregulated expression was associated with NLP gene amplification. Further analysis revealed that Nlp exhibited strong oncogenic properties; for example, it conferred to NIH3T3 rodent fibroblasts the capacity for anchorage-independent growth in vitro and tumor formation in nude mice. Consistent with these data, transgenic mice overexpressing Nlp displayed spontaneous tumorigenesis in the breast, ovary, and testicle within 60 weeks. In addition, Nlp overexpression induced more rapid onset of radiation-induced lymphoma. Furthermore, mouse embryonic fibroblasts (MEFs) derived from Nlp transgenic mice showed centrosome amplification, suggesting that Nlp overexpression mimics BRCA1 loss. These findings demonstrate that Nlp abnormalities may contribute to genomic instability and tumorigenesis and suggest that Nlp might serve as a potential biomarker for clinical diagnosis and therapeutic target.

  11. Simvastatin Inhibits Toll-like Receptor 8 (TLR8) Signaling in Primary Human Monocytes and Spontaneous Tumor Necrosis Factor Production from Rheumatoid Synovial Membrane Cultures

    PubMed Central

    Mullen, Lisa; Ferdjani, Jason; Sacre, Sandra

    2015-01-01

    Simvastatin has been shown to have antiinflammatory effects that are independent of its serum cholesterol lowering action, but the mechanisms by which these antiinflammatory effects are mediated have not been elucidated. To explore the mechanism involved, the effect of simvastatin on toll-like receptor (TLR) signaling in primary human monocytes was investigated. A short pretreatment with simvastatin dose-dependently inhibited the production of tumor necrosis factor (TNF)-α in response to TLR8 activation (but not TLR2, -4 or -5). Statins are known inhibitors of the cholesterol biosynthetic pathway, but, intriguingly, TLR8 inhibition could not be reversed by addition of mevalonate or geranylgeranyl pyrophosphate, downstream products of cholesterol biosynthesis. TLR8 signaling was examined in HEK 293 cells stably expressing TLR8, where simvastatin inhibited I kappa B kinase (IKK)α/β phosphorylation and subsequent nuclear factor (NF)-κB activation without affecting the pathway to activating protein-1 (AP-1). Because simvastatin has been reported to have antiinflammatory effects in RA patients and TLR8 signaling contributes to TNF production in human RA synovial tissue in culture, simvastatin was tested in these cultures. Simvastatin significantly inhibited the spontaneous release of TNF in this model, which was not reversed by mevalonate. Together, these results demonstrate a hitherto unrecognized mechanism of simvastatin inhibition of TLR8 signaling that may in part explain its beneficial antiinflammatory effects. PMID:26322850

  12. Transplantation of cryopreserved human umbilical cord blood mononuclear cells does not induce sustained recovery after experimental stroke in spontaneously hypertensive rats

    PubMed Central

    Weise, Gesa; Lorenz, Marlene; Pösel, Claudia; Maria Riegelsberger, Ute; Störbeck, Veronika; Kamprad, Manja; Kranz, Alexander; Wagner, Daniel-Christoph; Boltze, Johannes

    2014-01-01

    Previous studies have highlighted the enormous potential of cell-based therapies for stroke not only to prevent ischemic brain damage, but also to amplify endogenous repair processes. Considering its widespread availability and low immunogenicity human umbilical cord blood (HUCB) is a particularly attractive stem cell source. Our goal was to investigate the neurorestorative potential of cryopreserved HUCB mononuclear cells (MNC) after permanent middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats (SHR). Human umbilical cord blood MNC or vehicle solution was administered intravenously 24 hours after MCAO. Experimental groups were as follows: (1) quantitative polymerase chain reaction (PCR) of host-derived growth factors up to 48 hours after stroke; (2) immunohistochemical analysis of astroglial scarring; (3) magnetic resonance imaging (MRI) and weekly behavioral tests for 2 months after stroke. Long-term functional outcome and lesion development on MRI were not beneficially influenced by HUCB MNC therapy. Furthermore, HUCB MNC treatment did not change local growth factor levels and glial scarring extent. In summary, we could not demonstrate neurorestorative properties of HUCB MNC after stroke in SHR. Our results advise caution regarding a prompt translation of cord blood therapy into clinical stroke trials as long as deepened knowledge about its precise modes of action is missing. PMID:24169850

  13. Transplantation of cryopreserved human umbilical cord blood mononuclear cells does not induce sustained recovery after experimental stroke in spontaneously hypertensive rats.

    PubMed

    Weise, Gesa; Lorenz, Marlene; Pösel, Claudia; Maria Riegelsberger, Ute; Störbeck, Veronika; Kamprad, Manja; Kranz, Alexander; Wagner, Daniel-Christoph; Boltze, Johannes

    2014-01-01

    Previous studies have highlighted the enormous potential of cell-based therapies for stroke not only to prevent ischemic brain damage, but also to amplify endogenous repair processes. Considering its widespread availability and low immunogenicity human umbilical cord blood (HUCB) is a particularly attractive stem cell source. Our goal was to investigate the neurorestorative potential of cryopreserved HUCB mononuclear cells (MNC) after permanent middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats (SHR). Human umbilical cord blood MNC or vehicle solution was administered intravenously 24 hours after MCAO. Experimental groups were as follows: (1) quantitative polymerase chain reaction (PCR) of host-derived growth factors up to 48 hours after stroke; (2) immunohistochemical analysis of astroglial scarring; (3) magnetic resonance imaging (MRI) and weekly behavioral tests for 2 months after stroke. Long-term functional outcome and lesion development on MRI were not beneficially influenced by HUCB MNC therapy. Furthermore, HUCB MNC treatment did not change local growth factor levels and glial scarring extent. In summary, we could not demonstrate neurorestorative properties of HUCB MNC after stroke in SHR. Our results advise caution regarding a prompt translation of cord blood therapy into clinical stroke trials as long as deepened knowledge about its precise modes of action is missing. PMID:24169850

  14. Hindlimb unloading elicits anhedonia and sympathovagal imbalance.

    PubMed

    Moffitt, Julia A; Grippo, Angela J; Beltz, Terry G; Johnson, Alan Kim

    2008-10-01

    The hindlimb-unloaded (HU) rat model elicits cardiovascular deconditioning and simulates the physiological adaptations to microgravity or prolonged bed rest in humans. Although psychological deficits have been documented following bed rest and spaceflight in humans, few studies have explored the psychological effects of cardiovascular deconditioning in animal models. Given the bidirectional link established between cardiac autonomic imbalance and psychological depression in both humans and in animal models, we hypothesized that hindlimb unloading would elicit an alteration in sympathovagal tone and behavioral indexes of psychological depression. Male, Sprague-Dawley rats confined to 14 days of HU displayed anhedonia (a core feature of human depression) compared with casted control (CC) animals evidenced by reduced sucrose preference (CC: 81 +/- 2.9% baseline vs. HU: 58 +/- 4.5% baseline) and reduced (rightward shift) operant responding for rewarding electrical brain stimulation (CC: 4.4 +/- 0.3 muA vs. 7.3 +/- 1.0 muA). Cardiac autonomic blockade revealed elevated sympathetic [CC: -54 +/- 14.1 change in (Delta) beats/min vs. HU: -118 +/- 7.6 Delta beats/min] and reduced parasympathetic (CC: 45 +/- 11.8 Delta beats/min vs. HU: 8 +/- 7.3 Delta beats/min) cardiac tone in HU rats. Heart rate variability was reduced (CC: 10 +/- 1.4 ms vs. HU: 7 +/- 0.7 ms), and spectral analysis of blood pressure indicated loss of total, low-, and high-frequency power, consistent with attenuated baroreflex function. These data indicate that cardiovascular deconditioning results in sympathovagal imbalance and behavioral signs consistent with psychological depression. These findings further elucidate the pathophysiological link between cardiovascular diseases and affective disorders.

  15. Elicitation of natural language representations of uncertainty using computer technology

    SciTech Connect

    Tonn, B.; Goeltz, R.; Travis, C.; Tennessee Univ., Knoxville, TN )

    1989-01-01

    Knowledge elicitation is an important aspect of risk analysis. Knowledge about risks must be accurately elicited from experts for use in risk assessments. Knowledge and perceptions of risks must also be accurately elicited from the public in order to intelligently perform policy analysis and develop and implement programs. Oak Ridge National Laboratory is developing computer technology to effectively and efficiently elicit knowledge from experts and the public. This paper discusses software developed to elicit natural language representations of uncertainty. The software is written in Common Lisp and resides on VAX Computers System and Symbolics Lisp machines. The software has three goals, to determine preferences for using natural language terms for representing uncertainty; likelihood rankings of the terms; and how likelihood estimates are combined to form new terms. The first two goals relate to providing useful results for those interested in risk communication. The third relates to providing cognitive data to further our understanding of people's decision making under uncertainty. The software is used to elicit natural language terms used to express the likelihood of various agents causing cancer in humans and cancer resulting in various maladies, and the likelihood of everyday events. 6 refs., 4 figs., 4 tabs.

  16. Direct evidence on the immune-mediated spontaneous regression of human cancer: an incentive for pharmaceutical companies to develop a novel anti-cancer vaccine.

    PubMed

    Saleh, F; Renno, W; Klepacek, I; Ibrahim, G; Dashti, H; Asfar, S; Behbehani, A; Al-Sayer, H; Dashti, A; Kerry, Crotty

    2005-01-01

    To develop an effective pharmaceutical treatment for a disease, we need to fully understand the biological behavior of that disease, especially when dealing with cancer. The current available treatment for cancer may help in lessening the burden of the disease or, on certain occasions, in increasing the survival of the patient. However, a total eradication of cancer remains the researchers' hope. Some of the discoveries in the field of medicine relied on observations of natural events. Among these events is the spontaneous regression of cancer. It has been argued that such regression could be immunologically-mediated, but no direct evidence has been shown to support such an argument. We, hereby, provide compelling evidence that spontaneous cancer regression in humans is immunologically-mediated, hoping that the results from this study would stimulate the pharmaceutical industry to focus more on cancer vaccine immunotherapy. Our results showed that patients with >3 primary melanomas (very rare group among cancer patients) develop significant histopathological spontaneous regression of further melanomas that they could acquire during their life (P=0.0080) as compared to patients with single primary melanoma where the phenomenon of spontaneous regression is absent or minimal. It seems that such regression resulted from the repeated exposure to the tumor which mimics a self-immunization process. Analysis of the regressing tumors revealed heavy infiltration by T lymphocytes as compared to non-regressing tumors (P<0.0001), the predominant of which were T cytotoxic rather than T helper. Mature dendritic cells were also found in significant number (P<0.0001) in the regressing tumors as compared to the non regressing ones, which demonstrate an active involvement of the different arms of the immune system in the multiple primary melanoma patients in the process of tumor regression. Also, MHC expression was significantly higher in the regressing versus the non

  17. Human salivary gland acinar cells spontaneously form three-dimensional structures and change the protein expression patterns.

    PubMed

    Chan, Yen-Hui; Huang, Tsung-Wei; Young, Tai-Horng; Lou, Pei-Jen

    2011-11-01

    Applying tissue engineering principles to design an auto-secretory device is a potential solution for patients suffering loss of salivary gland function. However, the largest challenge in implementing this solution is the primary culture of human salivary gland cells, because the cells are highly differentiated and difficult to expand in vitro. This situation leads to the lack of reports on the in vitro cell biology and physiology of human salivary gland cells. This study used a low-calcium culture system to selectively cultivate human parotid gland acinar (PGAC) cells from tissues with high purity in cell composition. This condition enables PGAC cells to continuously proliferate and retain the phenotypes of epithelial acinar cells to express secreting products (α-amylase) and function-related proteins (aquaporin-3, aquaporin-5, and ZO-1). Notably, when the cells reached confluence, three-dimensional (3D) cell aggregates were observed in crowded regions. These self-formed cell spheres were termed post-confluence structures (PCSs). Unexpectedly, despite being cultured in the same media, cells in PCSs exhibited higher expression levels and different expression patterns of function-related proteins compared to the two-dimensional (2D) cells. Translocation of aquoporin-3 from cytosolic to alongside the cell boundaries, and of ZO-1 molecules to the boundary of the PCSs were also observed. These observations suggest that when PGAC cells cultured on the 2D substrate would form PCSs without the help of 3D scaffolds and retain certain differentiation and polarity. This phenomenon implies that it is possible to introduce 2D substrates instead of 3D scaffolds into artificial salivary gland tissue engineering.

  18. No Effects of Acute Exposure to Wi-Fi Electromagnetic Fields on Spontaneous EEG Activity and Psychomotor Vigilance in Healthy Human Volunteers.

    PubMed

    Zentai, Norbert; Csathó, Árpád; Trunk, Attila; Fiocchi, Serena; Parazzini, Marta; Ravazzani, Paolo; Thuróczy, György; Hernádi, István

    2015-12-01

    Mobile equipment use of wireless fidelity (Wi-Fi) signal modulation has increased exponentially in the past few decades. However, there is inconclusive scientific evidence concerning the potential risks associated with the energy deposition in the brain from Wi-Fi and whether Wi-Fi electromagnetism interacts with cognitive function. In this study we investigated possible neurocognitive effects caused by Wi-Fi exposure. First, we constructed a Wi-Fi exposure system from commercial parts. Dosimetry was first assessed by free space radiofrequency field measurements. The experimental exposure system was then modeled based on real geometry and physical characteristics. Specific absorption rate (SAR) calculations were performed using a whole-body, realistic human voxel model with values corresponding to conventional everyday Wi-Fi exposure (peak SAR10g level was 99.22 mW/kg with 1 W output power and 100% duty cycle). Then, in two provocation experiments involving healthy human volunteers we tested for two hypotheses: 1. Whether a 60 min long 2.4 GHz Wi-Fi exposure affects the spectral power of spontaneous awake electroencephalographic (sEEG) activity (N = 25); and 2. Whether similar Wi-Fi exposure modulates the sustained attention measured by reaction time in a computerized psychomotor vigilance test (PVT) (N = 19). EEG data were recorded at midline electrode sites while volunteers watched a silent documentary. In the PVT task, button press reaction time was recorded. No measurable effects of acute Wi-Fi exposure were found on spectral power of sEEG or reaction time in the psychomotor vigilance test. These results indicate that a single, 60 min Wi-Fi exposure does not alter human oscillatory brain function or objective measures of sustained attention. PMID:26600173

  19. No Effects of Acute Exposure to Wi-Fi Electromagnetic Fields on Spontaneous EEG Activity and Psychomotor Vigilance in Healthy Human Volunteers.

    PubMed

    Zentai, Norbert; Csathó, Árpád; Trunk, Attila; Fiocchi, Serena; Parazzini, Marta; Ravazzani, Paolo; Thuróczy, György; Hernádi, István

    2015-12-01

    Mobile equipment use of wireless fidelity (Wi-Fi) signal modulation has increased exponentially in the past few decades. However, there is inconclusive scientific evidence concerning the potential risks associated with the energy deposition in the brain from Wi-Fi and whether Wi-Fi electromagnetism interacts with cognitive function. In this study we investigated possible neurocognitive effects caused by Wi-Fi exposure. First, we constructed a Wi-Fi exposure system from commercial parts. Dosimetry was first assessed by free space radiofrequency field measurements. The experimental exposure system was then modeled based on real geometry and physical characteristics. Specific absorption rate (SAR) calculations were performed using a whole-body, realistic human voxel model with values corresponding to conventional everyday Wi-Fi exposure (peak SAR10g level was 99.22 mW/kg with 1 W output power and 100% duty cycle). Then, in two provocation experiments involving healthy human volunteers we tested for two hypotheses: 1. Whether a 60 min long 2.4 GHz Wi-Fi exposure affects the spectral power of spontaneous awake electroencephalographic (sEEG) activity (N = 25); and 2. Whether similar Wi-Fi exposure modulates the sustained attention measured by reaction time in a computerized psychomotor vigilance test (PVT) (N = 19). EEG data were recorded at midline electrode sites while volunteers watched a silent documentary. In the PVT task, button press reaction time was recorded. No measurable effects of acute Wi-Fi exposure were found on spectral power of sEEG or reaction time in the psychomotor vigilance test. These results indicate that a single, 60 min Wi-Fi exposure does not alter human oscillatory brain function or objective measures of sustained attention.

  20. Quinacrine induces apoptosis in human leukemia K562 cells via p38 MAPK-elicited BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression

    SciTech Connect

    Changchien, Jung-Jung; Chen, Ying-Jung; Huang, Chia-Hui; Cheng, Tian-Lu; Lin, Shinne-Ren; Chang, Long-Sen

    2015-04-01

    Although previous studies have revealed the anti-cancer activity of quinacrine, its effect on leukemia is not clearly resolved. We sought to explore the cytotoxic effect and mechanism of quinacrine action in human leukemia K562 cells. Quinacrine induced K562 cell apoptosis accompanied with ROS generation, mitochondrial depolarization, and down-regulation of BCL2L1 and BCL2. Upon exposure to quinacrine, ROS-mediated p38 MAPK activation and ERK inactivation were observed in K562 cells. Quinacrine-induced cell death and mitochondrial depolarization were suppressed by the p38MAPK inhibitor SB202190 and constitutively active MEK1 over-expression. Activation of p38 MAPK was shown to promote BCL2 degradation. Further, ERK inactivation suppressed c-Jun-mediated transcriptional expression of BCL2L1. Over-expression of BCL2L1 and BCL2 attenuated quinacrine-evoked mitochondrial depolarization and rescued the viability of quinacrine-treated cells. Taken together, our data indicate that quinacrine-induced K562 cell apoptosis is mediated through mitochondrial alterations triggered by p38 MAPK-mediated BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression. - Highlights: • Quinacrine induces K562 cell apoptosis via down-regulation of BCL2 and BCL2L1. • Quinacrine induces p38 MAPK activation and ERK inactivation in K562 cells. • Quinacrine elicits p38 MAPK-mediated BCL2 down-regulation. • Quinacrine suppresses ERK/c-Jun-mediated BCL2L1 expression.

  1. [Recurrent spontaneous abortions].

    PubMed

    Salat-Baroux, J

    1988-01-01

    The process of fertilization in humans, is remarkably inefficient. Spontaneous abortion is estimated to be between 15 and 20% of all clinical pregnancies, and the early spontaneous abortion rate is closer to 30-50% of fertilized ova. Not all authors agree on the definition of "recurrent spontaneous abortion" (RSA), so the frequency of repeated pregnancy wastage is difficult to determine; from empirically derived data, it has been estimated to range between 0.4 and 0.8%. Because of the various etiologies of RSA, their association in determining an abortive event, it is difficult to evaluate their exact incidence. Moreover, their is no prospective study on this subject, so it is advisable to distinguish between the admitted causes, the likely factors, and the etiologies to be evaluated. In the first group, the congenital or acquired müllerian anomalies (especially the septate uterus), represent about 25% of the RSA, but a lot of problems concerning the physiopathology are still debated, even if the rate of pregnancies after surgery ranges around 50% in certain series. On the other hand, the genetic factors, identified especially with the banding technique, are undeniable: however, although the rate of chromosomal aberrations in the offspring (Monosomy X, Trisony 16, Triploidy) is very high (50 to 60% of spontaneous abortions in the first trimester of pregnancy), when couples with usual abortions are subjected to karyotypic analysis, genetic anomalies (especially translocations) are been noted in only 6.2% of the women and 2.6% of the men. In the second group, the infective factors (chlamydiae, toxoplasma and mycoplasma) are difficult to analyse since the serology is not sufficient without a real proof of an endometrial colonization. Among the endocrinological causes, the classical luteal phase deficiency remains a subject of controversy (estimated between 3 and 30%) not only for the establishment of the diagnosis, but also for the efficiency of progesterone

  2. Differential Transcriptomic Analysis of Spontaneous Lung Tumors in B6C3F1 Mice: Comparison to Human Non–Small Cell Lung Cancer

    PubMed Central

    Pandiri, Arun R.; Sills, Robert C.; Ziglioli, Vincent; Ton, Thai-Vu T.; Hong, Hue–Hua L.; Lahousse, Stephanie A.; Gerrish, Kevin E.; Auerbach, Scott S.; Shockley, Keith R.; Bushel, Pierre R.; Peddada, Shyamal D.; Hoenerhoff, Mark J.

    2016-01-01

    Lung cancer is the leading cause of cancer-related death in people and is mainly due to environmental factors such as smoking and radon. The National Toxicology Program (NTP) tests various chemicals and mixtures for their carcinogenic hazard potential. In the NTP chronic bioassay using B6C3F1 mice, the incidence of lung tumors in treated and control animals is second only to the liver tumors. In order to study the molecular mechanisms of chemically induced lung tumors, an understanding of the genetic changes that occur in spontaneous lung (SL) tumors from untreated control animals is needed. The authors have evaluated the differential transcriptomic changes within SL tumors compared to normal lungs from untreated age-matched animals. Within SL tumors, several canonical pathways associated with cancer (eukaryotic initiation factor 2 signaling, RhoA signaling, PTEN signaling, and mammalian target of rapamycin signaling), metabolism (Inositol phosphate metabolism, mitochondrial dysfunction, and purine and pyramidine metabolism), and immune responses (FcγR-mediated phagocytosis, clathrin-mediated endocytosis, interleukin 8 signaling, and CXCR4 signaling) were altered. Meta-analysis of murine SL tumors and human non–small cell lung cancer transcriptomic data sets revealed a high concordance. These data provide important information on the differential transcriptomic changes in murine SL tumors that will be critical to our understanding of chemically induced lung tumors and will aid in hazard analysis in the NTP 2-year carcinogenicity bioassays. PMID:22688403

  3. Intravenous human umbilical cord blood transplantation for stroke: impact on infarct volume and caspase-3-dependent cell death in spontaneously hypertensive rats.

    PubMed

    Riegelsberger, Ute-Maria; Deten, Alexander; Pösel, Claudia; Zille, Marietta; Kranz, Alexander; Boltze, Johannes; Wagner, Daniel-Christoph

    2011-01-01

    Transplantation of human umbilical cord blood cells (HUCBC) produces reliable behavioral and morphological improvements in animal models of stroke. However, the mechanisms of action still have not been fully elucidated. The aim of the present study is the evaluation of potential neuroprotective effects produced by HUCBC in terms of reduced infarct volume and caspase-3-dependent cell death. Permanent middle cerebral artery occlusion was induced in 90 spontaneously hypertensive rats. The animals were randomly assigned to the control group (n=49) or the verum group (n=41). The cell suspension (8 × 10(6) HUCBC per kilogram bodyweight) or vehicle solution was intravenously administered 24h after stroke onset. Fifty subjects (n=25/25) were sacrificed after 25, 48, 72 and 96h, and brain specimens were removed for immunohistochemistry for MAP2, cleaved caspase-3 (casp3) and GFAP. Another 42 animals (n=26/16) were sacrificed after 0, 6, 24, 36 and 48h and their brains processed for quantitative PCR for casp3 and survivin. The infarct volume remained stable over the entire experimental period. However, cleaved casp3 activity increased significantly in the infarct border zone within the same time frame. Numerous cleaved casp3-positive cells were colocalized with the astrocytic marker GFAP, whereas cleavage of neuronal casp3 was observed rarely. Neither the infarct volume nor casp3 activity was significantly affected by cell transplantation. Delayed systemic transplantation of HUCBC failed to produce neuroprotective effects in a permanent stroke model using premorbid subjects.

  4. Construction of a Rated Speech Corpus of L2 Learners' Spontaneous Speech

    ERIC Educational Resources Information Center

    Yoon, Su-Youn; Pierce, Lisa; Huensch, Amanda; Juul, Eric; Perkins, Samantha; Sproat, Richard; Hasegawa-Johnson, Mark

    2009-01-01

    This work reports on the construction of a rated database of spontaneous speech produced by second language (L2) learners of English. Spontaneous speech was collected from 28 L2 speakers representing six language backgrounds and five different proficiency levels. Speech was elicited using formats similar to that of the TOEFL iBT and the Speaking…

  5. Reward positivity elicited by predictive cues.

    PubMed

    Holroyd, Clay B; Krigolson, Olav E; Lee, Seung

    2011-03-30

    A recent theory holds that a component of the human event-related brain potential called the reward positivity reflects a reward prediction error signal. We investigated this idea in gambling-like task in which, on each trial, a visual stimulus predicted a subsequent rewarding or nonrewarding outcome with 80% probability. Consistent with earlier results, we found that the reward positivity was larger to unexpected than to expected outcomes. In addition, we found that the predictive cues also elicited a reward positivity, as proposed by the theory. These results indicate that the reward positivity reflects the initial assessment of whether a trial will end in success or failure and the reappraisal of that information once the outcome actually occurs.

  6. Spontaneous sensorimotor coupling with multipart music.

    PubMed

    Hurley, Brian K; Martens, Peter A; Janata, Petr

    2014-08-01

    Music often evokes spontaneous movements in listeners that are synchronized with the music, a phenomenon that has been characterized as being in "the groove." However, the musical factors that contribute to listeners' initiation of stimulus-coupled action remain unclear. Evidence suggests that newly appearing objects in auditory scenes orient listeners' attention, and that in multipart music, newly appearing instrument or voice parts can engage listeners' attention and elicit arousal. We posit that attentional engagement with music can influence listeners' spontaneous stimulus-coupled movement. Here, 2 experiments-involving participants with and without musical training-tested the effect of staggering instrument entrances across time and varying the number of concurrent instrument parts within novel multipart music on listeners' engagement with the music, as assessed by spontaneous sensorimotor behavior and self-reports. Experiment 1 assessed listeners' moment-to-moment ratings of perceived groove, and Experiment 2 examined their spontaneous tapping and head movements. We found that, for both musically trained and untrained participants, music with more instruments led to higher ratings of perceived groove, and that music with staggered instrument entrances elicited both increased sensorimotor coupling and increased reports of perceived groove. Although untrained participants were more likely to rate music as higher in groove, trained participants showed greater propensity for tapping along, and they did so more accurately. The quality of synchronization of head movements with the music, however, did not differ as a function of training. Our results shed new light on the relationship between complex musical scenes, attention, and spontaneous sensorimotor behavior.

  7. Clinical holistic medicine: induction of spontaneous remission of cancer by recovery of the human character and the purpose of life (the life mission).

    PubMed

    Ventegodt, Soren; Morad, Mohammed; Hyam, Eytan; Merrick, Joav

    2004-05-26

    The recovery of the human character and purpose of life with consciousness-based medicine seems to be able to induce spontaneous remissions in several diseases. On two different occasions, we observed breast tumors reduced to less than half their original diameters (clinically judged) during a holistic session, when working with the patients in accordance with the holistic process theory of healing, the life mission theory, and the theory of human character. One tumor was histologically diagnosed as malign breast cancer prior to the session, while the other was under examination. As both patients had the affected regions of the breast surgically removed immediately after the session, we are unable to determine if they were actually healed by the holistic treatment. We find it extremely interesting that the size of a tumor can be reduced dramatically within a few hours of holistic treatment, when the patient is highly motivated for personal development. The reduction of tumor size is in accordance with the holistic view that many types of cancer are caused by emotional and existential disturbances. From a holistic perspective, cancer can be understood as a simple disturbance of the cells, arising from the tissue holding on to a trauma with strong emotional content. This is called "a blockage", where the function of the cells is changed from their original function in the tissue to a function of holding emotions. The reduction of the tumor in the two cases happened when old painful emotions were identified in the tissues, in and around the tumor, and processed into understanding; when the patients finally did let go of negative beliefs and attitudes that had kept the feeling(s) repressed to that part of the body, the tumor first softened and then disappeared, presumably by apoptosis. We believe that the consciousness-based/holistic medical toolbox has a serious additional offer to cancer patients, and we will therefore strongly encourage the scientific society to

  8. What does the British public think about human-animal hybrid embryos?

    PubMed

    Jones, David A

    2009-03-01

    In the recent UK debate on the Human Fertilisation and Embryology Bill, there have been conflicting claims about the extent of public support for, or opposition to, human-animal hybrids. Self-selecting polls tend to show opposition to hybrids. Representative-sample polling shows spontaneous opposition but can elicit conditional approval of research, combined with underlying unease. Public opinion is very finely divided, with people generally opposed to this research unless it is likely to lead to medical advances.

  9. Interest Inventory Items as Attitude Eliciting Stimuli in Classical Conditioning: A Test of the A-R-D Theory. Language, Personality, and Cross-Cultural Study and Measurement of the Human A-R-D (Motivational) System.

    ERIC Educational Resources Information Center

    Gross, Michael C.; Staats, Arthur W.

    An experiment was conducted to test the hypothesis that interest inventory items elicit classically conditionable attitudinal responses. A higher-order conditioning procedure was used in which items from the Strong Vocational Interest Blank were employed as unconditioned stimuli and nonsense syllables as conditioned stimuli. Items for which the…

  10. The biological control of voluntary exercise, spontaneous physical activity and daily energy expenditure in relation to obesity: human and rodent perspectives

    PubMed Central

    Garland, Theodore; Schutz, Heidi; Chappell, Mark A.; Keeney, Brooke K.; Meek, Thomas H.; Copes, Lynn E.; Acosta, Wendy; Drenowatz, Clemens; Maciel, Robert C.; van Dijk, Gertjan; Kotz, Catherine M.; Eisenmann, Joey C.

    2011-01-01

    Mammals expend energy in many ways, including basic cellular maintenance and repair, digestion, thermoregulation, locomotion, growth and reproduction. These processes can vary tremendously among species and individuals, potentially leading to large variation in daily energy expenditure (DEE). Locomotor energy costs can be substantial for large-bodied species and those with high-activity lifestyles. For humans in industrialized societies, locomotion necessary for daily activities is often relatively low, so it has been presumed that activity energy expenditure and DEE are lower than in our ancestors. Whether this is true and has contributed to a rise in obesity is controversial. In humans, much attention has centered on spontaneous physical activity (SPA) or non-exercise activity thermogenesis (NEAT), the latter sometimes defined so broadly as to include all energy expended due to activity, exclusive of volitional exercise. Given that most people in Western societies engage in little voluntary exercise, increasing NEAT may be an effective way to maintain DEE and combat overweight and obesity. One way to promote NEAT is to decrease the amount of time spent on sedentary behaviours (e.g. watching television). The effects of voluntary exercise on other components of physical activity are highly variable in humans, partly as a function of age, and have rarely been studied in rodents. However, most rodent studies indicate that food consumption increases in the presence of wheels; therefore, other aspects of physical activity are not reduced enough to compensate for the energetic cost of wheel running. Most rodent studies also show negative effects of wheel access on body fat, especially in males. Sedentary behaviours per se have not been studied in rodents in relation to obesity. Several lines of evidence demonstrate the important role of dopamine, in addition to other neural signaling networks (e.g. the endocannabinoid system), in the control of voluntary exercise. A

  11. Effect of in vitro irradiation and cell cycle-inhibitory drugs on the spontaneous human IgE synthesis in vitro

    SciTech Connect

    Del Prete, G.F.; Vercelli, D.; Tiri, A.; Maggi, E.; Rossi, O.; Romagnani, S.; Ricci, M.

    1987-01-01

    The in vitro effects of radiation, diterpine forskolin (FK), and hydrocortisone (HC) on the in vitro spontaneous IgE synthesis by peripheral blood B-lymphocytes from atopic patients were investigated. Without affecting cell viability, in vitro irradiation inhibited in a dose-dependent fashion de novo IgE synthesis in vitro by B cells from all patients examined with a mean 40% reduction of in vitro IgE product after treatment with 100 rads. In contrast, the in vitro IgE production by the U266 myeloma cell line was unaffected, even by irradiation with 1600 rads. The addition to B cell cultures from atopic patients of FK consistently resulted in a dose-dependent inhibition of the spontaneous IgE production in vitro. The addition to cultures of 10(-5) and 10(-6) molar concentrations of HC was also usually inhibitory, whereas lower HC concentrations were uneffective or even enhanced the spontaneous in vitro IgE synthesis. When 10(-6) molar concentrations of both HC and FK were combined in culture, a summation inhibitory effect on the spontaneous IgE synthesis was observed. In contrast, neither FK nor HC had inhibitory effect on the in vitro spontaneous IgE synthesis by the U266 myeloma cell line. The spontaneous in vitro IgE synthesis by B cells from patients with Hodgkin's disease, demonstrating high levels of serum IgE, was strongly reduced or virtually abolished after patients underwent total nodal irradiation to prevent the spread of the disease. In addition, the in vitro spontaneous IgE synthesis by B cells from atopic patients was markedly decreased or abolished by in vivo administration of betamethasone.

  12. An FMRI investigation of spontaneous mental state inference for moral judgment.

    PubMed

    Young, Liane; Saxe, Rebecca

    2009-07-01

    Human moral judgment depends critically on "theory of mind," the capacity to represent the mental states of agents. Recent studies suggest that the right TPJ (RTPJ) and, to lesser extent, the left TPJ (LTPJ), the precuneus (PC), and the medial pFC (MPFC) are robustly recruited when participants read explicit statements of an agent's beliefs and then judge the moral status of the agent's action. Real-world interactions, by contrast, often require social partners to infer each other's mental states. The current study uses fMRI to probe the role of these brain regions in supporting spontaneous mental state inference in the service of moral judgment. Participants read descriptions of a protagonist's action and then either (i) "moral" facts about the action's effect on another person or (ii) "nonmoral" facts about the situation. The RTPJ, PC, and MPFC were recruited selectively for moral over nonmoral facts, suggesting that processing moral stimuli elicits spontaneous mental state inference. In a second experiment, participants read the same scenarios, but explicit statements of belief preceded the facts: Protagonists believed their actions would cause harm or not. The response in the RTPJ, PC, and LTPJ was again higher for moral facts but also distinguished between neutral and negative outcomes. Together, the results illuminate two aspects of theory of mind in moral judgment: (1) spontaneous belief inference and (2) stimulus-driven belief integration. PMID:18823250

  13. Frequencies of spontaneous breast development and spontaneous menarche in Turner syndrome in Japan.

    PubMed

    Tanaka, Toshiaki; Igarashi, Yutaka; Ozono, Keiichi; Ohyama, Kenji; Ogawa, Masamichi; Osada, Hisao; Onigata, Kazumichi; Kanzaki, Susumu; Kohno, Hitoshi; Seino, Yoshiki; Takahashi, Hiroaki; Tajima, Toshihiro; Tachibana, Katsuhiko; Tanaka, Hiroyuki; Nishi, Yoshikazu; Hasegawa, Tomonobu; Fujita, Keinosuke; Yorifuji, Tohru; Horikawa, Reiko; Yokoya, Susumu

    2015-10-01

    The Growject® database on human GH treatment in Turner syndrome was analyzed in the Turner Syndrome Research Collaboration, and the relationships of the frequencies of spontaneous breast development and spontaneous menarche with karyotype and GH treatment were investigated. One hundred and three cases started GH treatment with 0.5 IU/kg/ week (0.5 IU group), and their dose was increased to 0.35 mg/kg/wk midway through the treatment course. Another 109 cases started GH at a dose of 0.35 mg/kg/wk (0.35 mg group). Spontaneous breast development was observed in 77 (36.3%) of the 212 patients, and spontaneous menarche occurred in 31 patients (14.6%). The frequency of spontaneous breast development was significantly lower in patients with the 45,X karyotype and significantly higher in patients with a structural abnormality of the second X chromosome. The frequency of spontaneous menarche was significantly higher in patients with mosaicism characterized by X monosomy and a cellular line with no structural abnormality of the X chromosome. No significant differences in frequencies of spontaneous breast development and spontaneous menarche were observed between the two dose groups, indicating that GH treatment does not increase the frequency of spontaneous puberty.

  14. Frequencies of spontaneous breast development and spontaneous menarche in Turner syndrome in Japan.

    PubMed

    Tanaka, Toshiaki; Igarashi, Yutaka; Ozono, Keiichi; Ohyama, Kenji; Ogawa, Masamichi; Osada, Hisao; Onigata, Kazumichi; Kanzaki, Susumu; Kohno, Hitoshi; Seino, Yoshiki; Takahashi, Hiroaki; Tajima, Toshihiro; Tachibana, Katsuhiko; Tanaka, Hiroyuki; Nishi, Yoshikazu; Hasegawa, Tomonobu; Fujita, Keinosuke; Yorifuji, Tohru; Horikawa, Reiko; Yokoya, Susumu

    2015-10-01

    The Growject® database on human GH treatment in Turner syndrome was analyzed in the Turner Syndrome Research Collaboration, and the relationships of the frequencies of spontaneous breast development and spontaneous menarche with karyotype and GH treatment were investigated. One hundred and three cases started GH treatment with 0.5 IU/kg/ week (0.5 IU group), and their dose was increased to 0.35 mg/kg/wk midway through the treatment course. Another 109 cases started GH at a dose of 0.35 mg/kg/wk (0.35 mg group). Spontaneous breast development was observed in 77 (36.3%) of the 212 patients, and spontaneous menarche occurred in 31 patients (14.6%). The frequency of spontaneous breast development was significantly lower in patients with the 45,X karyotype and significantly higher in patients with a structural abnormality of the second X chromosome. The frequency of spontaneous menarche was significantly higher in patients with mosaicism characterized by X monosomy and a cellular line with no structural abnormality of the X chromosome. No significant differences in frequencies of spontaneous breast development and spontaneous menarche were observed between the two dose groups, indicating that GH treatment does not increase the frequency of spontaneous puberty. PMID:26568657

  15. Frequencies of spontaneous breast development and spontaneous menarche in Turner syndrome in Japan

    PubMed Central

    Tanaka, Toshiaki; Igarashi, Yutaka; Ozono, Keiichi; Ohyama, Kenji; Ogawa, Masamichi; Osada, Hisao; Onigata, Kazumichi; Kanzaki, Susumu; Kohno, Hitoshi; Seino, Yoshiki; Takahashi, Hiroaki; Tajima, Toshihiro; Tachibana, Katsuhiko; Tanaka, Hiroyuki; Nishi, Yoshikazu; Hasegawa, Tomonobu; Fujita, Keinosuke; Yorifuji, Tohru; Horikawa, Reiko; Yokoya, Susumu

    2015-01-01

    Abstract. The Growject® database on human GH treatment in Turner syndrome was analyzed in the Turner Syndrome Research Collaboration, and the relationships of the frequencies of spontaneous breast development and spontaneous menarche with karyotype and GH treatment were investigated. One hundred and three cases started GH treatment with 0.5 IU/kg/ week (0.5 IU group), and their dose was increased to 0.35 mg/kg/wk midway through the treatment course. Another 109 cases started GH at a dose of 0.35 mg/kg/wk (0.35 mg group). Spontaneous breast development was observed in 77 (36.3%) of the 212 patients, and spontaneous menarche occurred in 31 patients (14.6%). The frequency of spontaneous breast development was significantly lower in patients with the 45,X karyotype and significantly higher in patients with a structural abnormality of the second X chromosome. The frequency of spontaneous menarche was significantly higher in patients with mosaicism characterized by X monosomy and a cellular line with no structural abnormality of the X chromosome. No significant differences in frequencies of spontaneous breast development and spontaneous menarche were observed between the two dose groups, indicating that GH treatment does not increase the frequency of spontaneous puberty. PMID:26568657

  16. Spontaneous pneumothorax during pregnancy.

    PubMed

    Gorospe, Luis; Puente, Susana; Madrid, Carmen; Novo, Susana; Gil-Alonso, José L; Guntiñas, Alicia

    2002-05-01

    Spontaneous pneumothorax complicating pregnancy is rare. Only 41 cases have been previously published. We describe a case of spontaneous pneumothorax successfully treated with tube thoracostomy during the 38th week of pregnancy. Under epidural anesthesia, the patient had vaginal delivery of a healthy male infant 36 hours after tube thoracostomy.

  17. Simplified Expert Elicitation Procedure for Risk Assessment of Operating Events

    SciTech Connect

    Ronald L. Boring; David Gertman; Jeffrey Joe; Julie Marble; William Galyean; Larry Blackwood; Harold Blackman

    2005-06-01

    This report describes a simplified, tractable, and usable procedure within the US Nuclear Regulator Commission (NRC) for seeking expert opinion and judgment. The NRC has increased efforts to document the reliability and risk of nuclear power plants (NPPs) through Probabilistic Risk Assessment (PRA) and Human Reliability Analysis (HRA) models. The Significance Determination Process (SDP) and Accident Sequence Precursor (ASP) programs at the NRC utilize expert judgment on the probability of failure, human error, and the operability of equipment in cases where otherwise insufficient operational data exist to make meaningful estimates. In the past, the SDP and ASP programs informally sought the opinion of experts inside and outside the NRC. This document represents a formal, documented procedure to take the place of informal expert elicitation. The procedures outlined in this report follow existing formal expert elicitation methodologies, but are streamlined as appropriate to the degree of accuracy required and the schedule for producing SDP and ASP analyses.

  18. Are Hemianopic Reading and Visual Exploration Impairments Visually Elicited? New Insights from Eye Movements in Simulated Hemianopia

    ERIC Educational Resources Information Center

    Schuett, Susanne; Kentridge, Robert W.; Zihl, Josef; Heywood, Charles A.

    2009-01-01

    Hemianopic reading and visual exploration impairments are well-known clinical phenomena. Yet, it is unclear whether they are primarily caused by the hemianopic visual field defect itself or by additional brain injury preventing efficient spontaneous oculomotor adaptation. To establish the extent to which these impairments are visually elicited we…

  19. Basic emotions elicited by odors and pictures.

    PubMed

    Croy, Ilona; Olgun, Selda; Joraschky, Peter

    2011-12-01

    The sense of olfaction is often reported to have a special relationship with emotional processing. Memories triggered by olfactory cues often have a very emotional load. On the other hand, basic negative or positive emotional states should be sufficient to cover the most significant functions of the olfactory system including ingestion, hazard avoidance, and social communication. Thus, we investigated whether different basic emotions can be evoked in healthy people through the sense of olfaction. We asked 119 participants which odor evokes one of the six basic emotions (happiness, disgust, anger, anxiety, sadness, and surprise); another 97 participants were asked about pictures evoking those emotions. The results showed that almost every participant could name an olfactory elicitor for happiness or disgust. Olfactory elicitors of anxiety were reported less frequently, but they were still reported by three-quarters of the participants. However, for sadness and anger only about half of the participants reported an olfactory elicitor, whereas significantly more named a visual cue. Olfactory emotion elicitors were mainly related to the classes of culture, plants, and food, and visual emotion elicitors were largely related to humans. This data supports the hypothesis that in the vast majority of people, few differentiated emotions can be elicited through the olfactory channel. These emotions are happiness, disgust, and anxiety.

  20. Immunization with Ty21a live oral typhoid vaccine elicits crossreactive multifunctional CD8+ T-cell responses against Salmonella enterica serovar Typhi, S. Paratyphi A, and S. Paratyphi B in humans.

    PubMed

    Wahid, R; Fresnay, S; Levine, M M; Sztein, M B

    2015-11-01

    Previously we have extensively characterized Salmonella enterica serovar Typhi (S. Typhi)-specific cell-mediated immune (CMI) responses in volunteers orally immunized with the licensed Ty21a typhoid vaccine. In this study we measured Salmonella-specific multifunctional (MF) CD8+ T-cell responses to further investigate whether Ty21a elicits crossreactive CMI against S. Paratyphi A and S. Paratyphi B that also cause enteric fever. Ty21a-elicited crossreactive CMI responses against all three Salmonella serotypes were predominantly observed in CD8+ T effector/memory (T(EM)) and, to a lesser extent, in CD8+CD45RA+ T(EM) (T(EMRA)) subsets. These CD8+ T-cell responses were largely mediated by MF cells coproducing interferon-γ and macrophage inflammatory protein-1β and expressing CD107a with or without tumor necrosis factor-α. Significant proportions of Salmonella-specific MF cells expressed the gut-homing molecule integrin α4β7. In most subjects, similar MF responses were observed to S. Typhi and S. Paratyphi B, but not to S. Paratyphi A. These results suggest that Ty21a elicits MF CMI responses against Salmonella that could be critical in clearing the infection. Moreover, because S. Paratyphi A is a major public concern and Ty21a was shown in field studies not to afford cross-protection to S. Paratyphi A, these results will be important in developing a S. Typhi/S. Paratyphi A bivalent vaccine against enteric fevers.

  1. Cultural Differences and Students' Spontaneous Models of the Water Cycle: A Case Study of Jewish and Bedouin Children in Israel

    ERIC Educational Resources Information Center

    Ben-Zvi Assaraf, Orit; Eshach, Haim; Orion, Nir; Alamour, Yousif

    2012-01-01

    The present research aims at pinpointing differences in spontaneous and non-spontaneous mental models of water cycle conceptions of two 4th grade student groups: the Jewish residents of a small provincial town and a group of students from an indigenous Bedouin community. Students' conceptions were elicited using the Repertory Grid technique as…

  2. Lunar Cycle Influences Spontaneous Delivery in Cows.

    PubMed

    Yonezawa, Tomohiro; Uchida, Mona; Tomioka, Michiko; Matsuki, Naoaki

    2016-01-01

    There is a popular belief that the lunar cycle influences spontaneous delivery in both humans and cattle. To assess this relationship, we investigated the synodic distribution of spontaneous deliveries in domestic Holstein cows. We used retrospective data from 428 spontaneous, full-term deliveries within a three-year period derived from the calving records of a private farm in Hokkaido, Japan. Spontaneous birth frequency increased uniformly from the new moon to the full moon phase and decreased until the waning crescent phase. There was a statistically significant peak between the waxing gibbous and full moon phases compared with those between the last quarter and the waning crescent. These changes were clearly observed in deliveries among multiparous cows, whereas they were not evident in deliveries among nulliparous cows. These data suggest the utility of dairy cows as models for bio-meteorological studies, and indicate that monitoring lunar phases may facilitate comprehensive understanding of parturition. PMID:27580019

  3. Lunar Cycle Influences Spontaneous Delivery in Cows

    PubMed Central

    Yonezawa, Tomohiro; Uchida, Mona; Tomioka, Michiko; Matsuki, Naoaki

    2016-01-01

    There is a popular belief that the lunar cycle influences spontaneous delivery in both humans and cattle. To assess this relationship, we investigated the synodic distribution of spontaneous deliveries in domestic Holstein cows. We used retrospective data from 428 spontaneous, full-term deliveries within a three-year period derived from the calving records of a private farm in Hokkaido, Japan. Spontaneous birth frequency increased uniformly from the new moon to the full moon phase and decreased until the waning crescent phase. There was a statistically significant peak between the waxing gibbous and full moon phases compared with those between the last quarter and the waning crescent. These changes were clearly observed in deliveries among multiparous cows, whereas they were not evident in deliveries among nulliparous cows. These data suggest the utility of dairy cows as models for bio-meteorological studies, and indicate that monitoring lunar phases may facilitate comprehensive understanding of parturition. PMID:27580019

  4. Spontaneous combustion of hydrogen

    NASA Technical Reports Server (NTRS)

    Nusselt, Wilhelm; Pothmann, PH

    1923-01-01

    It is shown by the author's experiments that hydrogen which escapes to the atmosphere through openings in the system may burn spontaneously if it contains dust. Purely thermal reasoning can not account for the combustion. It seems to be rather an electrical ignition. In order to determine whether the cause of the spontaneous ignition was thermo-chemical, thermo-mechanical, or thermo-electrical, the experiments in this paper were performed.

  5. Spontaneous cholecystocutaneous abscess.

    PubMed

    Metsemakers, W J; Quanten, I; Vanhoenacker, F; Spiessens, T

    2010-01-01

    Spontaneous cholecystocutaneous abscesses or fistulae are rare complications of neglected biliary calculous disease which have become extremely rare during the last decades. We report a case of spontaneous cholecystocutaneous abscess in a 69-year-old male who presented with a mass in the right subcostal region.The diagnosis was made by CT scan with multiplanar reformating. Treatment consisted of incision and drainage of the abdominal wall abscess followed by cholecystectomy in a one-stage protocol.

  6. Stereoscopy Amplifies Emotions Elicited by Facial Expressions

    PubMed Central

    Kätsyri, Jari; Häkkinen, Jukka

    2015-01-01

    Mediated facial expressions do not elicit emotions as strongly as real-life facial expressions, possibly due to the low fidelity of pictorial presentations in typical mediation technologies. In the present study, we investigated the extent to which stereoscopy amplifies emotions elicited by images of neutral, angry, and happy facial expressions. The emotional self-reports of positive and negative valence (which were evaluated separately) and arousal of 40 participants were recorded. The magnitude of perceived depth in the stereoscopic images was manipulated by varying the camera base at 15, 40, 65, 90, and 115 mm. The analyses controlled for participants’ gender, gender match, emotional empathy, and trait alexithymia. The results indicated that stereoscopy significantly amplified the negative valence and arousal elicited by angry expressions at the most natural (65 mm) camera base, whereas stereoscopy amplified the positive valence elicited by happy expressions in both the narrowed and most natural (15–65 mm) base conditions. Overall, the results indicate that stereoscopy amplifies the emotions elicited by mediated emotional facial expressions when the depth geometry is close to natural. The findings highlight the sensitivity of the visual system to depth and its effect on emotions. PMID:27551358

  7. Stereoscopy Amplifies Emotions Elicited by Facial Expressions.

    PubMed

    Hakala, Jussi; Kätsyri, Jari; Häkkinen, Jukka

    2015-12-01

    Mediated facial expressions do not elicit emotions as strongly as real-life facial expressions, possibly due to the low fidelity of pictorial presentations in typical mediation technologies. In the present study, we investigated the extent to which stereoscopy amplifies emotions elicited by images of neutral, angry, and happy facial expressions. The emotional self-reports of positive and negative valence (which were evaluated separately) and arousal of 40 participants were recorded. The magnitude of perceived depth in the stereoscopic images was manipulated by varying the camera base at 15, 40, 65, 90, and 115 mm. The analyses controlled for participants' gender, gender match, emotional empathy, and trait alexithymia. The results indicated that stereoscopy significantly amplified the negative valence and arousal elicited by angry expressions at the most natural (65 mm) camera base, whereas stereoscopy amplified the positive valence elicited by happy expressions in both the narrowed and most natural (15-65 mm) base conditions. Overall, the results indicate that stereoscopy amplifies the emotions elicited by mediated emotional facial expressions when the depth geometry is close to natural. The findings highlight the sensitivity of the visual system to depth and its effect on emotions. PMID:27551358

  8. Stereoscopy Amplifies Emotions Elicited by Facial Expressions.

    PubMed

    Hakala, Jussi; Kätsyri, Jari; Häkkinen, Jukka

    2015-12-01

    Mediated facial expressions do not elicit emotions as strongly as real-life facial expressions, possibly due to the low fidelity of pictorial presentations in typical mediation technologies. In the present study, we investigated the extent to which stereoscopy amplifies emotions elicited by images of neutral, angry, and happy facial expressions. The emotional self-reports of positive and negative valence (which were evaluated separately) and arousal of 40 participants were recorded. The magnitude of perceived depth in the stereoscopic images was manipulated by varying the camera base at 15, 40, 65, 90, and 115 mm. The analyses controlled for participants' gender, gender match, emotional empathy, and trait alexithymia. The results indicated that stereoscopy significantly amplified the negative valence and arousal elicited by angry expressions at the most natural (65 mm) camera base, whereas stereoscopy amplified the positive valence elicited by happy expressions in both the narrowed and most natural (15-65 mm) base conditions. Overall, the results indicate that stereoscopy amplifies the emotions elicited by mediated emotional facial expressions when the depth geometry is close to natural. The findings highlight the sensitivity of the visual system to depth and its effect on emotions.

  9. Crows spontaneously exhibit analogical reasoning.

    PubMed

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training.

  10. Crows spontaneously exhibit analogical reasoning.

    PubMed

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. PMID:25532894

  11. Biomodal spontaneous fission

    SciTech Connect

    Hulet, E.K. )

    1989-09-26

    Investigations of mass and kinetic-energy distributions from spontaneous fission have been extended in recent years to an isotope of element 104 and, for half-lives, to an isotope of element 108. The results have been surprising in that spontaneous fission half-lives have turned out to be much longer than expected and mass and kinetic- energy distributions were found to abruptly shift away from those of the lighter actinides, showing two modes of fission. These new developments have caused a re-evaluation of our understanding of the fission process, bringing an even deeper appreciation of the role played by nuclear shell effects upon spontaneous fission properties. 16 refs., 10 figs.

  12. Spontaneous sarcomere dynamics

    NASA Astrophysics Data System (ADS)

    Günther, Stefan; Kruse, Karsten

    2010-12-01

    Sarcomeres are the basic force generating units of striated muscles and consist of an interdigitating arrangement of actin and myosin filaments. While muscle contraction is usually triggered by neural signals, which eventually set myosin motors into motion, isolated sarcomeres can oscillate spontaneously between a contracted and a relaxed state. We analyze a model for sarcomere dynamics, which is based on a force-dependent detachment rate of myosin from actin. Our numerical bifurcation analysis of the spontaneous sarcomere dynamics reveals notably Hopf bifurcations, canard explosions, and gluing bifurcations. We discuss possible implications for experiments.

  13. Studying brain organization via spontaneous fMRI signal.

    PubMed

    Power, Jonathan D; Schlaggar, Bradley L; Petersen, Steven E

    2014-11-19

    In recent years, some substantial advances in understanding human (and nonhuman) brain organization have emerged from a relatively unusual approach: the observation of spontaneous activity, and correlated patterns in spontaneous activity, in the "resting" brain. Most commonly, spontaneous neural activity is measured indirectly via fMRI signal in subjects who are lying quietly in the scanner, the so-called "resting state." This Primer introduces the fMRI-based study of spontaneous brain activity, some of the methodological issues active in the field, and some ways in which resting-state fMRI has been used to delineate aspects of area-level and supra-areal brain organization.

  14. Familial spontaneous pneumothorax in three generations and its HLA.

    PubMed

    Yamada, Akitoshi; Takeda, Yoshitaka; Hayashi, Satoru; Shimizu, Kazuta

    2003-09-01

    We experienced a case of familial spontaneous pneumothorax in three generations. Six of 13 family members had episodes of spontaneous pneumothorax. It is well established that there are some diseases associated with human leukocyte antigen (HLA). We performed HLA phenotyping for HLA of A, B and C. In our study, we detected the HLA haplotype A2, B61 in three of 4 who had episodes of spontaneous pneumothorax. The HLA haplotype A2, B70 were also detected in three of 4 who had episodes. This suggests that familial spontaneous pneumothorax might have hereditary factors.

  15. Comparison of the performance of two spontaneous sedimentation techniques for the diagnosis of human intestinal parasites in the absence of a gold standard.

    PubMed

    Gonçalves, Alessandra Queiroga; Abellana, Rosa; Pereira-da-Silva, Hélio Doyle; Santos, Ivanildes; Serra, Paula Taquita; Julião, Genimar Rebouças; Orlandi, Patricia Puccinelli; Ascaso, Carlos

    2014-03-01

    Performance evaluation of diagnostic tests is critical in the search for accurate diagnoses. A gold standard test is usually absent in parasitology, thus rendering satisfactory assessment of diagnostic accuracy difficult. Moreover, reliability (assessed by the study of repeatability) is a rarely studied characteristic of diagnostic tests. This study compared and evaluated the performance (repeatability, concordance and accuracy) of the spontaneous sedimentation technique (SST) and the Paratest for the diagnosis of Giardia lamblia, Entamoeba histolytica complex, Blastocystis spp., Ascaris lumbricoides, hookworm, Trichuris trichiura and Calodium hepaticum. Fecal samples of 143 individuals were separated into three replicates for each test. Concordance and homogeneity of the results between replicates of each test and between tests were evaluated. Proportions of positives, sensitivity and specificity were estimated using a Bayesian Latent Class Model. High repeatability of both tests was found for the detection of intestinal parasites, except for Blastocystis spp. and hookworm. Concordance between tests was generally high (concordance correlation coefficient, 0.72-0.88), except for Blastocystis spp., hookworm and T. trichiura. The Paratest detected more cases of Blastocystis spp. and fewer of hookworm than the SST. The tests were quite discordant in the detection of T. trichiura. A low sensitivity (39.4-49.2% for SST, 35.8-53.8% for Paratest) and a high specificity (93.2-97.2%) were found for both tests. The Paratest presented a slightly higher sensitivity for the diagnosis of Blastocystis spp. (53.8%), and SST did so for hookworm (49.2%). This is the first study on repeatability and accuracy (using a Bayesian approach) of two spontaneous sedimentation techniques. These results suggest underdiagnosis of little dense parasitic forms due to technical limitations in both tests. We conclude that the combined study of repeatability, concordance and accuracy is a key

  16. Characterization of the subsets of human NKT-like cells and the expression of Th1/Th2 cytokines in patients with unexplained recurrent spontaneous abortion.

    PubMed

    Yuan, Jing; Li, Jian; Huang, Shi-Yun; Sun, Xin

    2015-08-01

    The objective was to investigate the subsets of natural killer T (NKT)-like cells and the expression of Th1/Th2 cytokines in the peripheral blood (PB) and/or decidual tissue of patients with unexplained recurrent spontaneous abortion (URSA). The percentages of NKT-like cells in the PB and deciduas of URSA patients in early pregnancy and in the PB of nonpregnant women were analyzed by flow cytometry. The expression of interferon (IFN)-γ (Th1 cytokine) and Th2 cytokines, interleukin (IL)-4 and IL-10, in the PB and decidual tissue was measured by quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA). Most percentages of subsets of NKT-like cells (CD3(+)CD56(+), CD3(+)CD56(+)CD16(+)) in the PB and deciduas were significantly greater in URSA patients than in normal pregnant and nonpregnant women. A cut-off value of 3.75% for the increased percentage of CD3(+)CD56(+)CD16(+) NKT-like cells in the PB appeared to be predictive of pregnancy failure. Moreover, we found that in the decidua, IFN-γ expression was significantly higher, while IL-4 and IL-10 expression was significantly lower in URSA patients compared with those with a normal pregnancy. The ratio of decidual Th1/Th2 cytokines in URSA patients was significantly increased compared with that in normal pregnant women. Decidual IL-4 expression correlated negatively with the percentages of blood CD3(+)CD56(+)CD16(+) NKT-like cells and the decidual CD3(+)CD56(+) and CD3(+)CD56(+)CD16(+) NKT-like cells. NKT-like cells may play an important role in maintaining normal pregnancy. Measurement of CD3(+)CD56(+)CD16(+) NKT-like cells in the PB may provide a potential tool for assessing patients' risk of spontaneous abortion.

  17. Fast Sequences of Non-spatial State Representations in Humans.

    PubMed

    Kurth-Nelson, Zeb; Economides, Marcos; Dolan, Raymond J; Dayan, Peter

    2016-07-01

    Fast internally generated sequences of neural representations are suggested to support learning and online planning. However, these sequences have only been studied in the context of spatial tasks and never in humans. Here, we recorded magnetoencephalography (MEG) while human subjects performed a novel non-spatial reasoning task. The task required selecting paths through a set of six visual objects. We trained pattern classifiers on the MEG activity elicited by direct presentation of the visual objects alone and tested these classifiers on activity recorded during periods when no object was presented. During these object-free periods, the brain spontaneously visited representations of approximately four objects in fast sequences lasting on the order of 120 ms. These sequences followed backward trajectories along the permissible paths in the task. Thus, spontaneous fast sequential representation of states can be measured non-invasively in humans, and these sequences may be a fundamental feature of neural computation across tasks. PMID:27321922

  18. Distinguishing Between Social Reinforcement and Social Elicitation.

    ERIC Educational Resources Information Center

    Bloom, Kathleen

    1984-01-01

    Discusses the distinction between species-typical (elicitation) and operant reinforcement interpretations of infant/adult social interaction; considers procedural and analytic components of Poulson's 1983 paper (v36 p471-89); and clarifies differences in Poulson's interpretation and the author's interpretation of the vocal conditioning studies of…

  19. Eliciting User Requirements Using Appreciative Inquiry

    ERIC Educational Resources Information Center

    Gonzales, Carol Kernitzki

    2010-01-01

    Many software development projects fail because they do not meet the needs of users, are over-budget, and abandoned. To address this problem, the user requirements elicitation process was modified based on principles of Appreciative Inquiry. Appreciative Inquiry, commonly used in organizational development, aims to build organizations, processes,…

  20. 'Goats that stare at men': dwarf goats alter their behaviour in response to human head orientation, but do not spontaneously use head direction as a cue in a food-related context.

    PubMed

    Nawroth, Christian; von Borell, Eberhard; Langbein, Jan

    2015-01-01

    Recently, comparative research on the mechanisms and species-specific adaptive values of attributing attentive states and using communicative cues has gained increased interest, particularly in non-human primates, birds, and dogs. Here, we investigate these phenomena in a farm animal species, the dwarf goat (Capra aegagrus hircus). In the first experiment, we investigated the effects of different human head and body orientations, as well as human experimenter presence/absence, on the behaviour of goats in a food-anticipating paradigm. Over a 30-s interval, the experimenter engaged in one of four different postures or behaviours (head and body towards the subject-'Control', head to the side, head and body away from the subject, or leaving the room) before delivering a reward. We found that the level of subjects' active anticipatory behaviour was highest in the control condition and decreased with a decreasing level of attention paid to the subject by the experimenter. Additionally, goats 'stared' (i.e. stood alert) at the experimental set-up for significantly more time when the experimenter was present but paid less attention to the subject ('Head' and 'Back' condition) than in the 'Control' and 'Out' conditions. In a second experiment, the experimenter provided different human-given cues that indicated the location of a hidden food reward in a two-way object choice task. Goats were able to use both 'Touch' and 'Point' cues to infer the correct location of the reward but did not perform above the level expected by chance in the 'Head only' condition. We conclude that goats are able to differentiate among different body postures of a human, including head orientation; however, despite their success at using multiple physical human cues, they fail to spontaneously use human head direction as a cue in a food-related context.

  1. Emotional expressions preferentially elicit implicit evaluations of faces also varying in race or age.

    PubMed

    Craig, Belinda M; Lipp, Ottmar V; Mallan, Kimberley M

    2014-10-01

    Both facial cues of group membership (race, age, and sex) and emotional expressions can elicit implicit evaluations to guide subsequent social behavior. There is, however, little research addressing whether group membership cues or emotional expressions are more influential in the formation of implicit evaluations of faces when both cues are simultaneously present. The current study aimed to determine this. Emotional expressions but not race or age cues elicited implicit evaluations in a series of affective priming tasks with emotional Caucasian and African faces (Experiments 1 and 2) and young and old faces (Experiment 3). Spontaneous evaluations of group membership cues of race and age only occurred when those cues were task relevant, suggesting the preferential influence of emotional expressions in the formation of implicit evaluations of others when cues of race or age are not salient. Implications for implicit prejudice, face perception, and person construal are discussed. PMID:25046242

  2. The 2009 pandemic H1N1 and triple-reassortant swine H1N1 influenza viruses replicate efficiently but elicit an attenuated inflammatory response in polarized human bronchial epithelial cells.

    PubMed

    Zeng, Hui; Pappas, Claudia; Katz, Jacqueline M; Tumpey, Terrence M

    2011-01-01

    The pandemic H1N1 virus of 2009 (2009 H1N1) produced a spectrum of disease ranging from mild illness to severe illness and death. Respiratory symptoms were frequently associated with virus infection, with relatively high rate of gastrointestinal symptoms reported. To better understand 2009 H1N1 virus pathogenesis in humans, we studied virus and host responses following infection of two cell types: polarized bronchial and pharyngeal epithelial cells, which exhibit many features of the human airway epithelium, and colon epithelial cells to serve as a human intestinal cell model. Selected 2009 H1N1 viruses were compared to both seasonal H1N1 and triple-reassortant swine H1N1 influenza viruses that have circulated among North American pigs since before the 2009 pandemic. All H1N1 viruses replicated productively in airway cells; however, in contrast to seasonal H1N1 virus infection, infection with the 2009 H1N1 and triple-reassortant swine H1N1 viruses resulted in an attenuated inflammatory response, a weaker interferon response, and reduced cell death. Additionally, the H1N1 viruses of swine origin replicated less efficiently at the temperature of the human proximal airways (33°C). We also observed that the 2009 H1N1 viruses replicated to significantly higher titers than seasonal H1N1 virus in polarized colon epithelial cells. These studies reveal that in comparison to seasonal influenza virus, H1N1 viruses of swine origin poorly activate multiple aspects of the human innate response, which may contribute to the virulence of these viruses. In addition, their less efficient replication at human upper airway temperatures has implications for the understanding of pandemic H1N1 virus adaptation to humans.

  3. Spontaneous periodic hypothermia.

    PubMed

    Kloos, R T

    1995-09-01

    Spontaneous periodic hypothermia is a rare syndrome of recurrent, centrally mediated hypothermia without an identifiable systemic cause or brain lesion. Most patients defend a temporarily lowered temperature "set point" during episodes of hypothermia, despite manifesting many well-known systemic consequences of core temperature hypothermia. No case of death directly attributable to an episode of spontaneous periodic hypothermia has been reported, although many of the serious systemic effects of hypothermia have been documented in these cases, so it is not unlikely that death may occur. The syndrome's cause, and that of Shapiro syndrome, remains unknown. Pharmacologic trials to date have been only modestly successful. Anticonvulsant agents, clonidine, and cyproheptadine appear the most likely to succeed, with cyproheptadine being a reasonable first choice. Given that the term "spontaneous periodic hypothermia" describes a syndrome, and not a pathophysiologic mechanism, it is likely to encompass a common eventuality, arrived at via several different pathways. One can postulate mechanisms such as structural abnormalities, trauma, infection, irritation, and degeneration involving strategic locations which create a focus for epileptic or other periodic dysfunction whose scope involves the centers for thermoregulation. The existence of 2 distinct, oppositional thermoregulatory centers would allow for speculation of similar mechanisms accounting for cases of both periodic hypo- and hyperthermia (61). Postmortem data regarding the hypothalamic and surrounding areas from future cases of Shapiro syndrome and spontaneous periodic hypothermia would be of great interest. Further, more sensitive in vivo testing methods are clearly needed. The role of PET or single photon emission computed tomography (SPECT) with technetium 99m-labeled hexamethylpropylene amine oxime (Tc 99m HMPAO) performed acutely during an episode remains to be characterized (64, 103, 105). The term

  4. Dreamed movement elicits activation in the sensorimotor cortex.

    PubMed

    Dresler, Martin; Koch, Stefan P; Wehrle, Renate; Spoormaker, Victor I; Holsboer, Florian; Steiger, Axel; Sämann, Philipp G; Obrig, Hellmuth; Czisch, Michael

    2011-11-01

    Since the discovery of the close association between rapid eye movement (REM) sleep and dreaming, much effort has been devoted to link physiological signatures of REM sleep to the contents of associated dreams [1-4]. Due to the impossibility of experimentally controlling spontaneous dream activity, however, a direct demonstration of dream contents by neuroimaging methods is lacking. By combining brain imaging with polysomnography and exploiting the state of "lucid dreaming," we show here that a predefined motor task performed during dreaming elicits neuronal activation in the sensorimotor cortex. In lucid dreams, the subject is aware of the dreaming state and capable of performing predefined actions while all standard polysomnographic criteria of REM sleep are fulfilled [5, 6]. Using eye signals as temporal markers, neural activity measured by functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) was related to dreamed hand movements during lucid REM sleep. Though preliminary, we provide first evidence that specific contents of REM-associated dreaming can be visualized by neuroimaging. PMID:22036177

  5. Dreamed movement elicits activation in the sensorimotor cortex.

    PubMed

    Dresler, Martin; Koch, Stefan P; Wehrle, Renate; Spoormaker, Victor I; Holsboer, Florian; Steiger, Axel; Sämann, Philipp G; Obrig, Hellmuth; Czisch, Michael

    2011-11-01

    Since the discovery of the close association between rapid eye movement (REM) sleep and dreaming, much effort has been devoted to link physiological signatures of REM sleep to the contents of associated dreams [1-4]. Due to the impossibility of experimentally controlling spontaneous dream activity, however, a direct demonstration of dream contents by neuroimaging methods is lacking. By combining brain imaging with polysomnography and exploiting the state of "lucid dreaming," we show here that a predefined motor task performed during dreaming elicits neuronal activation in the sensorimotor cortex. In lucid dreams, the subject is aware of the dreaming state and capable of performing predefined actions while all standard polysomnographic criteria of REM sleep are fulfilled [5, 6]. Using eye signals as temporal markers, neural activity measured by functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) was related to dreamed hand movements during lucid REM sleep. Though preliminary, we provide first evidence that specific contents of REM-associated dreaming can be visualized by neuroimaging.

  6. Serological evidence that activation of ubiquitous human herpesvirus-6 (HHV-6) plays a role in chronic idiopathic/spontaneous urticaria (CIU).

    PubMed

    Dreyfus, D H

    2016-02-01

    Acute infection with viral pathogens in the herpesviridae family can trigger acute urticaria, and reactivation of herpesviridae is associated with cutaneous urticarial-like syndromes such as drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS). Reactivation of latent herpesviridae has not been studied systematically in chronic idiopathic/spontaneous urticaria (CIU). This review proposes that CIU is an inflammatory disorder with autoimmune features (termed 'CVU' for chronic viral urticaria), based on serology consistent with the hypothesis that reactivation of a latent herpesvirus or -viruses may play a role in CIU. Serology obtained from a cohort of omalizumab (Xolair)-dependent patients with severe CIU was consistent with previous HHV-6 infection, persistent viral gene expression and replication. CIU patients also exhibited serological evidence of increased immune response to HHV-4 (Epstein-Barr virus, or EBV) but not all CIU patients were infected with EBV. These observations, combined with case reports of CIU response to anti-viral therapy, suggest that HHV-6, possibly interacting with HHV-4 in cutaneous tissues, is a candidate for further prospective study as a co-factor in CIU.

  7. Cognitive constraints on constituent order: Evidence from elicited pantomime

    PubMed Central

    Hall, Matthew L.; Mayberry, Rachel I.; Ferreira, Victor S.

    2014-01-01

    To what extent does human cognition influence the structure of human language? Recent experiments using elicited pantomime suggest that the prevalence of Subject-Object-Verb (SOV) order across the world's languages may arise in part because SOV order is most compatible with how we conceptually represent transitive events (Goldin-Meadow, So, Özyürek, & Mylander, 2008). However, this raises the question as to why non-SOV orders exist. Two recent studies (Meir, Lifshitz, Ilkbasaran, & Padden, 2010; Gibson et al., 2013) suggest that SOV might be suboptimal for describing events in which both the agent and patient are plausible agents (e.g. a woman pushing a boy); we call these “reversible” events. We replicate these findings using elicited pantomime and offer a new interpretation. Meir et al.'s (2010) account is framed largely in terms of constraints on comprehension, while Gibson et al.'s (2013) account involves minimizing the risk of information loss or memory degradation. We offer an alternative hypothesis that is grounded in constraints on production. We consider the implications of these findings for the distribution of constituent order in the world's spoken languages and for the structure of emerging sign languages. PMID:23792806

  8. Spontaneous ileostomy closure

    PubMed Central

    Alyami, Mohammad S.; Lundberg, Peter W.; Cotte, Eddy G.; Glehen, Olivier J.

    2016-01-01

    Iatrogenic ileostomies are routinely placed during colorectal surgery for the diversion of intestinal contents to permit healing of the distal anastomosis prior to elective reversal. We present an interesting case of spontaneous closure of a diverting ileostomy without any adverse effects to the patient. A 65-year-old woman, positive for hereditary non-polyposis colorectal cancer type-I, with locally invasive cancer of the distal colon underwent en-bloc total colectomy, hysterectomy, and bilateral salpingoophorectomy with creation of a proximal loop ileostomy. The ostomy temporarily closed without reoperation at 10 weeks, after spontaneously reopening, it definitively closed, again without surgical intervention at 18 weeks following the original surgery. This rare phenomenon has occurred following variable colorectal pathology and is poorly understood, particularly in patients with aggressive disease and adjunct perioperative interventions. PMID:27279518

  9. Spontaneous Transomental Hernia

    PubMed Central

    Lee, Seung Hun

    2016-01-01

    A transomental hernia through the greater or lesser omentum is rare, accounting for approximately 4% of internal hernias. Transomental hernias are generally reported in patients aged over fifty. In such instances, acquired transomental hernias are usual, are commonly iatrogenic, and result from surgical interventions or from trauma or peritoneal inflammation. In rare cases, such as the one described in this study, internal hernias through the greater or lesser omentum occur spontaneously as the result of senile atrophy without history of surgery, trauma, or inflammation. A transomental hernia has a high postoperative mortality rate of 30%, and emergency diagnosis and treatment are critical. We report a case of a spontaneous transomental hernia of the small intestine causing intestinal obstruction. An internal hernia with strangulation of the small bowel in the lesser sac was suspected from the image study. After an emergency laparotomy, a transomental hernia was diagnosed. PMID:26962535

  10. [Spontaneous bilateral Petit hernia].

    PubMed

    Fontoura, Rodrigo Dias; Araújo, Emerson Silveira de; Oliveira, Gustavo Alves de; Sarmenghi Filho, Deolindo; Kalil, Mitre

    2011-01-01

    Petit's lumbar hernia is an uncommon defect of the posterior abdominal wall that represents less than 1% of all abdominal wall hernias. It is more often unilateral and founded in young females, rarely containing a real herniated sac. There are two different approaches to repair: laparoscopy and open surgery. The goal of this article is to report one case of spontaneous bilateral lumbar Petit's hernia treated with open surgery.

  11. Essays on probability elicitation scoring rules

    NASA Astrophysics Data System (ADS)

    Firmino, Paulo Renato A.; dos Santos Neto, Ademir B.

    2012-10-01

    In probability elicitation exercises it has been usual to considerer scoring rules (SRs) to measure the performance of experts when inferring about a given unknown, Θ, for which the true value, θ*, is (or will shortly be) known to the experimenter. Mathematically, SRs quantify the discrepancy between f(θ) (the distribution reflecting the expert's uncertainty about Θ) and d(θ), a zero-one indicator function of the observation θ*. Thus, a remarkable characteristic of SRs is to contrast expert's beliefs with the observation θ*. The present work aims at extending SRs concepts and formulas for the cases where Θ is aleatory, highlighting advantages of goodness-of-fit and entropy-like measures. Conceptually, it is argued that besides of evaluating the personal performance of the expert, SRs may also play a role when comparing the elicitation processes adopted to obtain f(θ). Mathematically, it is proposed to replace d(θ) by g(θ), the distribution that model the randomness of Θ, and do also considerer goodness-of-fit and entropylike metrics, leading to SRs that measure the adherence of f(θ) to g(θ). The implications of this alternative perspective are discussed and illustrated by means of case studies based on the simulation of controlled experiments. The usefulness of the proposed approach for evaluating the performance of experts and elicitation processes is investigated.

  12. Expression of stage-specific embryonic antigen-4 (SSEA-4) defines spontaneous loss of epithelial phenotype in human solid tumor cells.

    PubMed

    Sivasubramaniyan, Kavitha; Harichandan, Abhishek; Schilbach, Karin; Mack, Andreas F; Bedke, Jens; Stenzl, Arnulf; Kanz, Lothar; Niederfellner, Gerhard; Bühring, Hans-Jörg

    2015-08-01

    Stage-specific embryonic antigen-4 (SSEA-4) is a glycosphingolipid, which is overexpressed in some cancers and has been linked to disease progression. However, little is known about the functions of SSEA-4 and the characteristics of SSEA-4 expressing tumor cells. Our studies identified SSEA-4 expression on a subpopulation of cells in many solid tumor cell lines but not in leukemic cell lines. Fluorescence-activated cell sorting-sorted SSEA-4(+) prostate cancer cells formed fibroblast-like colonies with limited cell-cell contacts, whereas SSEA-4(-) cells formed cobblestone-like epithelial colonies. Only colonies derived from SSEA-4(+) cells were enriched for pluripotent embryonic stem cell markers. Moreover, major epithelial cell-associated markers Claudin-7, E-cadherin, ESRP1 and GRHL2 were down-regulated in the SSEA-4(+) fraction of DU145 and HCT-116 cells. Similar to cell lines, SSEA-4(+) primary prostate tumor cells also showed down-regulation of epithelial cell-associated markers. In addition, they showed up-regulation of epithelial-to-mesenchymal transition as well as mesenchymal markers. Furthermore, SSEA-4(+) cells escape from adhesive colonies spontaneously and form invadopodia-like migratory structures, in which SSEA-4, cortactin as well as active pPI3K, pAkt and pSrc are enriched and colocalized. Finally, SSEA-4(+) cells displayed strong tumorigenic ability and stable knockdown of SSEA-4 synthesis resulted in decreased cellular adhesion to different extracellular matrices. In conclusion, we introduce SSEA-4 as a novel marker to identify heterogeneous, invasive subpopulations of tumor cells. Moreover, increased cell-surface SSEA-4 expression is associated with the loss of cell-cell interactions and the gain of a migratory phenotype, suggesting an important role of SSEA-4 in cancer invasion by influencing cellular adhesion to the extracellular matrix.

  13. Molecular mimicry and horror autotoxicus: do chlamydial infections elicit autoimmunity?

    PubMed

    Swanborg, Robert H; Boros, Dov L; Whittum-Hudson, Judith A; Hudson, Alan P

    2006-11-30

    All species of the order Chlamydiales are obligate intracellular eubacterial pathogens of their various hosts. Two chlamydial species, Chlamydia trachomatis and Chlamydia pneumoniae, are primarily human pathogens, and each is known to cause important diseases. Some strains of C. trachomatis are sexually transmitted and frequently cause severe reproductive problems, primarily in women. Other strains of the organism serve as the aetiological agents for blinding trachoma, still the leading cause of preventable blindness in underdeveloped nations. C. pneumoniae is a respiratory pathogen known to cause community-acquired pneumonia. Importantly, both organisms engender an immunopathogenic response in the human host, and both have been associated with widely diverse, relatively common and currently idiopathic chronic diseases, most of which include an important autoimmune component. In this article, we explore the available experimental data regarding the possible elicitation of autoimmunity in various contexts by chlamydial infection, and we suggest several avenues for research to explore this potentially important issue further.

  14. Epitope specificity of rabbit immunoglobulin G (IgG) elicited by pneumococcal type 23F synthetic oligosaccharide- and native polysaccharide-protein conjugate vaccines: comparison with human anti-polysaccharide 23F IgG.

    PubMed Central

    Alonso de Velasco, E; Verheul, A F; van Steijn, A M; Dekker, H A; Feldman, R G; Fernández, I M; Kamerling, J P; Vliegenthart, J F; Verhoef, J; Snippe, H

    1994-01-01

    Streptococcus pneumoniae type 23F capsular polysaccharide (PS23F) consitss of a repeating glycerol-phosphorylated branched tetrasaccharide. The immunogenicities of the following related antigens were investigated: (i) a synthetic trisaccharide comprising the backbone of one repeating unit, (ii) a synthetic tetrasaccharide comprising the complete repeating unit, and (iii) native PS23F (all three conjugated to keyhole limpet hemocyanin [KLH]) and (iv) formalin-killed S. pneumoniae 23F. All antigens except the trisaccharide-KLH conjugate induced relatively high anti-PS23F antibody levels in rabbits. The epitope specificity of such antibodies was then studied by means of an inhibition immunoassay. The alpha(1-->2)-linked L-rhamnose branch was shown to be immunodominant for immunoglobulin G (IgG) induced by tetrasaccharide-KLH, PS23F-KLH, and killed S. pneumoniae 23F: in most sera L-rhamnose totally inhibited the binding of IgG to PS23F. Thus, there appears to be no major difference in epitope specificity between IgG induced by tetrasaccharide-KLH and that induced by antigens containing the polymeric form of PS23F. Human anti-PS23F IgG (either vaccine induced or naturally acquired) had a different epitope specificity: none of the inhibitors used, including L-rhamnose and tetrasaccharide-KLH, exhibited substantial inhibition. These observations suggest that the epitope recognized by human IgG on PS23F is larger than the epitope recognized by rabbit IgG. Both human and rabbit antisera efficiently opsonized type 23F pneumococci, as measured in a phagocytosis assay using human polymorphonuclear leukocytes. PMID:7509318

  15. The novel C24D synthetic polypeptide inhibits binding of placenta immunosuppressive ferritin to human T cells and elicits anti-breast cancer immunity in vitro and in vivo.

    PubMed

    Solodeev, Inna; Zahalka, Muayad A; Moroz, Chaya

    2014-09-01

    Immune tolerance mechanisms supporting normal human pregnancy are exploited by breast cancer and other malignancies. We cloned from human placenta and breast cancer cells the novel human immunomodulator named placenta immunosuppressive ferritin (PLIF). PLIF is composed of a ferritin heavy chain-like domain and a novel cytokine-like domain, named C48. Both intact PLIF and C48 inhibit T cell proliferation. Blocking PLIF by specific antibodies in a tolerant breast cancer model in nude mice resulted in tumor cell apoptosis and rejection. This prompted us to study active immune preventive strategies targeting PLIF activity. Currently, we report on the design and synthesis of the novel C24D polypeptide, which inhibits the binding of PLIF to T cells and therefore inhibits the immune suppressive effect of PLIF. The effect of C24D on the generation of anti-breast cancer cytotoxic T lymphocytes (CTLs) was studied in vitro in cultures of MCF-7 (HLA-A2(+)) or T47D (HLA-A2(-)) breast cancer cells incubated with peripheral blood mononuclear cells (PBMCs) from healthy blood donors. We found that C24D treatment exclusively induced development of CTLs. On reactivation by their specific target cells, the CTLs secreted interferon-γ and induced target apoptosis. Anti-MCF-7 CTLs were cross-cytotoxic to MDA-MB-231 (HLA-A2(+)) triple-negative breast cancer but not to T47D. Moreover, C24D treatment in vivo inhibited the growth of MCF-7 tumors engrafted in immune-compromised nude mice transfused with naïve allogeneic human PBMCs. Our results demonstrate that C24D treatment breakdown breast cancer induced tolerance enabling the initiation of effective anti-tumor immune response. PMID:25246274

  16. Natural infection of baboons by Entamoeba histolytica elicits anti- gal-lectin heavy subunit IgA and IgG antibodies with shared epitope specificity to that of humans.

    PubMed

    Abd-Alla, Mohamed D; Wolf, Roman F; White, Gary L; Kosanke, Stanley D; Carey, David W; Verweij, Jaco J; El-Dessouky, Yasser M M; Zhang, Mie-Jie; Ravdin, Jonathan I

    2013-12-01

    Non-human primates, such as baboons (Papio hamadryas anubis), are natural hosts for Entamoeba species; infections can be asymptomatic or result in invasive lethal disease. It was sought to determine whether following natural infection by Entamoeba. histolytica, baboon anti-amebic antibodies recognized native Gallectin, a recombinant portion of the lectin heavy subunit (designated LC3) and specific heavy subunit epitopes; we compared the specificity of anti-amebic antibodies from baboons to that of humans following asymptomatic E. histolytica infection or cure of amebic liver abscess (ALA). Female baboons (n=54), aged one to three years of age and living in captivity were screened for infection by real time PCR. E. histolytica infection was found in 37 baboons and was associated with serum anti-LC3 IgG (73%) and anti-LC3 IgA (46%) or intestinal anti-Gal-Lectin IgA antibody responses (49%), p<0.021 for each compared to that observed with baboons having an E. dispar infection (n=10) or uninfected baboons (n=7). The ELISA OD reading for anti-LC3 or anti-lectin antibodies correlated strongly with the presence of a PCR CT value indicative of E. histolytica infection. In humans with asymptomatic E. histolytica infection or those recently cured of ALA, 63% and 57% had serum anti- LC3 IgA and 65% and 57% had serum anti-LC3 IgG antibodies respectively. Epitope- specific synthetic peptides were used as capture antigens in ELISA; for baboons that possessed anti-LC3 and anti-lectin antibodies, 74% had anti-peptide IgG or IgA antibodies, compared to 86% of asymptomatic humans and 92% of ALA subjects(P>0.05).

  17. The novel C24D synthetic polypeptide inhibits binding of placenta immunosuppressive ferritin to human T cells and elicits anti-breast cancer immunity in vitro and in vivo.

    PubMed

    Solodeev, Inna; Zahalka, Muayad A; Moroz, Chaya

    2014-09-01

    Immune tolerance mechanisms supporting normal human pregnancy are exploited by breast cancer and other malignancies. We cloned from human placenta and breast cancer cells the novel human immunomodulator named placenta immunosuppressive ferritin (PLIF). PLIF is composed of a ferritin heavy chain-like domain and a novel cytokine-like domain, named C48. Both intact PLIF and C48 inhibit T cell proliferation. Blocking PLIF by specific antibodies in a tolerant breast cancer model in nude mice resulted in tumor cell apoptosis and rejection. This prompted us to study active immune preventive strategies targeting PLIF activity. Currently, we report on the design and synthesis of the novel C24D polypeptide, which inhibits the binding of PLIF to T cells and therefore inhibits the immune suppressive effect of PLIF. The effect of C24D on the generation of anti-breast cancer cytotoxic T lymphocytes (CTLs) was studied in vitro in cultures of MCF-7 (HLA-A2(+)) or T47D (HLA-A2(-)) breast cancer cells incubated with peripheral blood mononuclear cells (PBMCs) from healthy blood donors. We found that C24D treatment exclusively induced development of CTLs. On reactivation by their specific target cells, the CTLs secreted interferon-γ and induced target apoptosis. Anti-MCF-7 CTLs were cross-cytotoxic to MDA-MB-231 (HLA-A2(+)) triple-negative breast cancer but not to T47D. Moreover, C24D treatment in vivo inhibited the growth of MCF-7 tumors engrafted in immune-compromised nude mice transfused with naïve allogeneic human PBMCs. Our results demonstrate that C24D treatment breakdown breast cancer induced tolerance enabling the initiation of effective anti-tumor immune response.

  18. Mesenchymal Stem Cells Derived from Human Exocrine Pancreas Spontaneously Express Pancreas Progenitor-Cell Markers in a Cell-Passage-Dependent Manner

    PubMed Central

    Lee, Song; Lee, Chanmi; Oh, Jooyun

    2016-01-01

    Mesenchymal stem cells (MSCs) derived from bone marrow, adipose tissue, and most connective tissues have been recognized as promising sources for cell-based therapies. MSCs have also been detected in human pancreatic tissue, including endocrine and exocrine cells. These adult human pancreas-derived MSCs have generated a great deal of interest owing to their potential use in the differentiation of insulin-producing cells for diabetes treatment. In the present study, we isolated MSCs from the adult human exocrine pancreas to determine whether isolated MSCs have the potential to differentiate into pancreatic endocrine cells and, therefore, whether they can be used in stem cell-based therapies. Pancreatic tissue was digested by collagenase and an enriched exocrine-cell fraction was obtained by density-gradient separation. Crude exocrine cells were methodically cultured in suspension and then in adherent culture. We expanded the human pancreatic exocrine-derived MSCs (hpMSCs) by cell passaging in culture and confirmed by flow cytometry that >90% expressed human classic surface markers of MSCs. Interestingly, these cells expressed pancreatic transcription factors, such as Pdx1, Ngn3, and MafA, similar to pancreatic progenitor cells. These results indicated that hpMSCs can be used for the differentiation of pancreatic endocrine cells and may be used in type 1 diabetes treatment.

  19. Mesenchymal Stem Cells Derived from Human Exocrine Pancreas Spontaneously Express Pancreas Progenitor-Cell Markers in a Cell-Passage-Dependent Manner.

    PubMed

    Lee, Song; Jeong, Seonghee; Lee, Chanmi; Oh, Jooyun; Kim, Song-Cheol

    2016-01-01

    Mesenchymal stem cells (MSCs) derived from bone marrow, adipose tissue, and most connective tissues have been recognized as promising sources for cell-based therapies. MSCs have also been detected in human pancreatic tissue, including endocrine and exocrine cells. These adult human pancreas-derived MSCs have generated a great deal of interest owing to their potential use in the differentiation of insulin-producing cells for diabetes treatment. In the present study, we isolated MSCs from the adult human exocrine pancreas to determine whether isolated MSCs have the potential to differentiate into pancreatic endocrine cells and, therefore, whether they can be used in stem cell-based therapies. Pancreatic tissue was digested by collagenase and an enriched exocrine-cell fraction was obtained by density-gradient separation. Crude exocrine cells were methodically cultured in suspension and then in adherent culture. We expanded the human pancreatic exocrine-derived MSCs (hpMSCs) by cell passaging in culture and confirmed by flow cytometry that >90% expressed human classic surface markers of MSCs. Interestingly, these cells expressed pancreatic transcription factors, such as Pdx1, Ngn3, and MafA, similar to pancreatic progenitor cells. These results indicated that hpMSCs can be used for the differentiation of pancreatic endocrine cells and may be used in type 1 diabetes treatment. PMID:27630717

  20. Mesenchymal Stem Cells Derived from Human Exocrine Pancreas Spontaneously Express Pancreas Progenitor-Cell Markers in a Cell-Passage-Dependent Manner

    PubMed Central

    Lee, Song; Lee, Chanmi; Oh, Jooyun

    2016-01-01

    Mesenchymal stem cells (MSCs) derived from bone marrow, adipose tissue, and most connective tissues have been recognized as promising sources for cell-based therapies. MSCs have also been detected in human pancreatic tissue, including endocrine and exocrine cells. These adult human pancreas-derived MSCs have generated a great deal of interest owing to their potential use in the differentiation of insulin-producing cells for diabetes treatment. In the present study, we isolated MSCs from the adult human exocrine pancreas to determine whether isolated MSCs have the potential to differentiate into pancreatic endocrine cells and, therefore, whether they can be used in stem cell-based therapies. Pancreatic tissue was digested by collagenase and an enriched exocrine-cell fraction was obtained by density-gradient separation. Crude exocrine cells were methodically cultured in suspension and then in adherent culture. We expanded the human pancreatic exocrine-derived MSCs (hpMSCs) by cell passaging in culture and confirmed by flow cytometry that >90% expressed human classic surface markers of MSCs. Interestingly, these cells expressed pancreatic transcription factors, such as Pdx1, Ngn3, and MafA, similar to pancreatic progenitor cells. These results indicated that hpMSCs can be used for the differentiation of pancreatic endocrine cells and may be used in type 1 diabetes treatment. PMID:27630717

  1. The Elicitation of Vocal Responses from Preschool Children.

    ERIC Educational Resources Information Center

    Champley, Elizabeth Hyne; Andrews, Moya L.

    1993-01-01

    This article discusses the construction of tasks used to elicit vocal responses from preschool children with and without communication disorders. Procedures to elicit valid and reliable responses are proposed, and a sample assessment protocol is presented. (Author/DB)

  2. Organohalogenated contaminants in domestic cats' plasma in relation to spontaneous acromegaly and type 2 diabetes mellitus: a clue for endocrine disruption in humans?

    PubMed

    Dirtu, Alin C; Niessen, Stijn J M; Jorens, Philippe G; Covaci, Adrian

    2013-07-01

    It was recently hypothesized that pets may serve as sentinels to explore human exposure to organohalogenated chemicals (OHCs) via indoor environments and adverse health effects. The current study investigates OHCs contamination in domestic cats suffering from diabetes mellitus (DM), particularly DM induced by acromegaly and a form of DM akin to human type 2 DM (T2DM). Plasma from three groups of domestic cats was analyzed: acromegaly induced DM, T2DM and age matched control cats without DM. Analytes targeted included organochlorine pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs), together with their hydroxylated (HO-) metabolites. Similar PCB profiles were measured in cat plasma compared to humans, while the PBDE profile (dominated by BDE-99 (48%-55%) and BDE-47 (19%-25%)), the PCB and PBDE metabolite profiles were different in cat plasma than found in humans. Significantly higher OHC concentrations were recorded in plasma of acromegalic cats compared to the other two groups. Group differences in the PCBs/HO-PCBs ratios suggest that acromegalic cats have a lower capacity to metabolize persistent OHCs, like PCBs, than diabetic cats or cats without an endocrinopathy. As pituitary tumorigenesis in animals can be induced by estrogens, and PCBs may act as xenoestrogens, further investigation into whether there could be a causative link with the induction of feline acromegaly is warranted. Interestingly, BDE-47/BDE-99 ratios in cats were similar to the ratios in house dust. The results of this study suggest that domestic cats may represent a good model to assess human exposure to chemicals present in indoor dust.

  3. Spontaneous acalculous gallbladder perforation

    PubMed Central

    Sheridan, David; Qazi, Almas; Lisa, Selina; Vashisht, Rajiv

    2014-01-01

    An 86-year-old woman, 4 days post-operative following a right-sided Austin-Moore arthroplasty, reported abdominal pain around a known umbilical hernia and became increasingly confused. A diagnosis of incarcerated umbilical hernia was made. At surgery, on entering the peritoneal cavity, bile was immediately noted. The operation was converted to a laparotomy and a perforation was noted in the gallbladder. An open cholecystectomy was performed. Macroscopically the gallbladder was perforated in multiple places, was thin walled and did not contain gallstones. This case demonstrates the difficulty in diagnosing an apparently spontaneous gallbladder perforation in a cognitively frail patient. PMID:25293685

  4. Spontaneous Symmetry Breaking

    NASA Astrophysics Data System (ADS)

    Strocchi, Franco

    One of the most powerful ideas of modern theoretical physics is the mechanism of spontaneous symmetry breaking. It is at the basis of most of the recent achievements in the description of phase transitions in Statistical Mechanics as well as of collective phenomena in solid state physics. It has also made possible the unification of weak, electromagnetic and strong interactions in elementary particle physics. Philosophically, the idea is very deep and subtle (this is probably why its exploitation is a rather recent achievement) and the popular accounts do not fully do justice to it.

  5. Spontaneous acalculous gallbladder perforation.

    PubMed

    Sheridan, David; Qazi, Almas; Lisa, Selina; Vashisht, Rajiv

    2014-10-07

    An 86-year-old woman, 4 days post-operative following a right-sided Austin-Moore arthroplasty, reported abdominal pain around a known umbilical hernia and became increasingly confused. A diagnosis of incarcerated umbilical hernia was made. At surgery, on entering the peritoneal cavity, bile was immediately noted. The operation was converted to a laparotomy and a perforation was noted in the gallbladder. An open cholecystectomy was performed. Macroscopically the gallbladder was perforated in multiple places, was thin walled and did not contain gallstones. This case demonstrates the difficulty in diagnosing an apparently spontaneous gallbladder perforation in a cognitively frail patient.

  6. Eliciting promises from children reduces cheating.

    PubMed

    Heyman, Gail D; Fu, Genyue; Lin, Jianyan; Qian, Miao K; Lee, Kang

    2015-11-01

    Widespread cheating can undermine rules that are necessary for maintaining social order. Preventing cheating can be a challenge, especially with regard to children, who as a result of their limited executive function skills may have particular difficulty with resisting temptation to cheat. We examined one approach designed to help children resist this temptation: eliciting a verbal commitment to not cheat. We tested 4- to 7-year-olds (total N = 330) and found that starting at 5 years of age, a verbal commitment to not cheat led to a substantial reduction in cheating. The results suggest that verbal commitments can be used to help children overcome temptations and comply with rules.

  7. [Spontaneous course of depression].

    PubMed

    Azorin, J M

    1995-03-01

    The study of the spontaneous course of depressions nowadays comes up against a number of obstacles. The most important of these is the necessity of using untreated cases, which virtually forces the contemporary researcher to refer to studies performed in the pretherapeutic era, if conclusions are not be drawn only from classical descriptions. Unfortunately, these studies are marked by the absence of strict diagnostic criteria, the heterogeneity of patients included in them, the lack of preciseness of evaluations and the primitive statistical methods used. They are concerned essentially with the duration of depressive phases and the factors which influence it. Among these latter are regularly found age, sex, the number of episodes, the duration of the preceding symptom-free interval, the severity and semiology of the attack, heredity, mode of onset, level of intelligence, the presence or absence of associated pathology and the presence or absence of hospitalisation. Chronicization of depression and the factors concerned with it have also been the object of several studies. A small number of investigations compare the course of the illness in untreated populations. The study of the spontaneous course of depression evidences the necessity of having consensus definitions, and may serve as a basis for a better comprehension of the process of cure and of the real impact of therapies designed to treat depression.

  8. Vaccination with 2014-15 Seasonal Inactivated Influenza Vaccine Elicits Cross-Reactive Anti-HA Antibodies with Strong ADCC Against Antigenically Drifted Circulating H3N2 Virus in Humans.

    PubMed

    Zhong, Weimin; Gross, F Liaini; Holiday, Crystal; Jefferson, Stacie N; Bai, Yaohui; Liu, Feng; Katz, Jacqueline M; Levine, Min Z

    2016-05-01

    It is well established that virus neutralizing (VN) antibodies to hemagglutinin (HA) antigens of influenza A viruses provide optimal protection against antigenically matched strains of influenza A viruses. In contrast, little is known about the potential role of HA-specific, non-neutralizing antibodies in protection against human influenza illness at present. In this study, we show that individuals vaccinated with the 2014-15 seasonal inactivated influenza vaccine displayed strong A/H3N2 HA-specific antibody-dependent cell-mediated cytotoxicity (ADCC) activities against an antigenically drifted H3N2 virus, despite poor induction of cross-reactive neutralizing antibodies against the antigenic variant. Given that passive transfer of influenza HA-monospecific immune sera with negligible levels of HA-specific VN antibodies can often confer considerable cross protection against lethal challenge with heterologous influenza viruses in animal models, it is conceivable that HA-specific, non-neutralizing antibodies may provide certain degree of cross protection against antigenically drifted influenza A viruses through ADCC in case of influenza vaccine mismatches. This may have important implications for public health. PMID:26950058

  9. Spontaneous Metacognition in Rhesus Monkeys.

    PubMed

    Rosati, Alexandra G; Santos, Laurie R

    2016-09-01

    Metacognition is the ability to think about thinking. Although monitoring and controlling one's knowledge is a key feature of human cognition, its evolutionary origins are debated. In the current study, we examined whether rhesus monkeys (Macaca mulatta; N = 120) could make metacognitive inferences in a one-shot decision. Each monkey experienced one of four conditions, observing a human appearing to hide a food reward in an apparatus consisting of either one or two tubes. The monkeys tended to search the correct location when they observed this baiting event, but engaged in information seeking-by peering into a center location where they could check both potential hiding spots-if their view had been occluded and information seeking was possible. The monkeys only occasionally approached the center when information seeking was not possible. These results show that monkeys spontaneously use information about their own knowledge states to solve naturalistic foraging problems, and thus provide the first evidence that nonhumans exhibit information-seeking responses in situations with which they have no prior experience. PMID:27388917

  10. Spontaneous Metacognition in Rhesus Monkeys.

    PubMed

    Rosati, Alexandra G; Santos, Laurie R

    2016-09-01

    Metacognition is the ability to think about thinking. Although monitoring and controlling one's knowledge is a key feature of human cognition, its evolutionary origins are debated. In the current study, we examined whether rhesus monkeys (Macaca mulatta; N = 120) could make metacognitive inferences in a one-shot decision. Each monkey experienced one of four conditions, observing a human appearing to hide a food reward in an apparatus consisting of either one or two tubes. The monkeys tended to search the correct location when they observed this baiting event, but engaged in information seeking-by peering into a center location where they could check both potential hiding spots-if their view had been occluded and information seeking was possible. The monkeys only occasionally approached the center when information seeking was not possible. These results show that monkeys spontaneously use information about their own knowledge states to solve naturalistic foraging problems, and thus provide the first evidence that nonhumans exhibit information-seeking responses in situations with which they have no prior experience.

  11. Isolated sleep paralysis elicited by sleep interruption.

    PubMed

    Takeuchi, T; Miyasita, A; Sasaki, Y; Inugami, M; Fukuda, K

    1992-06-01

    We elicited isolated sleep paralysis (ISP) from normal subjects by a nocturnal sleep interruption schedule. On four experimental nights, 16 subjects had their sleep interrupted for 60 minutes by forced awakening at the time when 40 minutes of nonrapid eye movement (NREM) sleep had elapsed from the termination of rapid eye movement (REM) sleep in the first or third sleep cycle. This schedule produced a sleep onset REM period (SOREMP) after the interruption at a high rate of 71.9%. We succeeded in eliciting six episodes of ISP in the sleep interruptions performed (9.4%). All episodes of ISP except one occurred from SOREMP, indicating a close correlation between ISP and SOREMP. We recorded verbal reports about ISP experiences and recorded the polysomnogram (PSG) during ISP. All of the subjects with ISP experienced inability to move and were simultaneously aware of lying in the laboratory. All but one reported auditory/visual hallucinations and unpleasant emotions. PSG recordings during ISP were characterized by a REM/W stage dissociated state, i.e. abundant alpha electroencephalographs and persistence of muscle atonia shown by the tonic electromyogram. Judging from the PSG recordings, ISP differs from other dissociated states such as lucid dreaming, nocturnal panic attacks and REM sleep behavior disorders. We compare some of the sleep variables between ISP and non-ISP nights. We also discuss the similarities and differences between ISP and sleep paralysis in narcolepsy. PMID:1621022

  12. Isolated sleep paralysis elicited by sleep interruption.

    PubMed

    Takeuchi, T; Miyasita, A; Sasaki, Y; Inugami, M; Fukuda, K

    1992-06-01

    We elicited isolated sleep paralysis (ISP) from normal subjects by a nocturnal sleep interruption schedule. On four experimental nights, 16 subjects had their sleep interrupted for 60 minutes by forced awakening at the time when 40 minutes of nonrapid eye movement (NREM) sleep had elapsed from the termination of rapid eye movement (REM) sleep in the first or third sleep cycle. This schedule produced a sleep onset REM period (SOREMP) after the interruption at a high rate of 71.9%. We succeeded in eliciting six episodes of ISP in the sleep interruptions performed (9.4%). All episodes of ISP except one occurred from SOREMP, indicating a close correlation between ISP and SOREMP. We recorded verbal reports about ISP experiences and recorded the polysomnogram (PSG) during ISP. All of the subjects with ISP experienced inability to move and were simultaneously aware of lying in the laboratory. All but one reported auditory/visual hallucinations and unpleasant emotions. PSG recordings during ISP were characterized by a REM/W stage dissociated state, i.e. abundant alpha electroencephalographs and persistence of muscle atonia shown by the tonic electromyogram. Judging from the PSG recordings, ISP differs from other dissociated states such as lucid dreaming, nocturnal panic attacks and REM sleep behavior disorders. We compare some of the sleep variables between ISP and non-ISP nights. We also discuss the similarities and differences between ISP and sleep paralysis in narcolepsy.

  13. Expression of Interferon γ by Decidual Cells and Natural Killer Cells at the Human Implantation Site: Implications for Preeclampsia, Spontaneous Abortion, and Intrauterine Growth Restriction.

    PubMed

    Chen, Chie-Pein; Piao, Longzhu; Chen, Xilin; Yu, Jianhua; Masch, Rachel; Schatz, Frederick; Lockwood, Charles J; Huang, S Joseph

    2015-11-01

    Human first-trimester decidual cells (FTDCs) chemoattract CXCR3-expressing circulating CD56(bright)CD16(-) natural killer (NK) cells, which increase uteroplacental blood flow by remodeling spiral arteries and arterioles. This recruitment reflects elevated FTDC expression of NK cell-recruiting induced protein 10 and interferon (IFN)-inducible T-cell-α chemoattractant produced in response to the synergistic effects of tumor necrosis factor α (TNF-α) and IFN-γ stimulation. Decidual macrophages express TNF-α, whereas the cellular origin of IFN-γ is unclear. Therefore, this study aims to identify the cell source(s) of IFN-γ in human first trimester decidua. Immunostaining of decidual sections revealed that both FTDCs and decidual NK (dNK) cells express IFN-γ. Although individual dNK cells express higher IFN-γ levels, the more numerous FTDCs account for greater proportion of total IFN-γ immunostaining. Freshly isolated FTDCs express greater IFN-γ staining than dNK cells as measured by flow cytometry, whereas incubation of dNK cells with documented NK cell activators significantly increases IFN-γ above FTDC levels. Confluent FTDCs intrinsically produce, but paradoxically respond to, exogenous IFN-γ.

  14. Structure of the network mediating siphon-elicited siphon withdrawal in Aplysia.

    PubMed

    Frost, W N; Kandel, E R

    1995-06-01

    1. The network mediating siphon-elicited siphon withdrawal in Aplysia is a useful model system for cellular studies of simple forms of learning and memory. Here we describe three new cells in this circuit, L33, L34, and L35, and several new connections among the following network neurons: LE, L16, L29, L30, L32, L33, L34, and L35. On the basis of these findings we present an updated diagram of the network. Altogether, 100 neurons have now been identified in the abdominal ganglion that can participate in both siphon-elicited and spontaneous respiratory pumping siphon withdrawals. 2. Two features of the interneuronal population may have important behavioral functions. First, the L29 interneurons make fast and slow excitatory connections onto the LFS cells, which may be important for transforming brief sensory neuron discharges into the long-lasting motor neuron firing that underlies withdrawal duration. Second, inhibitory interneurons are prominent in the network. The specific connectivity of certain of these interneurons is appropriate to block potentially interfering inhibitory inputs from other networks during execution of the behavior. 3. Deliberate searches have so far revealed very few excitatory interneuronal inputs to the network interneurons and motor neurons within the abdominal ganglion. These results, together with intracellular studies by others, are more consistent at present with a relatively dedicated rather than a highly distributed organizational scheme for the siphon-elicited siphon withdrawal circuitry.

  15. Elicitation: a tool for enriching the bioactive composition of foods.

    PubMed

    Baenas, Nieves; García-Viguera, Cristina; Moreno, Diego A

    2014-01-01

    Elicitation is a good strategy to induce physiological changes and stimulate defense or stress-induced responses in plants. The elicitor treatments trigger the synthesis of phytochemical compounds in fruits, vegetables and herbs. These metabolites have been widely investigated as bioactive compounds responsible of plant cell adaptation to the environment, specific organoleptic properties of foods, and protective effects in human cells against oxidative processes in the development of neurodegenerative and cardiovascular diseases and certain types of cancer. Biotic (biological origin), abiotic (chemical or physical origin) elicitors and phytohormones have been applied alone or in combinations, in hydroponic solutions or sprays, and in different selected time points of the plant growth or during post-harvest. Understanding how plant tissues and their specific secondary metabolic pathways respond to specific treatments with elicitors would be the basis for designing protocols to enhance the production of secondary metabolites, in order to produce quality and healthy fresh foods. PMID:25255755

  16. 8-Month-Old Infants Spontaneously Learn and Generalize Hierarchical Rules

    PubMed Central

    Werchan, Denise M.; Collins, Anne G. E.; Frank, Michael J.; Amso, Dima

    2015-01-01

    The ability to extract hierarchically organized rule structures from noisy environments is critical to human cognitive, social, and emotional intelligence. Adults spontaneously create hierarchical rule structures of this sort. In the present research, we conducted two experiments to examine the previously unknown developmental origins of this hallmark skill. In Experiment 1, we exploited a visual paradigm previously shown to elicit incidental hierarchical rule learning in adults. In Experiment 2, we used the same learning structure to examine whether these hierarchical-rule-learning mechanisms are domain general and can help infants learn spoken object-label mappings across different speaker contexts. In both experiments, we found that 8-month-olds created and generalized hierarchical rules during learning. Eyeblink rate, an exploratory indicator of striatal dopamine activity, mirrored behavioral-learning patterns. Our results provide direct evidence that the human brain is predisposed to extract knowledge from noisy environments, and they add a fundamental learning mechanism to what is currently known about the neurocognitive toolbox available to infants. PMID:25878172

  17. Effects of post-extinction l-DOPA administration on the spontaneous recovery and reinstatement of fear in a human fMRI study.

    PubMed

    Haaker, Jan; Lonsdorf, Tina B; Kalisch, Raffael

    2015-10-01

    Relapse is a pertinent problem in the treatment of anxiety disorders. In the laboratory, relapse is modeled as return of conditioned fear responses after successful fear extinction and is explained by insufficient retrieval and/or expression of the fear-inhibitory extinction memory that is generated during extinction learning. We have shown in mice and humans that return of fear can be prevented by administration of a single dose of the dopamine precursor l-3,4-dihydroxyphenylalanine (l-DOPA) immediately after extinction. In mice, this effect could be attributed to an enhancement of extinction memory consolidation. In our human study, we could not exclude that l-DOPA might have acted by interfering with the consolidation of the original fear memory. In the present study, we therefore used a combined differential cue and context conditioning paradigm where initial fear conditioning and extinction were conducted one day apart, in analogy to previous mouse studies. l-DOPA (N=21) or placebo (N=19) were administered after extinction, precluding any action on fear memory consolidation. In the return-of-fear test conducted one week later, drug effects on conditioned skin conductance responses were absent. However, we found evidence indicative of reduced neural activity, measured with functional magnetic resonance imaging (fMRI), in the l-DOPA group in areas related to conditioned fear and return of fear (amygdala, posterior hippocampus) and enhanced activity in a key area of extinction retrieval/expression (ventromedial prefrontal cortex), relative to placebo controls. These findings require further corroboration in additional experiments. Implications for further investigations on the role of the dopamine system in extinction and on the neuropharmacological augmentation of extinction-based therapies are discussed. PMID:26238968

  18. Effects of post-extinction l-DOPA administration on the spontaneous recovery and reinstatement of fear in a human fMRI study.

    PubMed

    Haaker, Jan; Lonsdorf, Tina B; Kalisch, Raffael

    2015-10-01

    Relapse is a pertinent problem in the treatment of anxiety disorders. In the laboratory, relapse is modeled as return of conditioned fear responses after successful fear extinction and is explained by insufficient retrieval and/or expression of the fear-inhibitory extinction memory that is generated during extinction learning. We have shown in mice and humans that return of fear can be prevented by administration of a single dose of the dopamine precursor l-3,4-dihydroxyphenylalanine (l-DOPA) immediately after extinction. In mice, this effect could be attributed to an enhancement of extinction memory consolidation. In our human study, we could not exclude that l-DOPA might have acted by interfering with the consolidation of the original fear memory. In the present study, we therefore used a combined differential cue and context conditioning paradigm where initial fear conditioning and extinction were conducted one day apart, in analogy to previous mouse studies. l-DOPA (N=21) or placebo (N=19) were administered after extinction, precluding any action on fear memory consolidation. In the return-of-fear test conducted one week later, drug effects on conditioned skin conductance responses were absent. However, we found evidence indicative of reduced neural activity, measured with functional magnetic resonance imaging (fMRI), in the l-DOPA group in areas related to conditioned fear and return of fear (amygdala, posterior hippocampus) and enhanced activity in a key area of extinction retrieval/expression (ventromedial prefrontal cortex), relative to placebo controls. These findings require further corroboration in additional experiments. Implications for further investigations on the role of the dopamine system in extinction and on the neuropharmacological augmentation of extinction-based therapies are discussed.

  19. Spontaneous soft tissue hematomas.

    PubMed

    Dohan, A; Darnige, L; Sapoval, M; Pellerin, O

    2015-01-01

    Spontaneous muscle hematomas are a common and serious complication of anticoagulant treatment. The incidence of this event has increased along with the rise in the number of patients receiving anticoagulants. Radiological management is both diagnostic and interventional. Computed tomography angiography (CTA) is the main tool for the detection of hemorrhage to obtain a positive, topographic diagnosis and determine the severity. Detection of an active leak of contrast material during the arterial or venous phase is an indication for the use of arterial embolization. In addition, the interventional radiological procedure can be planned with CTA. Arterial embolization of the pedicles that are the source of the bleeding is an effective technique. The rate of technical and clinical success is 90% and 86%, respectively. PMID:26066549

  20. Spontaneous Iliac Vein Rupture

    PubMed Central

    Kim, Dae Hwan; Park, Hyung Sub; Lee, Taeseung

    2015-01-01

    Spontaneous iliac vein rupture (SIVR) is a rare entity, which usually occurs without a precipitating factor, but can be a life-threatening emergency often requiring an emergency operation. This is a case report of SIVR in a 62-year-old female who presented to the emergency room with left leg swelling. Workup with contrast-enhanced computed tomography revealed a left leg deep vein thrombosis with May-Thurner syndrome and a hematoma in the pelvic cavity without definite evidence of arterial bleeding. She was managed conservatively without surgical intervention, and also underwent inferior vena cava filter insertion and subsequent anticoagulation therapy for pulmonary thromboembolism. This case shows that SIVR can be successfully managed with close monitoring and conservative management, and anticoagulation may be safely applied despite the patient presenting with venous bleeding. PMID:26217647

  1. Spontaneous Coronary Artery Dissection.

    PubMed

    Tweet, Marysia S; Gulati, Rajiv; Hayes, Sharonne N

    2016-07-01

    Spontaneous coronary artery dissection is an important etiology of nonatherosclerotic acute coronary syndrome, myocardial infarction, and sudden death. Innovations in the catheterization laboratory including optical coherence tomography and intravascular ultrasound have enhanced the ability to visualize intimal disruption and intramural hematoma associated with SCAD. Formerly considered "rare," these technological advances and heightened awareness suggest that SCAD is more prevalent than prior estimates. SCAD is associated with female sex, young age, extreme emotional stress, or extreme exertion, pregnancy, and fibromuscular dysplasia. The clinical characteristics and management strategies of SCAD patients are different than for atherosclerotic heart disease and deserve specific consideration. This review will highlight recent discoveries about SCAD as well as describe current efforts to elucidate remaining gaps in knowledge.

  2. Spontaneous Coronary Artery Dissection.

    PubMed

    Tweet, Marysia S; Gulati, Rajiv; Hayes, Sharonne N

    2016-07-01

    Spontaneous coronary artery dissection is an important etiology of nonatherosclerotic acute coronary syndrome, myocardial infarction, and sudden death. Innovations in the catheterization laboratory including optical coherence tomography and intravascular ultrasound have enhanced the ability to visualize intimal disruption and intramural hematoma associated with SCAD. Formerly considered "rare," these technological advances and heightened awareness suggest that SCAD is more prevalent than prior estimates. SCAD is associated with female sex, young age, extreme emotional stress, or extreme exertion, pregnancy, and fibromuscular dysplasia. The clinical characteristics and management strategies of SCAD patients are different than for atherosclerotic heart disease and deserve specific consideration. This review will highlight recent discoveries about SCAD as well as describe current efforts to elucidate remaining gaps in knowledge. PMID:27216840

  3. Spontaneous and specific myogenic differentiation of human mesenchymal stem cells on polyethylene glycol-linked multi-walled carbon nanotube films for skeletal muscle engineering.

    PubMed

    Zhao, Chunyan; Andersen, Henrik; Ozyilmaz, Barbaros; Ramaprabhu, Sundara; Pastorin, Giorgia; Ho, Han Kiat

    2015-11-21

    This study explored the influence of polyethylene glycol-linked multi-walled carbon nanotube (PEG-CNT) films on skeletal myogenic differentiation of human mesenchymal stem cells (hMSCs). PEG-CNT films were prepared with nanoscale surface roughness, orderly arrangement of PEG-CNTs, high hydrophilicity and high mechanical strength. Notably, PEG-CNT films alone could direct the skeletal myogenic differentiation of hMSCs in the absence of myogenic induction factors. The quantitative real-time polymerase chain reaction (RT-PCR) showed that the non-induced hMSCs plated on the PEG-CNT films, compared to the negative control, presented significant up-regulation of general myogenic markers including early commitment markers of myoblast differentiation protein-1 (MyoD) and desmin, as well as a late phase marker of myosin heavy chain-2 (MHC). Corresponding protein analysis by immunoblot assays corroborated these results. Skeletal muscle-specific markers, fast skeletal troponin-C (TnC) and ryanodine receptor-1 (Ryr) were also significantly increased in the non-induced hMSCs on PEG-CNT films by RT-PCR. For these cells, the commitment to specific skeletal myoblasts was further proved by the absence of enhanced adipogenic, chondrogenic and osteogenic markers. This study elucidated that PEG-CNT films supported a dedicated differentiation of hMSCs into a skeletal myogenic lineage and can work as a promising material towards skeletal muscle injury repair. PMID:26486984

  4. Rocking to the beat: effects of music and partner's movements on spontaneous interpersonal coordination.

    PubMed

    Demos, Alexander P; Chaffin, Roger; Begosh, Kristen T; Daniels, Jennifer R; Marsh, Kerry L

    2012-02-01

    People move to music and coordinate their movements with others spontaneously. Does music enhance spontaneous coordination? We compared the influence of visual information (seeing or not seeing another person) and auditory information (hearing movement or music or hearing no sound) on spontaneous coordination. Pairs of participants were seated side by side in rocking chairs, told a cover story, and asked to rock at a comfortable rate. Both seeing and hearing the other person rock elicited spontaneous coordination, and effects of hearing amplified those of seeing. Coupling with the music was weaker than with the partner, and the music competed with the partner's influence, reducing coordination. Music did, however, function as a kind of social glue: participants who synchronized more with the music felt more connected.

  5. Spontaneous and specific myogenic differentiation of human mesenchymal stem cells on polyethylene glycol-linked multi-walled carbon nanotube films for skeletal muscle engineering

    NASA Astrophysics Data System (ADS)

    Zhao, Chunyan; Andersen, Henrik; Ozyilmaz, Barbaros; Ramaprabhu, Sundara; Pastorin, Giorgia; Ho, Han Kiat

    2015-10-01

    This study explored the influence of polyethylene glycol-linked multi-walled carbon nanotube (PEG-CNT) films on skeletal myogenic differentiation of human mesenchymal stem cells (hMSCs). PEG-CNT films were prepared with nanoscale surface roughness, orderly arrangement of PEG-CNTs, high hydrophilicity and high mechanical strength. Notably, PEG-CNT films alone could direct the skeletal myogenic differentiation of hMSCs in the absence of myogenic induction factors. The quantitative real-time polymerase chain reaction (RT-PCR) showed that the non-induced hMSCs plated on the PEG-CNT films, compared to the negative control, presented significant up-regulation of general myogenic markers including early commitment markers of myoblast differentiation protein-1 (MyoD) and desmin, as well as a late phase marker of myosin heavy chain-2 (MHC). Corresponding protein analysis by immunoblot assays corroborated these results. Skeletal muscle-specific markers, fast skeletal troponin-C (TnC) and ryanodine receptor-1 (Ryr) were also significantly increased in the non-induced hMSCs on PEG-CNT films by RT-PCR. For these cells, the commitment to specific skeletal myoblasts was further proved by the absence of enhanced adipogenic, chondrogenic and osteogenic markers. This study elucidated that PEG-CNT films supported a dedicated differentiation of hMSCs into a skeletal myogenic lineage and can work as a promising material towards skeletal muscle injury repair.This study explored the influence of polyethylene glycol-linked multi-walled carbon nanotube (PEG-CNT) films on skeletal myogenic differentiation of human mesenchymal stem cells (hMSCs). PEG-CNT films were prepared with nanoscale surface roughness, orderly arrangement of PEG-CNTs, high hydrophilicity and high mechanical strength. Notably, PEG-CNT films alone could direct the skeletal myogenic differentiation of hMSCs in the absence of myogenic induction factors. The quantitative real-time polymerase chain reaction (RT-PCR) showed

  6. Spontaneous prosocial choice by chimpanzees

    PubMed Central

    Horner, Victoria; Carter, J. Devyn; Suchak, Malini; de Waal, Frans B. M.

    2011-01-01

    The study of human and primate altruism faces an evolutionary anomaly: There is ample evidence for altruistic preferences in our own species and growing evidence in monkeys, but one of our closest relatives, the chimpanzee (Pan troglodytes), is viewed as a reluctant altruist, acting only in response to pressure and solicitation. Although chimpanzee prosocial behavior has been reported both in observational captive studies and in the wild, thus far Prosocial Choice Tests have failed to produce evidence. However, methodologies of previous Prosocial Choice Tests may have handicapped the apes unintentionally. Here we present findings of a paradigm in which chimpanzees chose between two differently colored tokens: one “selfish” token resulting in a reward for the actor only (1/0), and the other “prosocial” token rewarding both the actor and a partner (1/1). Seven female chimpanzees, each tested with three different partners, showed a significant bias for the prosocial option. Prosocial choices occurred both in response to solicitation by the partner and spontaneously without solicitation. However, directed requests and pressure by the partner reduced the actor's prosocial tendency. These results draw into question previous conclusions indicating that chimpanzees have a limited sensitivity to the needs of others and behave prosocially only in response to significant prompting. PMID:21825175

  7. Caffeine in hot drinks elicits cephalic phase responses involving cardiac activity.

    PubMed

    McMullen, Michael K; Whitehouse, Julie M; Shine, Gillian; Whitton, Peter A; Towell, Anthony

    2012-09-01

    Caffeine stimulates both oropharyngeal and gut bitter taste receptors (hTAS2Rs) and so has the potential to elicit reflex autonomic responses. Coffee containing 130 mg caffeine has been reported to increase heart rate for 30 min post-ingestion. Whereas added-caffeine, in doses of 25 to 200 mg, ingested with decaffeinated coffee/tea decreases heart rate 10 to 30 min post-ingestion. This study aimed to clarify caffeine's chemosensory impact. Double-espresso coffees were compared to a placebo-control capsule in a double-blind between-measures design. Coffees tested were regular coffee (130 mg caffeine) and decaffeinated coffee with added-caffeine (0, 67 and 134 mg). Cardiovascular measures from three post-ingestion phases: 1) 0 to 5; 2) 10 to 15; and 3) 25 to 30 min; were compared to pre-ingestion measures. Participants comprised 11 women in the control group and 10 women in the test group. Decaffeinated coffee elicited no changes. Decaffeinated coffee with 67 mg caffeine: decreased dp/dt in Phase 1. Decaffeinated coffee with 134 mg caffeine: increased heart rate in Phases 1 and 2; decreased spontaneous baroreflex sensitivity in Phase 1; and increased diastolic pressure in Phases 2 and 3. Regular coffee: increased heart rate in Phases 1 and 2; decreased dp/dt in all phases; and decreased systolic pressure in Phase 1. Caffeine is the substance in regular coffee which elicits chemosensory autonomic reflex responses, which involves heart activity and the baroreflex. Compared to the caffeine in regular coffee, added-caffeine elicits somewhat different chemosensory responses including a more pronounced pressor effect and resetting of the baroreflex. Caffeine in commonly consumed amounts, as well as modulating body processes by blocking adenosine receptors, can elicit reflex autonomic responses during the ingestion of caffeinated drinks. It is plausible that caffeine stimulates hTAS2Rs, during the ingestion of coffee, eliciting cephalic phase responses. These cephalic phase

  8. Caffeine in hot drinks elicits cephalic phase responses involving cardiac activity.

    PubMed

    McMullen, Michael K; Whitehouse, Julie M; Shine, Gillian; Whitton, Peter A; Towell, Anthony

    2012-09-01

    Caffeine stimulates both oropharyngeal and gut bitter taste receptors (hTAS2Rs) and so has the potential to elicit reflex autonomic responses. Coffee containing 130 mg caffeine has been reported to increase heart rate for 30 min post-ingestion. Whereas added-caffeine, in doses of 25 to 200 mg, ingested with decaffeinated coffee/tea decreases heart rate 10 to 30 min post-ingestion. This study aimed to clarify caffeine's chemosensory impact. Double-espresso coffees were compared to a placebo-control capsule in a double-blind between-measures design. Coffees tested were regular coffee (130 mg caffeine) and decaffeinated coffee with added-caffeine (0, 67 and 134 mg). Cardiovascular measures from three post-ingestion phases: 1) 0 to 5; 2) 10 to 15; and 3) 25 to 30 min; were compared to pre-ingestion measures. Participants comprised 11 women in the control group and 10 women in the test group. Decaffeinated coffee elicited no changes. Decaffeinated coffee with 67 mg caffeine: decreased dp/dt in Phase 1. Decaffeinated coffee with 134 mg caffeine: increased heart rate in Phases 1 and 2; decreased spontaneous baroreflex sensitivity in Phase 1; and increased diastolic pressure in Phases 2 and 3. Regular coffee: increased heart rate in Phases 1 and 2; decreased dp/dt in all phases; and decreased systolic pressure in Phase 1. Caffeine is the substance in regular coffee which elicits chemosensory autonomic reflex responses, which involves heart activity and the baroreflex. Compared to the caffeine in regular coffee, added-caffeine elicits somewhat different chemosensory responses including a more pronounced pressor effect and resetting of the baroreflex. Caffeine in commonly consumed amounts, as well as modulating body processes by blocking adenosine receptors, can elicit reflex autonomic responses during the ingestion of caffeinated drinks. It is plausible that caffeine stimulates hTAS2Rs, during the ingestion of coffee, eliciting cephalic phase responses. These cephalic phase

  9. Hemodynamic responses to amygdaloid stimulation in spontaneously hypertensive rats.

    PubMed

    Galeno, T M; Brody, M J

    1983-08-01

    Our studies were done to determine 1) the regional hemodynamic effects of stimulating the central amygdaloid nucleus in conscious and anesthetized rats and 2) whether these effects differ between normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Flow was recorded with miniaturized pulsed Doppler probes placed on the renal and superior mesenteric arteries and the lower abdominal aorta. In rats anesthetized with Dialurethane, electrical stimulation elicited a depressor response accompanied by a decrease in hindquarter vascular resistance, with little or no change in heart rate or renal or mesenteric resistance in both SHR and WKY. By contrast, in conscious rats, stimulation was accompanied by a pressor response, tachycardia, and renal and mesenteric vasoconstriction in both groups. Hindquarter vascular resistance was unchanged in WKY and decreased at higher frequencies in SHR. There were no significant differences between SHR and WKY, whether anesthetized or awake, in hemodynamic responses to amygdaloid stimulation. Despite previous evidence indicating that the central amygdaloid nucleus contributes to the development of spontaneous hypertension, our results show that stimulation of this region does not elicit exaggerated cardiovascular responses in SHR.

  10. Spontaneous subgaleal aerocele.

    PubMed

    Ibe, M O N; Onu, D O; Igwe, N N

    2014-01-01

    Apart from reporting about a case of spontaneous subgaleal aerocele this paper looks at the possible causes and management also. A 35-year-old Igbo-Nigerian female, about 4 weeks post-natal, with a 10-month old steadily and gradually enlarging mass around the back of her head, including both temporal regions was referred to us. Plain skull radiographs showed air in this mass. Needle puncture produced air leading to immediate and complete flattening of the lesion. A few hours after this procedure while still in the hospital premises, she had generalized convulsions, for which she was hospitalized and treated. With no further attacks, her request for discharge the following day was granted. At the next visit, 7 days later, there was a re-accumulation, which was treated the same way as previously and with the same result. She has not reported back since then, though she was advised to visit us again in 7 day-time. This lesion should be considered when masses on the head are presented. Our health institutions should have adequate investigative facilities.

  11. Spontaneous breaking of supersymmetry

    SciTech Connect

    Zumino, B.

    1981-12-01

    There has been recently a revival of interest in supersymmetric gauge theories, stimulated by the hope that supersymmetry might help in clarifying some of the questions which remain unanswered in the so called Grand Unified Theories and in particular the gauge hierarchy problem. In a Grand Unified Theory one has two widely different mass scales: the unification mass M approx. = 10/sup 15/GeV at which the unification group (e.g. SU(5)) breaks down to SU(3) x SU(2) x U(1) and the mass ..mu.. approx. = 100 GeV at which SU(2) x U(1) is broken down to the U(1) of electromagnetism. There is at present no theoretical understanding of the extreme smallness of the ratio ..mu../M of these two numbers. This is the gauge hierarchy problem. This lecture attempts to review the various mechanisms for spontaneous supersymmetry breaking in gauge theories. Most of the discussions are concerned with the tree approximation, but what is presently known about radiative correction is also reviewed.

  12. High mutagenic activity of juice from pak choi (Brassica rapa ssp. chinensis) sprouts due to its content of 1-methoxy-3-indolylmethyl glucosinolate, and its enhancement by elicitation with methyl jasmonate.

    PubMed

    Wiesner, Melanie; Schreiner, Monika; Glatt, Hansruedi

    2014-05-01

    Cruciferous vegetables have the reputation to protect against cancer, an effect attributed to glucosinolates (GLS) and their breakdown products. However, some GLS are mutagenic, an activity associated with cancer initiation rather than chemoprevention. We show that juices from steamed pak choi sprouts are strongly mutagenic in Salmonella typhimurium TA100 upon addition of fresh myrosinase. Growth of the plants in the presence of methyl jasmonate, a hormone eliciting defence factors, led to 20-fold enhanced mutagenic activity. The level of 1-methoxy-3-indolylmethyl (1-MIM)-GLS was similarly increased, whereas those of other GLS were only elevated 0.8- to 3.2-fold. 1-MIM-GLS is a potent mutagen, whose activity is further enhanced by human sulphotransferase 1A1 (hSULT1A1), an activation not observed with other GLS. The mutagenicity of the pak choi juices was increased 20-fold in bacteria expressing hSULT1A1. A tiny level of juice from elicitated sprouts, 0.04% in the mutagenicity assay, was sufficient to double the number of revertants above the spontaneous level. We conclude that pak choi juice is mutagenic, an activity that can be strongly affected by the growth conditions. It is owed essentially to a single component, 1-MIM-GLS. We recommend using cultivars, growth conditions and/or food preparations that keep the level of this GLS congener low.

  13. Cripto-1 vaccination elicits protective immunity against metastatic melanoma.

    PubMed

    Ligtenberg, M A; Witt, K; Galvez-Cancino, F; Sette, A; Lundqvist, A; Lladser, A; Kiessling, R

    2016-05-01

    Metastatic melanoma is a fatal disease that responds poorly to classical treatments but can be targeted by T cell-based immunotherapy. Cancer vaccines have the potential to generate long-lasting cytotoxic CD8(+) T cell responses able to eradicate established and disseminated tumors. Vaccination against antigens expressed by tumor cells with enhanced metastatic potential represents a highly attractive strategy to efficiently target deadly metastatic disease. Cripto-1 is frequently over-expressed in human carcinomas and melanomas, but is expressed only at low levels on normal differentiated tissues. Cripto-1 is particularly upregulated in cancer-initiating cells and is involved in cellular processes such as cell migration, invasion and epithelial-mesenchymal transition, which are hallmarks of aggressive cancer cells able to initiate metastatic disease. Here, we explored the potential of Cripto-1 vaccination to target metastatic melanoma in a preclinical model. Cripto-1 was overexpressed in highly metastatic B16F10 cells as compared to poorly metastatic B16F1 cells. Moreover, B16F10 cells grown in sphere conditions to enrich for cancer stem cells (CSC) progressively upregulated cripto1 expression. Vaccination of C57Bl/6 mice with a DNA vaccine encoding mouse Cripto-1 elicited a readily detectable/strong cytotoxic CD8(+) T cell response specific for a H-2 Kb-restricted epitope identified based on its ability to bind H-2(b) molecules. Remarkably, Cripto-1 vaccination elicited a protective response against lung metastasis and subcutaneous challenges with highly metastatic B16F10 melanoma cells. Our data indicate that vaccination against Cripto-1 represents a novel strategy to be tested in the clinic. PMID:27467944

  14. Avian models with spontaneous autoimmune diseases

    PubMed Central

    Wick, Georg; Andersson, Leif; Hala, Karel; Gershwin, M. Eric; Selmi, Carlo F.; Erf, Gisela F.; Lamont, Susan J.; Sgonc, Roswitha

    2012-01-01

    Autoimmune diseases in human patients only become clinically manifest when the disease process has developed to a stage where functional compensation by the afflicted organ or system is not possible any more. In order to understand the initial etiologic and pathogenic events that are generally not yet accessible in humans, appropriate animal models are required. In this respect, spontaneously developing models - albeit rare – reflect the situation in humans much more closely than experimentally induced models, including knockout and transgenic mice. The present review describes three spontaneous chicken models for human autoimmune diseases, the Obese strain (OS) with a Hashimoto-like autoimmune thyroiditis, the University of California at Davis lines 200 and 206 (UCD-200 and 206) with a scleroderma-like disease and the amelanotic Smyth line with a vitiligo-like syndrome (SLV). Special emphasis is given to the new opportunities to unravel the genetic basis of these diseases in view of the recently completed sequencing of the chicken genome. PMID:17145302

  15. Spontaneous Neural Dynamics and Multi-scale Network Organization

    PubMed Central

    Foster, Brett L.; He, Biyu J.; Honey, Christopher J.; Jerbi, Karim; Maier, Alexander; Saalmann, Yuri B.

    2016-01-01

    Spontaneous neural activity has historically been viewed as task-irrelevant noise that should be controlled for via experimental design, and removed through data analysis. However, electrophysiology and functional MRI studies of spontaneous activity patterns, which have greatly increased in number over the past decade, have revealed a close correspondence between these intrinsic patterns and the structural network architecture of functional brain circuits. In particular, by analyzing the large-scale covariation of spontaneous hemodynamics, researchers are able to reliably identify functional networks in the human brain. Subsequent work has sought to identify the corresponding neural signatures via electrophysiological measurements, as this would elucidate the neural origin of spontaneous hemodynamics and would reveal the temporal dynamics of these processes across slower and faster timescales. Here we survey common approaches to quantifying spontaneous neural activity, reviewing their empirical success, and their correspondence with the findings of neuroimaging. We emphasize invasive electrophysiological measurements, which are amenable to amplitude- and phase-based analyses, and which can report variations in connectivity with high spatiotemporal precision. After summarizing key findings from the human brain, we survey work in animal models that display similar multi-scale properties. We highlight that, across many spatiotemporal scales, the covariance structure of spontaneous neural activity reflects structural properties of neural networks and dynamically tracks their functional repertoire. PMID:26903823

  16. Expert elicitation of population-level effects of disturbance

    USGS Publications Warehouse

    Fleishman, Erica; Burgman, Mark; Runge, Michael C.; Schick, Robert S; Krauss, Scott; Popper, Arthur N.; Hawkins, Anthony

    2016-01-01

    Expert elicitation is a rigorous method for synthesizing expert knowledge to inform decision making and is reliable and practical when field data are limited. We evaluated the feasibility of applying expert elicitation to estimate population-level effects of disturbance on marine mammals. Diverse experts estimated parameters related to mortality and sublethal injury of North Atlantic right whales (Eubalaena glacialis). We are now eliciting expert knowledge on the movement of right whales among geographic regions to parameterize a spatial model of health. Expert elicitation complements methods such as simulation models or extrapolations from other species, sometimes with greater accuracy and less uncertainty.

  17. Web-based tool for expert elicitation of the variogram

    NASA Astrophysics Data System (ADS)

    Truong, Phuong N.; Heuvelink, Gerard B. M.; Gosling, John Paul

    2013-02-01

    The variogram is the keystone of geostatistics. Estimation of the variogram is deficient and difficult when there are no or too few observations available due to budget constraints or physical and temporal obstacles. In such cases, expert knowledge can be an important source of information. Expert knowledge can also fulfil the increasing demand for an a priori variogram in Bayesian geostatistics and spatial sampling optimization. Formal expert elicitation provides a sound scientific basis to reliably and consistently extract knowledge from experts. In this study, we aimed at applying existing statistical expert elicitation techniques to extract the variogram of a regionalized variable that is assumed to have either a multivariate normal or lognormal spatial probability distribution from expert knowledge. To achieve this, we developed an elicitation protocol and implemented it as a web-based tool to facilitate the elicitation of beliefs from multiple experts. Our protocol has two main rounds: elicitation of the marginal probability distribution and elicitation of the variogram. The web-based tool has three main components: a web interface for expert elicitation and feedback; a component for statistical computation and mathematical pooling of multiple experts' knowledge; and a database management component. Results from a test case study show that the protocol is adequate and that the online elicitation tool functions satisfactorily. The web-based tool is free to use and supports scientists to conveniently elicit the variogram of spatial random variables from experts. The source code is available from the journal FTP site under the GNU General Public License.

  18. Expert Elicitation of Population-Level Effects of Disturbance.

    PubMed

    Fleishman, Erica; Burgman, Mark; Runge, Michael C; Schick, Robert S; Kraus, Scott

    2016-01-01

    Expert elicitation is a rigorous method for synthesizing expert knowledge to inform decision making and is reliable and practical when field data are limited. We evaluated the feasibility of applying expert elicitation to estimate population-level effects of disturbance on marine mammals. Diverse experts estimated parameters related to mortality and sublethal injury of North Atlantic right whales (Eubalaena glacialis). We are now eliciting expert knowledge on the movement of right whales among geographic regions to parameterize a spatial model of health. Expert elicitation complements methods such as simulation models or extrapolations from other species, sometimes with greater accuracy and less uncertainty. PMID:26610972

  19. Spontaneous contractions in elasmobranch vessels in vitro.

    PubMed

    Olson, K R; Forster, M E; Bushnell, P G; Duff, D W

    2000-05-01

    Isolated vessels from four elasmobranchs, yellow stingray (Urolophus jamaicensis), clearnose skate (Raja eglanteria), ghost shark (Hydrolagus novaezelandiae), and spiny dogfish (Squalus acanthias), were examined for the presence of spontaneous contractions (SC). SC were observed in otherwise unstimulated dorsal aortas (DA) from stingray and ghost shark, but not in skate DA. Unstimulated ventral aortas (VA) did not exhibit SC. After treatment of VA with a contractile agonist, SC appeared in stingray and skate but not ghost shark or dogfish. SC in stingray VA were subsequently inhibited by either epinephrine (10(-5) M) or indomethacin (10(-4) M). Agonist contraction also elicited strong SC in ductus Cuvier from stingray, but not from ghost shark or dogfish. SC in dogfish hepatic portal veins (HPV) produced a rhythmical oscillation in tension. The frequency of HPV SC was highest (approximately 1 min(-1)) in intact veins and lower (approximately 3 min(-1)) in vein segments, indicative of a dominant pacemaker in the intact vessel. SC in HPV were depressed during the first 30 min of hypoxia, but there was substantial recovery over an additional 30 min of hypoxia and complete recovery upon return to normoxia. Addition of 80 mM KCl completely inhibited HPV SC and lowered resting tone. These results show that SC are a common feature of elasmobranch vessels and there appears to be a correlation between swimming behavior and the propensity for SC. KCl inhibition of SC and tonus in HPV is highly unusual for vascular smooth muscle. PMID:10766969

  20. Spontaneous hypnosis in the forensic context.

    PubMed

    Beahrs, J O

    1989-01-01

    "Hypnosis" denotes either specific phenomena (altered volition, perception, cognition, and recall) or interpersonal transactions that often elicit them. Basic research leads to paradox: hypnosis is validated, and shown to be dissociative in essence, at the same time that neither its phenomena nor transactions can be separated from those of everyday living without logical absurdity. This paradox can be resolved by assuming that consciousness and volition are complex, occurring simultaneously at many levels in the same waking individual. Hypnotic-like phenomena and transactions occur spontaneously, in either covert or overt forms. The former are pervasive, whereas the latter are often associated with psychological trauma. Forensic implications are twofold: for criminal responsibility, and the reliability of eyewitness testimony. Hypnotic-like states and transactions are rarely affirmed as an insanity defense because at some level these subjects are aware of what they are doing and why. Diminished capacity and mitigation of sentence are more appropriate defense strategies. Several conflicted traditions of case law have evolved to protect eyewitness testimony from hypnotic-like distortions in cognition, perception, and memory that can occur either during or outside of formal hypnotic procedures. These include the admissibility of posthypnotic testimony, due process safeguards at eyewitness identification procedures, and the admissibility of expert testimony on the findings of eyewitness research. These areas are inseparable from one another and demand a systematic coordinated approach.

  1. Acting green elicits a literal warm glow

    NASA Astrophysics Data System (ADS)

    Taufik, Danny; Bolderdijk, Jan Willem; Steg, Linda

    2015-01-01

    Environmental policies are often based on the assumption that people only act environmentally friendly if some extrinsic reward is implicated, usually money. We argue that people might also be motivated by intrinsic rewards: doing the right thing (such as acting environmentally friendly) elicits psychological rewards in the form of positive feelings, a phenomenon known as warm glow. Given the fact that people's psychological state may affect their thermal state, we expected that this warm glow could express itself quite literally: people who act environmentally friendly may perceive the temperature to be higher. In two studies, we found that people who learned they acted environmentally friendly perceived a higher temperature than people who learned they acted environmentally unfriendly. The underlying psychological mechanism pertains to the self-concept: learning you acted environmentally friendly signals to yourself that you are a good person. Together, our studies show that acting environmentally friendly can be psychologically rewarding, suggesting that appealing to intrinsic rewards can be an alternative way to encourage pro-environmental actions.

  2. The spontaneous market order and evolution.

    PubMed

    Beck, Naomi

    2016-08-01

    Darwin's theory of natural selection and the idea of a spontaneous order share a fundamental feature: the claim that apparent design or order do not necessarily imply a designer or rational planning. But they also present important differences, which touch upon central questions such as the evolution of morality, the role of human agency in social evolution, the existence (or not) of directionality in undesigned processes, and the presence (nor not) of a providential element in evolutionary accounts. In this article, I explore these themes and probe the relationship between the notion of a spontaneous order and the theory of evolution by natural selection. The reflections of Nobel laureate in economics, F.A. von Hayek, provide the beginning and endpoint in this voyage, for they constitute the most pronounced effort to develop a full-fledged theory combining evolution and economics in recent times. But along the way, I also investigate the influence of classical political economy on Darwin's thought, primarily that of Adam Smith, and consider the reasons for which Darwin did not refer to Smith when discussing the principle of natural selection in The Origin of Species. I conclude that the spontaneous order, as understood by Hayek, and evolution by natural selection constitute two disparate concepts. PMID:26751793

  3. The spontaneous market order and evolution.

    PubMed

    Beck, Naomi

    2016-08-01

    Darwin's theory of natural selection and the idea of a spontaneous order share a fundamental feature: the claim that apparent design or order do not necessarily imply a designer or rational planning. But they also present important differences, which touch upon central questions such as the evolution of morality, the role of human agency in social evolution, the existence (or not) of directionality in undesigned processes, and the presence (nor not) of a providential element in evolutionary accounts. In this article, I explore these themes and probe the relationship between the notion of a spontaneous order and the theory of evolution by natural selection. The reflections of Nobel laureate in economics, F.A. von Hayek, provide the beginning and endpoint in this voyage, for they constitute the most pronounced effort to develop a full-fledged theory combining evolution and economics in recent times. But along the way, I also investigate the influence of classical political economy on Darwin's thought, primarily that of Adam Smith, and consider the reasons for which Darwin did not refer to Smith when discussing the principle of natural selection in The Origin of Species. I conclude that the spontaneous order, as understood by Hayek, and evolution by natural selection constitute two disparate concepts.

  4. Cell Motility Resulting form Spontaneous Polymerization Waves

    NASA Astrophysics Data System (ADS)

    Kruse, Karsten

    2014-03-01

    The crawling of living cells on solid substrates is often driven by the actin cytoskeleton, a network of structurally polar filamentous proteins that is intrinsically driven by the hydrolysis of ATP. How cells organize their actin network during crawling is still poorly understood. A possible general mechanism underlying actin organization has been offered by the observation of spontaneous actin polymerization waves in various different cell types. We use a theoretical approach to investigate the possible role of spontaneous actin waves on cell crawling. To this end, we develop a meanfield framework for studying spatiotemporal aspects of actin assembly dynamics, which helped to identify possible origins of self-organized actin waves. The impact of these waves on cell crawling is then investigated by using a phase-field approach to confine the actin network to a cellular domain. We find that spontaneous actin waves can lead to directional or amoeboidal crawling. In the latter case, the cell performs a random walk. Within our deterministic framework, this behavior is due to complex spiral waves inside the cell. Finally, we compare the seemingly random motion of our model cells to the dynamics of cells of the human immune system. These cells patrol the body in search for infected cells and we discuss possible implications of our theory for the search process' efficiency. Work was funded by the DFG through KR3430/1, GK1276, and SFB 1027.

  5. Spontaneous resolution of subfoveal perfluorocarbon

    PubMed Central

    Oellers, Patrick; Charkoudian, Leon D; Hahn, Paul

    2015-01-01

    Perfluorocarbon liquids (PFCL) have transformed the surgical approach to complex retinal detachments, but their use can be complicated by subretinal retention. Migration of peripherally located subretinal PFCL towards the fovea is well established, but spontaneous resolution of subfoveal PFCL without surgical evacuation or displacement has rarely been described. We present a case of a large single retained subfoveal PFCL droplet following vitrectomy with membrane peeling, inferior relaxing retinectomy, and silicone oil tamponade that demonstrated spontaneous resolution 3 weeks postoperatively, with subsequent anatomic and visual improvement. No residual subretinal PFCL was noted, and we hypothesize that the PFCL droplet spontaneously extruded through a transient hole created in the thinned retina overlying the droplet, which subsequently closed spontaneously. Further understanding of the mechanisms of PFCL migration and resolution may facilitate improved treatments for this complication. PMID:25834389

  6. Disturbances in the spontaneous attribution of social meaning in schizophrenia

    PubMed Central

    Horan, W. P.; Nuechterlein, K. H.; Wynn, J. K.; Lee, J.; Castelli, F.; Green, M. F.

    2010-01-01

    Background Schizophrenia patients show disturbances on a range of tasks that assess mentalizing or ‘Theory of Mind’ (ToM). However, these tasks are often developmentally inappropriate, make large demands on verbal abilities and explicit problem-solving skills, and involve after-the-fact reflection as opposed to spontaneous mentalizing. Method To address these limitations, 55 clinically stable schizophrenia out-patients and 44 healthy controls completed a validated Animations Task designed to assess spontaneous attributions of social meaning to ambiguous abstract visual stimuli. In this paradigm, 12 animations depict two geometric shapes ‘interacting’ with each other in three conditions : (1) ToM interactions that elicit attributions of mental states to the agents, (2) Goal-Directed (GD) interactions that elicit attributions of simple actions, and (3) Random scenes in which no interaction occurs. Verbal descriptions of each animation are rated for the degree of Intentionality attributed to the agents and for accuracy. Results Patients had lower Intentionality ratings than controls for ToM and GD scenes but the groups did not significantly differ for Random scenes. The descriptions of the patients less closely matched the situations intended by the developers of the task. Within the schizophrenia group, performance on the Animations Task showed minimal associations with clinical symptoms. Conclusions Patients demonstrated disturbances in the spontaneous attribution of mental states to abstract visual stimuli that normally evoke such attributions. Hence, in addition to previously established impairment on mentalizing tasks that require logical inferences about others’ mental states, individuals with schizophrenia show disturbances in implicit aspects of mentalizing. PMID:18606048

  7. Spontaneous Activity in Crustacean Neurons

    PubMed Central

    Preston, James B.; Kennedy, Donald

    1962-01-01

    Single units which discharged with regular spontaneous rhythms without intentional stimulation were observed in the ventral nerve cord by intracellular recording close to the sixth abdominal ganglion. These units were divided into two groups: group A units in which interspike intervals varied less than 10 msec.; group B units in which interspike intervals varied within a range of 10 to 30 msec. Group A units maintained "constant" interspike intervals and could not be discharged by sensory inputs, while the majority of group B units could be discharged by appropriate sensory nerve stimulation. Both group A and B units discharged to direct stimulation when the stimulating and recording electrodes were placed in the same ganglionic intersegment, and directly evoked single spikes reset the spontaneous rhythm. In group B units, presynaptic volleys reset the spontaneous rhythm of some units; but in others, synaptically evoked spikes were interpolated within the spontaneous rhythm without resetting. The phenomenon of enhancement could also be demonstrated in spontaneously active units as a result of repetitive stimulation. It is concluded that endogenous pacemaker activity is responsible for much of the regular spontaneous firing observed in crayfish central neurons, and that interaction of evoked responses with such pacemaker sites can produce a variety of effects dependent upon the anatomical relationships between pacemaker and synaptic regions. PMID:14488667

  8. The Chicken Model of Spontaneous Ovarian Cancer

    PubMed Central

    Hawkridge, Adam M.

    2014-01-01

    The chicken is a unique experimental model for studying the spontaneous onset and progression of ovarian cancer (OVC). The prevalence of OVC in chickens can range from 10–35% depending on age, genetic strain, reproductive history, and diet. Furthermore, the chicken presents epidemiological, morphological, and molecular traits that are similar to human OVC making it a relevant experimental model for translation research. Similarities to humans include associated increased risk of OVC with the number of ovulations, common histopathological sub-types including high-grade serous, and molecular-level markers or pathways such as CA-125 expression and p53 mutation frequency. Collectively, the similarities between chicken and human OVC combined with a tightly controlled genetic background and predictable onset window provides an outstanding experimental model for studying the early events and progression of spontaneous OVC tumors under controlled environmental conditions. This review will cover the existing literature on OVC in the chicken and highlight potential opportunities for further exploitation (e.g, biomarkers, prevention, treatment, and genomics). PMID:25130871

  9. [Spontaneous oscillations in basal blood insulin].

    PubMed

    Bellisle, F

    1987-02-01

    Many studies show that basal insulinemia is not stable over time, but oscillates significantly. The period and amplitude of oscillations appear species-specific. Studies on living animals have established that neither central autonomic command nor liver-pancreas feedback play a determining role on these cycles. Work on the isolated, perfused, canine pancreas has demonstrated the existence of an intrinsic pancreatic oscillator. Studies on human subjects confirm and complete animal data. The amplitude of insulinemia cycles is less in humans than in animals. In obese humans, insulin cycles are normal. In non-insulin-dependent diabetics, insulin oscillations are very irregular; after partial pancreatectomy (removal of the head of the pancreas), the normal insulin cycles disappear. The insulinemia cycles thus seem to reflect the behavior of an intrinsic pancreatic oscillator which synchronizes the activity of beta cells. Spontaneous oscillations in plasma insulin could play a role in the regulation of receptor affinity in target-tissues.

  10. Introducing Forum Theatre to Elicit and Advocate Children's Views

    ERIC Educational Resources Information Center

    Hammond, Nick

    2013-01-01

    Eliciting and advocating the voice of the child remains at the heart of international political agenda and also remains a central role for educational psychologists (EPs). Previous research indicates that EPs tend to use language-based methods for eliciting and advocating views of children. However, these approaches are often limited. Taking a…

  11. Science Teachers' Elicitation Practices: Insights for Formative Assessment

    ERIC Educational Resources Information Center

    Ateh, Comfort M.

    2015-01-01

    In evaluating teachers' instructional decisions during instruction, it is clear that the nature of their elicitation is crucial for student learning. When instructional decisions are informed by information about students' conceptual understanding, significant learning is possible. This article examined the elicitation practices of two high school…

  12. Elicited Emotions and Cognitive Functioning in Preschool Children

    ERIC Educational Resources Information Center

    Blau, Rivka; Klein, Pnina S.

    2010-01-01

    In this study, the effects of eliciting positive and negative emotions on various cognitive functions of four- to five-year-old preschool children were examined. Emotions were elicited through presentations of "happy" and "sad" video clips, before the children performed the cognitive tasks. Behavioural (facial expressions) and physiological (heart…

  13. Thermodynamics and Spontaneity

    NASA Astrophysics Data System (ADS)

    Ochs, Raymond S.

    1996-10-01

    Despite the importance of thermodynamics as the foundation of chemistry, most students emerge from introductory courses with only a dim understanding of this subject. Generally students recognize that the information is significant, yet do not assimilate it into later studies, especially in applied fields such as biology and biochemistry. A clear sense of the problem is reflected in a number of other contributions to this Journal (e.g., 1 - 6). Most (1 - 4, 6) recommend increased rigor in derivation of equations. This may appeal to students in advanced courses in chemical thermodynamics, but not to most. A few other suggestions are to introduce the subject earlier in general chemistry courses (2) or to provide innovative ways to visualize reaction changes (3). I suggest that the problem lies at another level entirely: the meanings of the terms are not clear. Recently, MacNeal (7) introduced the concept of mathsemantics, the joining of mathematics with a deep understanding of the sense (semantics) in which it operates. For example, the author argues that not only can we add apples and oranges (yielding total fruit), but that anything less than such a synthesis is trivial. Mathematics is hard, not because of the actual mathematical part of the problem but because of the semantics. As discussed thoroughly by Weinburg (8), the very names we affix to ideas dominate how we think about them. A similar reorientation would benefit chemical education. By way of example, the word "spontaneous" is widely used in thermodynamics, presumably because the word is familiar and assists understanding of this subject. In the following, I will provide evidence that this word has contributed more to the obfuscation of chemical ideas than it has helped elucidate them. Literature Cited 1. Redlich, O. J. Chem. Educ. 1975, 52, 374 - 376. 2. Bergquist, W.; Heikkinen, H. J. Chem. Educ. 1990, 67, 1000 - 1003. 3. Macomber, R. S. J. Chem. Educ. 1994, 71, 311 - 312. 4. Sanchez, K. S.; Vergenz, R

  14. Model based prediction of the existence of the spontaneous cochlear microphonic

    NASA Astrophysics Data System (ADS)

    Ayat, Mohammad; Teal, Paul D.

    2015-12-01

    In the mammalian cochlea, self-sustaining oscillation of the basilar membrane in the cochlea can cause vibration of the ear drum, and produce spontaneous narrow-band air pressure fluctuations in the ear canal. These spontaneous fluctuations are known as spontaneous otoacoustic emissions. Small perturbations in feedback gain of the cochlear amplifier have been proposed to be the generation source of self-sustaining oscillations of the basilar membrane. We hypothesise that the self-sustaining oscillation resulting from small perturbations in feedback gain produce spontaneous potentials in the cochlea. We demonstrate that according to the results of the model, a measurable spontaneous cochlear microphonic must exist in the human cochlea. The existence of this signal has not yet been reported. However, this spontaneous electrical signal could play an important role in auditory research. Successful or unsuccessful recording of this signal will indicate whether previous hypotheses about the generation source of spontaneous otoacoustic emissions are valid or should be amended. In addition according to the proposed model spontaneous cochlear microphonic is basically an electrical analogue of spontaneous otoacoustic emissions. In certain experiments, spontaneous cochlear microphonic may be more easily detected near its generation site with proper electrical instrumentation than is spontaneous otoacoustic emission.

  15. Cellular Stress Responses Elicited by Engineered Nanomaterials

    EPA Science Inventory

    Engineered nanomaterials are being incorporated continuously into consumer products, resulting in increased human exposures. The study of engineered nanomaterials has focused largely on oxidative stress and inflammation endpoints without further investigation of underlying pathwa...

  16. Engineered Nanomaterials Elicit Cellular Stress Responses

    EPA Science Inventory

    Engineered nanomaterials are being developed continuously and incorporated into consumer products, resulting in increased human exposures. The study of engineered nanomaterials has focused largely on toxicity endpoints without further investigating potential mechanisms or pathway...

  17. Spontaneous synchronization of arm motion between Japanese macaques.

    PubMed

    Nagasaka, Yasuo; Chao, Zenas C; Hasegawa, Naomi; Notoya, Tomonori; Fujii, Naotaka

    2013-01-01

    Humans show spontaneous synchronization of movements during social interactions; this coordination has been shown to facilitate smooth communication. Although human studies exploring spontaneous synchronization are increasing in number, little is known about this phenomenon in other species. In this study, we examined spontaneous behavioural synchronization between monkeys in a laboratory setting. Synchronization was quantified by changes in button-pressing behaviour while pairs of monkeys were facing one another. Synchronization between the monkeys was duly observed and it was participant-partner dependent. Further tests confirmed that the speed of button pressing changed to harmonic or sub-harmonic levels in relation to the partner's speed. In addition, the visual information from the partner induced a higher degree of synchronization than auditory information. This study establishes advanced tasks for testing social coordination in monkeys, and illustrates ways in which monkeys coordinate their actions to establish synchronization.

  18. Spontaneous regression of a cervical intraspinal cyst in a dog.

    PubMed

    Kamishina, Hiroaki; Ogawa, Hiroya; Katayama, Masaaki; Yasuda, Jun; Sato, Reeko; Tohyama, Koujiro

    2010-03-01

    We report a cervical intraspinal cyst in a dog that was initially tetraparetic but spontaneously recovered completely. MRI revealed a well-demarcated intraspinal cyst located dorsally to a degenerated intervertebral disc. The location of the cyst and its signal features on MRI resembled those of discal cysts previously reported in humans. It has been reported in dogs that clinical signs of a intraspinal cyst are similar to those of intervertebral disc herniation and both conditions require surgical intervention. Unexpectedly, our case showed rapid spontaneous recovery and the follow-up MRI revealed complete resolution of the intraspinal cyst and spinal cord compression. Spontaneous recovery of degenerative intraspinal cyst may occur in dogs, similar to rare human cases as reported previously. PMID:19952512

  19. Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice.

    PubMed

    Escolano, Amelia; Steichen, Jon M; Dosenovic, Pia; Kulp, Daniel W; Golijanin, Jovana; Sok, Devin; Freund, Natalia T; Gitlin, Alexander D; Oliveira, Thiago; Araki, Tatsuya; Lowe, Sarina; Chen, Spencer T; Heinemann, Jennifer; Yao, Kai-Hui; Georgeson, Erik; Saye-Francisco, Karen L; Gazumyan, Anna; Adachi, Yumiko; Kubitz, Michael; Burton, Dennis R; Schief, William R; Nussenzweig, Michel C

    2016-09-01

    A vaccine that elicits broadly neutralizing antibodies (bNAbs) against HIV-1 is likely to be protective, but this has not been achieved. To explore immunization regimens that might elicit bNAbs, we produced and immunized mice expressing the predicted germline PGT121, a bNAb specific for the V3-loop and surrounding glycans on the HIV-1 spike. Priming with an epitope-modified immunogen designed to activate germline antibody-expressing B cells, followed by ELISA-guided boosting with a sequence of directional immunogens, native-like trimers with decreasing epitope modification, elicited heterologous tier-2-neutralizing responses. In contrast, repeated immunization with the priming immunogen did not. Antibody cloning confirmed elicitation of high levels of somatic mutation and tier-2-neutralizing antibodies resembling the authentic human bNAb. Our data establish that sequential immunization with specifically designed immunogens can induce high levels of somatic mutation and shepherd antibody maturation to produce bNAbs from their inferred germline precursors. PMID:27610569

  20. Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice.

    PubMed

    Escolano, Amelia; Steichen, Jon M; Dosenovic, Pia; Kulp, Daniel W; Golijanin, Jovana; Sok, Devin; Freund, Natalia T; Gitlin, Alexander D; Oliveira, Thiago; Araki, Tatsuya; Lowe, Sarina; Chen, Spencer T; Heinemann, Jennifer; Yao, Kai-Hui; Georgeson, Erik; Saye-Francisco, Karen L; Gazumyan, Anna; Adachi, Yumiko; Kubitz, Michael; Burton, Dennis R; Schief, William R; Nussenzweig, Michel C

    2016-09-01

    A vaccine that elicits broadly neutralizing antibodies (bNAbs) against HIV-1 is likely to be protective, but this has not been achieved. To explore immunization regimens that might elicit bNAbs, we produced and immunized mice expressing the predicted germline PGT121, a bNAb specific for the V3-loop and surrounding glycans on the HIV-1 spike. Priming with an epitope-modified immunogen designed to activate germline antibody-expressing B cells, followed by ELISA-guided boosting with a sequence of directional immunogens, native-like trimers with decreasing epitope modification, elicited heterologous tier-2-neutralizing responses. In contrast, repeated immunization with the priming immunogen did not. Antibody cloning confirmed elicitation of high levels of somatic mutation and tier-2-neutralizing antibodies resembling the authentic human bNAb. Our data establish that sequential immunization with specifically designed immunogens can induce high levels of somatic mutation and shepherd antibody maturation to produce bNAbs from their inferred germline precursors.

  1. The common Cryptococcus neoformans glucuronoxylomannan M2 motif elicits non-protective antibodies

    PubMed Central

    Nakouzi, Antonio; Zhang, Tong; Oscarson, Stefan; Casadevall, Arturo

    2009-01-01

    The Cryptococcus neoformans capsular glucuronoxylomannan (GXM) is a potential vaccine antigen that can elicit protective and non-protective antibodies. In an attempt to focus the immune response on a single antigenic component, a heptasaccharide oligosaccharide representing the major structural motif (M2) of the most common clinical isolate was synthesized and conjugated to Human serum albumin (HSA). Monoclonal antibodies (mAbs) generated from mice immunized with M2-HSA produced the characteristic punctuate immunofluorescence associated with non-protective mAbs. None of the mAbs elicited by M2 immunization were opsonic. Passive administration of mAbs elicited by M2-HSA was not protective and there was no difference in the survival of mice immunized with M2-HSA and HSA. Hence, we conclude that the M2 motif represents an antigenic determinant in C. neoformans GXM that elicits non-protective responses and is not a suitable vaccine candidate. Furthermore, the results illustrate the first molecular assignment of a C. neoformans polysaccharide epitope and suggest a general strategy for the identification of GXM epitopes. PMID:19464529

  2. Optical antenna enhanced spontaneous emission

    PubMed Central

    Eggleston, Michael S.; Messer, Kevin; Zhang, Liming; Yablonovitch, Eli; Wu, Ming C.

    2015-01-01

    Atoms and molecules are too small to act as efficient antennas for their own emission wavelengths. By providing an external optical antenna, the balance can be shifted; spontaneous emission could become faster than stimulated emission, which is handicapped by practically achievable pump intensities. In our experiments, InGaAsP nanorods emitting at ∼200 THz optical frequency show a spontaneous emission intensity enhancement of 35× corresponding to a spontaneous emission rate speedup ∼115×, for antenna gap spacing, d = 40 nm. Classical antenna theory predicts ∼2,500× spontaneous emission speedup at d ∼ 10 nm, proportional to 1/d2. Unfortunately, at d < 10 nm, antenna efficiency drops below 50%, owing to optical spreading resistance, exacerbated by the anomalous skin effect (electron surface collisions). Quantum dipole oscillations in the emitter excited state produce an optical ac equivalent circuit current, Io = qω|xo|/d, feeding the antenna-enhanced spontaneous emission, where q|xo| is the dipole matrix element. Despite the quantum-mechanical origin of the drive current, antenna theory makes no reference to the Purcell effect nor to local density of states models. Moreover, plasmonic effects are minor at 200 THz, producing only a small shift of antenna resonance frequency. PMID:25624503

  3. Let the man choose what to do: Neural correlates of spontaneous lying and truth-telling.

    PubMed

    Yin, Lijun; Reuter, Martin; Weber, Bernd

    2016-02-01

    Many previous functional magnetic resonance imaging (fMRI) studies on deception used a paradigm of "instructed lies", which is different than other, more spontaneous forms of lying behavior. The present study aimed to investigate the neural processes underlying spontaneous and instructed lying and truth-telling, and to investigate the different mechanisms involved. This study used a modified sic bo gambling game with real payoffs in order to induce lying. In the spontaneous sessions, the participants themselves decided whether or not to lie, whereas in the instructed sessions they were explicitly told to respond either honestly or dishonestly. In the spontaneous lying (vs. truth-telling) condition, the subgenual anterior cingulate cortex (sACC) showed significantly higher activity, whereas the right dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC) and inferior parietal lobule (IPL) were more strongly activated when participants spontaneously told the truth (vs. lied). Our results suggest that the extra cognitive control required for suppressing the self-interest motives in spontaneous truth-telling is associated with higher activity in the fronto-parietal network, while the process of negative emotion in spontaneous lying induced greater involvement of the sACC. Although similar to spontaneous deception, instructed deception engenders greater involvement of the right inferior frontal gyrus (IFG), left supplementary motor area (SMA), anterior cingulate cortex (ACC), IPL and superior frontal gyrus (SFG) compared to baseline, instructed decisions did not elicit similar activation patterns in the regions of sACC, DLPFC, VLPFC and IPL which were sensitive to either spontaneous truth-telling or lying.

  4. Intraspleen DNA inoculation elicits protective cellular immune responses.

    PubMed

    Cano, A; Fragoso, G; Gevorkian, G; Terrazas, L I; Petrossian, P; Govezensky, T; Sciutto, E; Manoutcharian, K

    2001-04-01

    DNA immunization or inoculation is a recent vaccination method that induces both humoral and cellular immune responses in a range of hosts. Independent of the route or site of vaccination, the transfer of antigen-presenting cells (APC) or antigens into lymphoid organs is necessary. The aim of this investigation was to test whether intraspleen (i.s.) DNA inoculation is capable of inducing a protective immune response. We immunized mice by a single i.s. injection of a DNA construct expressing the immunoglobulin (Ig) heavy-chain variable domain (VH) in which the complementarity-determining regions (CDR) had been replaced by a Taenia crassiceps T-cell epitope. In these mice, immune responses and protective effects elicited by the vaccine were measured. We have shown here for the first time that i.s. DNA inoculation can induce protective cellular immune responses and activate CD8(+) T cells. Also, Ig V(H) appeared to be the minimal delivery unit of "antigenized" Ig capable of inducing T-cell activation in a lymphoid organ. The strategy of introducing T-cell epitopes into the molecular context of the V(H) domain in combination with i.s. DNA immunization could have important implications and applications for human immunotherapy.

  5. [Three cases of spontaneous pneumomediastinum].

    PubMed

    Kobayashi, Kashin; Tachikawa, Soichi; Horiguchi, Takahiko; Kondo, Rieko; Shiga, Mamoru; Hirose, Masahiro; Sasaki, Yasushi; Torigoe, Hiroshi

    2006-04-01

    We encountered 3 male patients with spontaneous pneumomediastinum. The patients were a 16-year old and a 17-year old and a 24-year old. Predisposing episodes for the development of spontaneous pneumomediastinum could be identified in all 3 patients: throwing a ball during a baseball game in 1, lifting a heavy load during work in 2. However, they were healthy and suddenly developed symptoms in the absence of any underlying disease. The presenting complaint was chest pain in all 3 patients. Chest X-ray films and chest CT images revealed pneumomediastinum. A diagnosis of spontaneous pneumomediastinum was made based on chest X-ray films and chest CT images. After conservative treatment, all 3 patients recovered.

  6. Prosodic marking, pitch and intensity in spontaneous lexical self-repair in dutch.

    PubMed

    Plug, Leendert; Carter, Paul

    2013-01-01

    This paper presents results of a phonetic analysis of instances of lexical self-repair drawn from a corpus of spontaneous Dutch speech. The analysis addresses questions concerning the phonetic details of prosodic marking in self-repair and its conditioning factors. In particular, it examines the relevance of semantic, temporal and frequency-related factors in modelling f0 and intensity measures and auditory judgements of whether repairs are prosodically marked. It addresses the extent to which observations made in studies using experimentally-elicited speech can be expected to generalise to repairs drawn from uncontrolled spontaneous speech. The results suggest that prosodic marking is rare in spontaneous lexical self-repair, and that semantic, temporal and frequency factors play a limited role only in conditioning speakers' choices for or against prosodic marking, although several weak tendencies can be observed. PMID:24281064

  7. Spontaneous Analog Number Representations in 3-Year-Old Children

    ERIC Educational Resources Information Center

    Cantlon, Jessica F.; Safford, Kelley E.; Brannon, Elizabeth M.

    2010-01-01

    When enumerating small sets of elements nonverbally, human infants often show a set-size limitation whereby they are unable to represent sets larger than three elements. This finding has been interpreted as evidence that infants spontaneously represent small numbers with an object-file system instead of an analog magnitude system (Feigenson,…

  8. Memory Errors Reveal a Bias to Spontaneously Generalize to Categories

    ERIC Educational Resources Information Center

    Sutherland, Shelbie L.; Cimpian, Andrei; Leslie, Sarah-Jane; Gelman, Susan A.

    2015-01-01

    Much evidence suggests that, from a young age, humans are able to generalize information learned about a subset of a category to the category itself. Here, we propose that--beyond simply being able to perform such generalizations--people are "biased" to generalize to categories, such that they routinely make spontaneous, implicit…

  9. Spontaneous Fission: A Kinetic Approach

    SciTech Connect

    Bonasera, A.; Iwamoto, A.; Bonasera, A.

    1997-01-01

    We present an attempt towards the many-body description of spontaneous fission based on the semiclassical Vlasov equation and the Feynman path integral method. We define suitable collective variables from the Vlasov solution and use the imaginary time technique for the dynamics below the Coulomb barrier. We demonstrate (1) the stability of the Vlasov solution, (2) the ability of this model to calculate the basic features of the whole spontaneous fission process, (3) the sensitivity of the dynamics below the barrier to the mean field potential, and (4) the important role of collective excitations and of particle emission during the fission process. {copyright} {ital 1997} {ital The American Physical Society}

  10. Spontaneous rupture of the ureter.

    PubMed

    Eken, Alper; Akbas, Tugana; Arpaci, Taner

    2015-02-01

    Spontaneous rupture of the ureter is a very rare condition and usually results from ureteral obstruction by a calculus. Only theoretical mechanisms have been proposed and no possible explanation has yet been reported in the literature. Intravenous contrast-enhanced computed tomography is the most informative study with high sensitivity. Treatment should be individualised, and depends on the state of the patient. Minimally invasive endourological procedures with double-J catheter placement and percutaneous drainage offer excellent results. Conservative management with analgesics and antibiotic coverage may be an alternative to surgery. Herein, we present a case of spontaneous rupture of the proximal ureter with no evidence of an underlying pathological condition.

  11. Spontaneous cervical and mediastinal emphysema.

    PubMed

    Parker, G S; Mosborg, D A; Foley, R W; Stiernberg, C M

    1990-09-01

    Subcutaneous cervical emphysema often appears as a result of surgery or trauma. However, when it occurs spontaneously, the patient may present with clinically impressive and dramatic features. The etiology is related to the rupture of terminal alveoli and dissection of air along the pulmonary vasculature. Exercise may contribute to the process by increases in intrathoracic pressure. Six cases of spontaneous cervical emphysema, all related to SCUBA diving training at a Naval facility, were recently seen at our institution. Proper management entails having a high index of suspicion for diagnosis, and then being able to identify potentially life-threatening complications.

  12. Flow Friction or Spontaneous Ignition?

    NASA Technical Reports Server (NTRS)

    Stoltzfus, Joel M.; Gallus, Timothy D.; Sparks, Kyle

    2012-01-01

    "Flow friction," a proposed ignition mechanism in oxygen systems, has proved elusive in attempts at experimental verification. In this paper, the literature regarding flow friction is reviewed and the experimental verification attempts are briefly discussed. Another ignition mechanism, a form of spontaneous combustion, is proposed as an explanation for at least some of the fire events that have been attributed to flow friction in the literature. In addition, the results of a failure analysis performed at NASA Johnson Space Center White Sands Test Facility are presented, and the observations indicate that spontaneous combustion was the most likely cause of the fire in this 2000 psig (14 MPa) oxygen-enriched system.

  13. Comparison of evoked vs. spontaneous tics in a patient with trigeminal neuralgia (tic doloureux).

    PubMed

    Borsook, David; Moulton, Eric A; Pendse, Gautam; Morris, Susie; Cole, Sadie H; Aiello-Lammens, Matthew; Scrivani, Steven; Becerra, Lino R

    2007-11-06

    A 53-year old woman with tic doloureaux, affecting her right maxillary division of the trigeminal nerve (V2), could elicit shooting pains by slightly tapping her teeth when off medication. The pains, which she normally rated as > 6/10 on a visual analog scale (VAS), were electric shock-like in nature. She had no other spontaneous or ongoing background pain affecting the region. Based on her ability to elicit these tics, functional magnetic resonance imaging (fMRI) was performed while she produced brief shocks every 2 minutes on cue (evoked pain) over a 20 min period. In addition, she had 1-2 spontaneous shocks manifested between these evoked pains over the course of functional image acquisition. Increased fMRI activation for both evoked and spontaneous tics was observed throughout cortical and subcortical structures commonly observed in experimental pain studies with healthy subjects; including the primary somatosensory cortex, insula, anterior cingulate, and thalamus. Spontaneous tics produced more decrease in signals in a number of regions including the posterior cingulate cortex and amygdala, suggesting that regions known to be involved in expectation/anticipation may have been activated for the evoked, but not spontaneous, tics. In this patient there were large increases in activation observed in the frontal regions, including the anterior cingulate cortex and the basal ganglia. Spontaneous tics showed increased activation in classic aversion circuitry that may contribute to increased levels of anxiety. We believe that this is the first report of functional imaging of brain changes in tic-doloureaux.

  14. Comparison of evoked vs. spontaneous tics in a patient with trigeminal neuralgia (tic doloureux)

    PubMed Central

    2007-01-01

    A 53-year old woman with tic doloureaux, affecting her right maxillary division of the trigeminal nerve (V2), could elicit shooting pains by slightly tapping her teeth when off medication. The pains, which she normally rated as > 6/10 on a visual analog scale (VAS), were electric shock-like in nature. She had no other spontaneous or ongoing background pain affecting the region. Based on her ability to elicit these tics, functional magnetic resonance imaging (fMRI) was performed while she produced brief shocks every 2 minutes on cue (evoked pain) over a 20 min period. In addition, she had 1–2 spontaneous shocks manifested between these evoked pains over the course of functional image acquisition. Increased fMRI activation for both evoked and spontaneous tics was observed throughout cortical and subcortical structures commonly observed in experimental pain studies with healthy subjects; including the primary somatosensory cortex, insula, anterior cingulate, and thalamus. Spontaneous tics produced more decrease in signals in a number of regions including the posterior cingulate cortex and amygdala, suggesting that regions known to be involved in expectation/anticipation may have been activated for the evoked, but not spontaneous, tics. In this patient there were large increases in activation observed in the frontal regions, including the anterior cingulate cortex and the basal ganglia. Spontaneous tics showed increased activation in classic aversion circuitry that may contribute to increased levels of anxiety. We believe that this is the first report of functional imaging of brain changes in tic-doloureaux. PMID:17983481

  15. Dynamics of spontaneous otoacoustic emissions

    NASA Astrophysics Data System (ADS)

    Bergevin, Christopher; Salerno, Anthony

    2015-12-01

    Spontaneous otoacoustic emissions (SOAEs) have become a hallmark feature in modern theories of an `active' inner ear, given their numerous correlations to auditory function (e.g., threshold microstructure, neurophysiological tuning curves), near universality across tetrapod classes, and physiological correlates at the single hair cell level. However, while several different classes of nonlinear models exist that describe the mechanisms underlying SOAE generation (e.g., coupled limit-cycle oscillators, global standing waves), there is still disagreement as to precisely which biophysical concepts are at work. Such is further compounded by the idiosyncratic nature of SOAEs: Not all ears emit, and when present, SOAE activity can occur at seemingly arbitrary frequencies (though always within the most sensitive range of the audiogram) and in several forms (e.g., peaks, broad `baseline' plateaus). The goal of the present study was to develop new signal processing and stimulation techniques that would allow for novel features of SOAE activity to be revealed. To this end, we analyzed data from a variety of different species: human, lizard, and owl. First, we explored several strategies for examining SOAE waveforms in the absence of external stimuli to further ascertain what constitutes `self-sustained sinusoids' versus `filtered noise'. We found that seemingly similar peaks in the spectral domain could exhibit key differences in the time domain, which we interpret as providing critical information about the underlying oscillators and their coupling. Second, we introduced dynamic stimuli (swept-tones, tone bursts) at a range of levels, whose interaction with SOAEs could be visualized in the time-frequency domain. Aside from offering a readily accessible way to visualize many previously reported effects (e.g., entrainment, facilitation), we observed several new features such as subharmonic distortion generation and competing pulling/pushing effects when multiple tones were

  16. CCSI Risk Estimation: An Application of Expert Elicitation

    SciTech Connect

    Engel, David W.; Dalton, Angela C.

    2012-10-01

    The Carbon Capture Simulation Initiative (CCSI) is a multi-laboratory simulation-driven effort to develop carbon capture technologies with the goal of accelerating commercialization and adoption in the near future. One of the key CCSI technical challenges is representing and quantifying the inherent uncertainty and risks associated with developing, testing, and deploying the technology in simulated and real operational settings. To address this challenge, the CCSI Element 7 team developed a holistic risk analysis and decision-making framework. The purpose of this report is to document the CCSI Element 7 structured systematic expert elicitation to identify additional risk factors. We review the significance of and established approaches to expert elicitation, describe the CCSI risk elicitation plan and implementation strategies, and conclude by discussing the next steps and highlighting the contribution of risk elicitation toward the achievement of the overarching CCSI objectives.

  17. Spoonerisms as Sequencer Conflicts: Evidence from Artifically Elicited Errors

    ERIC Educational Resources Information Center

    Baars, Bernard J.; Motley, Michael T.

    1976-01-01

    Presents evidence that spoonerisms result from a conflict in word sequencing that carries through to phoneme sequencing, and in the process illustrates the use of some techniques for the experimental elicitation of spoonerisms. (Author/RK)

  18. Songbirds possess the spontaneous ability to discriminate syntactic rules.

    PubMed

    Abe, Kentaro; Watanabe, Dai

    2011-08-01

    Whether the computational systems in language perception involve specific abilities in humans is debated. The vocalizations of songbirds share many features with human speech, but whether songbirds possess a similar computational ability to process auditory information as humans is unknown. We analyzed their spontaneous discrimination of auditory stimuli and found that the Bengalese finch (Lonchura striata var. domestica) can use the syntactical information processing of syllables to discriminate songs). These finches were also able to acquire artificial grammatical rules from synthesized syllable strings and to discriminate novel auditory information according to them. We found that a specific brain region was involved in such discrimination and that this ability was acquired postnatally through the encounter with various conspecific songs. Our results indicate that passerine songbirds spontaneously acquire the ability to process hierarchical structures, an ability that was previously supposed to be specific to humans. PMID:21706017

  19. The new vaccines: building viruses that elicit antitumor immunity

    PubMed Central

    Restifo, Nicholas P

    2007-01-01

    Whereas cancer cells are poor immunogens, some viruses are capable of eliciting powerful and lifelong immunity. Recombinant viruses and plasmid DNA encoding tumor-associated antigens can elicit powerful and specific immune responses that can be enhanced by the use of cytokines and costimulatory molecules. These immune responses have destroyed growing tumor cells in experimental animal models. For the first time, immunotherapeutic strategies that employ recombinant viruses are being tested in clinical trials with cancer patients. PMID:8902391

  20. Determination of the spontaneous locomotor activity in Drosophila melanogaster.

    PubMed

    Woods, Jared K; Kowalski, Suzanne; Rogina, Blanka

    2014-01-01

    Drosophila melanogaster has been used as an excellent model organism to study environmental and genetic manipulations that affect behavior. One such behavior is spontaneous locomotor activity. Here we describe our protocol that utilizes Drosophila population monitors and a tracking system that allows continuous monitoring of the spontaneous locomotor activity of flies for several days at a time. This method is simple, reliable, and objective and can be used to examine the effects of aging, sex, changes in caloric content of food, addition of drugs, or genetic manipulations that mimic human diseases. PMID:24747955

  1. Spontaneous haemoperitoneum from surreptitious ingestion of a rodenticide.

    PubMed

    Soubiron, L; Hantson, P; Michaux, I; Lambert, M; Mahieu, P; Pringot, J

    2000-12-01

    Superwarfarins have progressively replaced warfarin as rodenticides as they are more potent and have a longer anticoagulant activity. Human exposure may be complicated by spontaneous haemorrhage in various sites. We report the case of a 51-year-old woman who was admitted with spontaneous haemoperitoneum and intramural haematoma along the small intestine. After the evidence of a deficit of vitamin K1-dependent clotting factors (II, VII, IX, X), the patient admitted that she was chronically ingesting difenacoum. She was successfully treated with fresh frozen plasma and vitamin K1. Follow-up was not accepted. PMID:11764142

  2. Chemical pleurodesis for spontaneous pneumothorax.

    PubMed

    How, Cheng-Hung; Hsu, Hsao-Hsun; Chen, Jin-Shing

    2013-12-01

    Pneumothorax is defined as the presence of air in the pleural cavity. Spontaneous pneumothorax, occurring without antecedent traumatic or iatrogenic cause, is sub-divided into primary and secondary. The severity of pneumothorax could be varied from asymptomatic to hemodynamically compromised. Optimal management of this benign disease has been a matter of debate. In addition to evacuating air from the pleural space by simple aspiration or chest tube drainage, the management of spontaneous pneumothorax also focused on ceasing air leakage and preventing recurrences by surgical intervention or chemical pleurodesis. Chemical pleurodesis is a procedure to achieve symphysis between the two layers of pleura by sclerosing agents. In the current practice guidelines, chemical pleurodesis is reserved for patients unable or unwilling to receive surgery. Recent researches have found that chemical pleurodesis is also safe and effective in preventing pneumothorax recurrence in patients with the first episode of spontaneous pneumothorax or after thoracoscopic surgery and treating persistent air leakage after thoracoscopic surgery. In this article we aimed at exploring the role of chemical pleurodesis for spontaneous pneumothorax, including ceasing air leakage and preventing recurrence. The indications, choice of sclerosants, safety, effects, and possible side effects or complications of chemical pleurodesis are also reviewed here.

  3. Smoking habits and spontaneous abortion.

    PubMed

    Sandahl, B

    1989-04-01

    Smoking habits have been compared in three samples of pregnancies: (1) spontaneous abortions (n = 610); (2) induced abortions (n = 800); and (3) deliveries (n = 1337). The variables studied were, besides smoking habits, day of LMP, outcome of earlier pregnancies, maternal age, and, for the delivery sample, also diagnoses of mother and child, gestational length, sex, and birthweight. A statistical analysis of the association between smoking and the risk of having a spontaneous abortion was made. The comparisons were made with all types of intra-uterine pregnancies but spontaneous abortions, e.g., deliveries and induced abortions. The effects and consequences of that are discussed. The smoking rates according to pregnancy outcome differ among the samples. In the induced abortion sample 58% smoked compared with 50% in the spontaneous abortion sample and 44% in the delivery sample. The well-known effect of smoking on gestational length and birthweight was shown. No significant effect of smoking on the miscarriage risk was seen. The only trend was the opposite. Possible explanations for this are discussed.

  4. Toddlers' Spontaneous Attention to Number

    ERIC Educational Resources Information Center

    Baroody, Arthur J.; Li, Xia; Lai, Meng-lung

    2008-01-01

    Hannula and Lehtinen (2001, 2005) defined spontaneous focusing on numerosity (SFON) as the tendency to notice the relatively abstract attribute of number despite the presence of other attributes. According to nativists, an innate concept of one to three directs young children's attention to these "intuitive numbers" in everyday situations--even…

  5. Student Experiments in Spontaneous Fission.

    ERIC Educational Resources Information Center

    Becchetti, F. D.; Ying, J. S.

    1981-01-01

    Advanced undergraduate experiments utilizing a commercially available, thin spontaneous fission source are described, including studies of the energy and mass distribution of the fission fragments and their energy and angular correlation. The experiments provide a useful introduction to fission, nuclear mass equations, heavy-ion physics, and…

  6. Spontaneous bilateral quadriceps tendon rupture.

    PubMed

    Vigneswaran, N; Lee, K; Yegappan, M

    2007-11-01

    Spontaneous bilateral quadriceps tendon ruptures are uncommon. We present a 30-year-old man with end-stage renal failure, who sustained this injury, and subsequently had surgical repair of both tendons on separate occasions. He has since regained full range of movement of both knees.

  7. Electrophysiological and hemolytic activity elicited by the venom of the jellyfish Cassiopea xamachana.

    PubMed

    Torres, M; Aguilar, M B; Falcón, A; Sánchez, L; Radwan, F F; Burnett, J W; Heimer-de la Cotera, E P; Arellano, R O

    2001-09-01

    In this study, we determined hemolysis activity in human and sheep erythrocytes, and characterized the electrical responses in Xenopus oocyte membrane elicited by the venom of the jellyfish Cassiopea xamachana (Cx). The Cx venom produced hemolysis in both species, being more potent on human red cells. The electrophysiological study showed that the Cx venom elicited three different responses in the oocytes. One current was generated in all the oocytes tested and corresponded with a slow inward current (I(Cx)) associated with an increase in membrane conductance. I(Cx) was concentration-dependent and had a reversal potential of -10.3+/-0.4 mV. Ionic substitution studies indicated that the conductive pathway was mainly permeable to cations and non-selective. The oocyte membrane resistance was completely recovered after washout of the venom, this suggested that the effect was due to generation of a specific membrane conductance as opposed to a possible non-specific membrane breakdown. A comparative study with three distinct native cationic channels present in the oocyte membrane [i.e. (1) hemi-gap-junction channels, (2) mechanosensitive channels, and (3) the ouabain-sensitive channel activated by palytoxin], showed that I(Cx) might correspond to opening of mechanosensitive channels or to activation of an unknown cationic channel located in the oocyte membrane. The bioactive fraction eliciting I(Cx) were peptides and was separated from two other peptidic hemolytic fractions by chromatography. PMID:11384717

  8. Influence of gravity on the eye movement response elicited by periodic lateral linear acceleration.

    PubMed

    Hashiba, M; Wetzig, J; v Baumgarten, R; Watanabe, S; Baba, S

    1993-12-01

    Periodic linear acceleration elicits eye movements in human beings. This is generally considered to be the result of the otolithic-ocular reflex (OOR). However, otolith organs respond not only to the resultant inertial force caused by head motion, but also to the gravitational force. We investigated the influence of the resultant gravito-inertial vector on the OOR using a linear acceleration sled. Subjects were 10 healthy volunteers. The sled moving back and forth parallel to the lateral head axis stimulated the subjects. We tested each subject in 7 different positions in the pitch plane. Horizontal eye movements with nystagmic patterns were elicited by these stimuli. The results indicate that the responses were larger in the forward tilted positions than in the backward tilted positions. It can be concluded that the horizontal OOR is influenced by the gravity vector. The cause of this phenomenon is still unclear. However, it could be closely related to the nystagmus observed during off vertical axis rotation.

  9. Spontaneous tempo and rhythmic entrainment in a bonobo (Pan paniscus).

    PubMed

    Large, Edward W; Gray, Patricia M

    2015-11-01

    The emergence of speech and music in the human species represent major evolutionary transitions that enabled the use of complex, temporally structured acoustic signals to coordinate social interaction. While the fundamental capacity for temporal coordination with complex acoustic signals has been shown in a few distantly related species, the extent to which nonhuman primates exhibit sensitivity to auditory rhythms remains controversial. In Experiment 1, we assessed spontaneous motor tempo and tempo matching in a bonobo (Pan paniscus), in the context of a social drumming interaction. In Experiment 2, the bonobo spontaneously entrained and synchronized her drum strikes within a range around her spontaneous motor tempo. Our results are consistent with the hypothesis that the evolution of acoustic communication builds upon fundamental neurodynamic mechanisms that can be found in a wide range of species, and are recruited for social interactions.

  10. Spontaneous tempo and rhythmic entrainment in a bonobo (Pan paniscus).

    PubMed

    Large, Edward W; Gray, Patricia M

    2015-11-01

    The emergence of speech and music in the human species represent major evolutionary transitions that enabled the use of complex, temporally structured acoustic signals to coordinate social interaction. While the fundamental capacity for temporal coordination with complex acoustic signals has been shown in a few distantly related species, the extent to which nonhuman primates exhibit sensitivity to auditory rhythms remains controversial. In Experiment 1, we assessed spontaneous motor tempo and tempo matching in a bonobo (Pan paniscus), in the context of a social drumming interaction. In Experiment 2, the bonobo spontaneously entrained and synchronized her drum strikes within a range around her spontaneous motor tempo. Our results are consistent with the hypothesis that the evolution of acoustic communication builds upon fundamental neurodynamic mechanisms that can be found in a wide range of species, and are recruited for social interactions. PMID:26147705

  11. Endocrine dysfunction and recurrent spontaneous abortion: An overview.

    PubMed

    Kaur, Ramandeep; Gupta, Kapil

    2016-01-01

    Miscarriage is the spontaneous loss of a fetus before it is viable, occurring at a rate of 15-20%. Recurrent spontaneous abortion (RSA) or habitual miscarriage is defined as repeated occurrence of 3 or more miscarriages before 20(th) week of gestation accounting for the most common complication of early pregnancy in humans. Various etiological factors responsible for recurrent miscarriage are anatomical, genetical, endocrinological, immunological, and infectious. The endocrinological abnormalities may be polycystic ovarian syndrome, hyperprolactinemia, luteal phase defect, thyroid dysfunction, diabetes, or hyperandrogenism contributing to recurrent pregnancy loss. In the present article, the role of endocrinological disorders in patients with RSA has been reviewed. The article search was done using electronic databases, Google scholarly articles, and PubMed based on different key words. We have further combined the searches and made grouping as per various endocrine abnormalities, which might be responsible to cause spontaneous loss of fetus. PMID:27127734

  12. Endocrine dysfunction and recurrent spontaneous abortion: An overview

    PubMed Central

    Kaur, Ramandeep; Gupta, Kapil

    2016-01-01

    Miscarriage is the spontaneous loss of a fetus before it is viable, occurring at a rate of 15–20%. Recurrent spontaneous abortion (RSA) or habitual miscarriage is defined as repeated occurrence of 3 or more miscarriages before 20th week of gestation accounting for the most common complication of early pregnancy in humans. Various etiological factors responsible for recurrent miscarriage are anatomical, genetical, endocrinological, immunological, and infectious. The endocrinological abnormalities may be polycystic ovarian syndrome, hyperprolactinemia, luteal phase defect, thyroid dysfunction, diabetes, or hyperandrogenism contributing to recurrent pregnancy loss. In the present article, the role of endocrinological disorders in patients with RSA has been reviewed. The article search was done using electronic databases, Google scholarly articles, and PubMed based on different key words. We have further combined the searches and made grouping as per various endocrine abnormalities, which might be responsible to cause spontaneous loss of fetus. PMID:27127734

  13. Endocrine dysfunction and recurrent spontaneous abortion: An overview.

    PubMed

    Kaur, Ramandeep; Gupta, Kapil

    2016-01-01

    Miscarriage is the spontaneous loss of a fetus before it is viable, occurring at a rate of 15-20%. Recurrent spontaneous abortion (RSA) or habitual miscarriage is defined as repeated occurrence of 3 or more miscarriages before 20(th) week of gestation accounting for the most common complication of early pregnancy in humans. Various etiological factors responsible for recurrent miscarriage are anatomical, genetical, endocrinological, immunological, and infectious. The endocrinological abnormalities may be polycystic ovarian syndrome, hyperprolactinemia, luteal phase defect, thyroid dysfunction, diabetes, or hyperandrogenism contributing to recurrent pregnancy loss. In the present article, the role of endocrinological disorders in patients with RSA has been reviewed. The article search was done using electronic databases, Google scholarly articles, and PubMed based on different key words. We have further combined the searches and made grouping as per various endocrine abnormalities, which might be responsible to cause spontaneous loss of fetus.

  14. Spontaneous non-verbal counting in toddlers.

    PubMed

    Sella, Francesco; Berteletti, Ilaria; Lucangeli, Daniela; Zorzi, Marco

    2016-03-01

    A wealth of studies have investigated numerical abilities in infants and in children aged 3 or above, but research on pre-counting toddlers is sparse. Here we devised a novel version of an imitation task that was previously used to assess spontaneous focusing on numerosity (i.e. the predisposition to grasp numerical properties of the environment) to assess whether pre-counters would spontaneously deploy sequential (item-by-item) enumeration and whether this ability would rely on the object tracking system (OTS) or on the approximate number system (ANS). Two-and-a-half-year-olds watched the experimenter performing one-by-one insertion of 'food tokens' into an opaque animal puppet and then were asked to imitate the puppet-feeding behavior. The number of tokens varied between 1 and 6 and each numerosity was presented many times to obtain a distribution of responses during imitation. Many children demonstrated attention to the numerosity of the food tokens despite the lack of any explicit cueing to the number dimension. Most notably, the response distributions centered on the target numerosities and showed the classic variability signature that is attributed to the ANS. These results are consistent with previous studies on sequential enumeration in non-human primates and suggest that pre-counting children are capable of sequentially updating the numerosity of non-visible sets through additive operations and hold it in memory for reproducing the observed behavior. PMID:25754974

  15. Cyclin B1 Vaccine Delays Spontaneous Tumors

    PubMed Central

    Laura A, Vella; Min, Yu; Amy, Phillips; Olivera J, Finn

    2012-01-01

    We previously identified cyclin B1-specific T cells and antibodies in cancer patients with cyclin B1+ tumors and also in some healthy individuals. We also demonstrated that these responses may be important in cancer immunosurveillance by showing that vaccination against cyclin B1 prevents growth of transplantable cyclin B1+ tumors in mice. Constitutive overexpression of cyclin B1 was determined to correlate with the lack of p53 function. This allowed us to use p53−/− mice as a model that better approximates human disease. p53−/− mice spontaneously develop cyclin B1+ tumors. At 5–6 weeks of age, when the mice were still healthy with no evidence of tumor, they received the cyclin B1 vaccine and were then observed for tumor growth. We demonstrate that cyclin B1 vaccination can delay spontaneous cyclin B1+ tumor growth and increases median survival of tumor bearing p53−/− mice. PMID:19769738

  16. Spontaneous repetitive thoughts can be adaptive: postscript on "mind wandering".

    PubMed

    Baars, Bernard J

    2010-03-01

    When researchers use the term mind wandering for task-unrelated thoughts in signal detection tasks, we may fall into the trap of believing that spontaneous thoughts are task unrelated in a deeper sense. Similar negative connotations are attached to common terms like cognitive failures, resting state, rumination, distraction, attentional failures, absent-mindedness, repetitiveness, mind lapses, going AWOL in the brain, cortical idling, and the like. Nevertheless, it seems obvious that mathematicians and scientists often engage in spontaneous repetitive thoughts and that the results of those thoughts are by no means maladaptive. Yet that seems to be implied by the standard use of common terms in the research literature. As humans, we know that spontaneous ideation goes on during all of our waking hours, during dreams and even in slow-wave sleep. It is unlikely that such a great allocation of mental resources has no useful adaptive function. This view of the spontaneous stream is consistent with the perspective of global workspace theory on conscious contents, which suggests that conscious events are not like unconscious cognitive representations. Rather, conscious events trigger widespread adaptive changes in the brain, far beyond their cortical origins. The brain evidence for such "global broadcasting" triggered by conscious (but not matched unconscious) events throughout the cortex is now quite compelling. Spontaneous conscious thoughts, even if they appear to be arbitrary, irrelevant, unwanted, or intrusive, may still play an important adaptive role in life-relevant problem solving and learning.

  17. Evaluating elicited anxiety in a simulated environment.

    PubMed

    Stredney, Don; Hittle, Brad; Sessanna, Dennis

    2008-01-01

    Simulated environments are increasingly being used to evaluate human behavior in a wide variety of situations. These virtual environments are particularly useful in the study of behavior involving dangerous conditions. Quantifying the impact of these environments on the subject is essential to validate the efficacy of the simulation as a virtualization of reality. We have developed a prototypical environment that simulates a common agricultural setting that provides the potential for acute injuries. We report on an exploratory study to evaluate the efficacy of our design to illicit a sense of realism and subsequently evoke a physiological response of anxiety in the subject. We present on the components that comprise the environment, our study design, and preliminary results.

  18. Diesel Exhaust Inhalation Elicits Acute Vasoconstriction in Vivo

    PubMed Central

    Peretz, Alon; Sullivan, Jeffrey H.; Leotta, Daniel F.; Trenga, Carol A.; Sands, Fiona N.; Allen, Jason; Carlsten, Chris; Wilkinson, Charles W.; Gill, Edward A.; Kaufman, Joel D.

    2008-01-01

    Background Traffic-related air pollution is consistently associated with cardiovascular morbidity and mortality. Recent human and animal studies suggest that exposure to air pollutants affects vascular function. Diesel exhaust (DE) is a major source of traffic-related air pollution. Objectives Our goal was to study the effects of short-term exposure to DE on vascular reactivity and on mediators of vascular tone. Methods In a double-blind, crossover, controlled exposure study, 27 adult volunteers (10 healthy and 17 with metabolic syndrome) were exposed in randomized order to filtered air (FA) and each of two levels of diluted DE (100 or 200 μg/m3 of fine particulate matter) in 2-hr sessions. Before and after each exposure, we assessed the brachial artery diameter (BAd) by B-mode ultrasound and collected blood samples for endothelin-1 (ET-1) and catecholamines. Postexposure we also assessed endothelium-dependent flow-mediated dilation (FMD). Results Compared with FA, DE at 200 μg/m3 elicited a decrease in BAd (0.11 mm; 95% confidence interval, 0.02–0.18), and the effect appeared linearly dose related with a smaller effect at 100 μg/m3. Plasma levels of ET-1 increased after 200 μg/m3 DE but not after FA (p = 0.01). There was no consistent impact of DE on plasma catecholamines or FMD. Conclusions These results demonstrate that short-term exposure to DE is associated with acute endothelial response and vasoconstriction of a conductance artery. Elucidation of the signaling pathways controlling vascular tone that underlie this observation requires further study. PMID:18629317

  19. Feeding-elicited cataplexy in orexin knockout mice

    PubMed Central

    Clark, Erika L.; Baumann, Christian R.; Cano, Georgina; Scammell, Thomas E.; Mochizuki, Takatoshi

    2009-01-01

    Mice lacking orexin/hypocretin signaling have sudden episodes of atonia and paralysis during active wakefulness. These events strongly resemble cataplexy, episodes of sudden muscle weakness triggered by strong positive emotions in people with narcolepsy, but it remains unknown whether murine cataplexy is triggered by positive emotions. To determine whether positive emotions elicit murine cataplexy, we placed orexin knockout (KO) mice on a scheduled feeding protocol with regular or highly palatable food. Baseline sleep/wake behavior was recorded with ad lib regular chow. Mice were then placed on a scheduled feeding protocol in which they received 60% of their normal amount of chow 3 hr after dark onset for the next 10 days. Wild-type and KO mice rapidly entrained to scheduled feeding with regular chow, with more wake and locomotor activity prior to the feeding time. On day 10 of scheduled feeding, orexin KO mice had slightly more cataplexy during the food-anticipation period and more cataplexy in the second half of the dark period, when they may have been foraging for residual food. To test whether more palatable food increases cataplexy, mice were then switched to scheduled feeding with an isocaloric amount of Froot Loops, a food often used as a reward in behavioral studies. With this highly palatable food, orexin KO mice had much more cataplexy during the food-anticipation period and throughout the dark period. The increase in cataplexy with scheduled feeding, especially with highly palatable food, suggests that positive emotions may trigger cataplexy in mice, just as in people with narcolepsy. Establishing this connection helps validate orexin KO mice as an excellent model of human narcolepsy and provides an opportunity to better understand the mechanisms that trigger cataplexy. PMID:19362119

  20. Laser Cooling without Spontaneous Emission

    NASA Astrophysics Data System (ADS)

    Corder, Christopher; Arnold, Brian; Metcalf, Harold

    2015-01-01

    This Letter reports the demonstration of laser cooling without spontaneous emission, and thereby addresses a significant controversy. It works by restricting the atom-light interaction to a time short compared to a cycle of absorption followed by natural decay. It is achieved by using the bichromatic force on an atomic transition with a relatively long excited state lifetime and a relatively short cooling time so that spontaneous emission effects are minimized. The observed width of the one-dimensional velocity distribution is reduced by ×2 thereby reducing the "temperature" by ×4 . Moreover, our results comprise a compression in phase space because the spatial expansion of the atomic sample is limited. This accomplishment is of interest to direct laser cooling of molecules or in experiments where working space or time is limited.

  1. Speeding up spontaneous disease extinction

    NASA Astrophysics Data System (ADS)

    Khasin, Michael

    2012-02-01

    The dynamics of epidemic in a susceptible population is affected both by the random character of interactions between the individuals and by environmental variations. As a consequence, the sizes of the population groups (infected, susceptible, etc.) fluctuate in the course of evolution of the epidemic. In a small community a rare large fluctuation in the number of infected can result in extinction of the disease. We suggest a novel paradigm of controlling the epidemic, where the control field, such as vaccination, is designed to maximize the rate of spontaneous disease extinction. We show that, for a limited-scope vaccination, the optimal vaccination protocol and its impact on the epidemics have universal features: (i) the vaccine must be applied in pulses, (ii) the spontaneous disease extinction is synchronized with the vaccination. We trace this universality to general properties of the response of large fluctuations to external perturbations.

  2. Spontaneous internal carotid artery dissection.

    PubMed

    Khimenko, L P; Esham, H R; Ahmed, W

    2000-10-01

    Once considered uncommon, spontaneous dissection of the carotid artery is an increasingly recognized cause of stroke, headache, cranial nerve palsy, or ophthalmologic events, especially in young adults. Even in the presence of existing signs and symptoms, the diagnosis can be missed by experienced physicians of all specialties. We report a case of spontaneous internal carotid artery dissection in a 38-year-old woman with a cortical stroke and visual disturbances as initial symptoms. The diagnosis was confirmed by magnetic resonance imaging/angiography and by angiography. Prompt anticoagulation was instituted, and the patient had complete resolution of symptoms. Cervicocephalic arterial dissection should be included in the differential diagnosis of the causes of cerebrovascular events.

  3. [Effects of trimebutine maleate (TM-906) on the spontaneous contraction of the isolated guinea pig stomach].

    PubMed

    Takenaga, H; Magaribuchi, T; Tamaki, H

    1982-08-01

    Effects of trimebutine maleate (TM-906) on the spontaneous contraction were investigated in the isolated circular smooth muscle of the antrum region of the guinea pig stomach. TM-906 dose-dependently reduced the amplitude of the regular spontaneous contraction without any marked change in its frequency and basal tension. This effect of TM-906 was also observed in the presence of phentolamine, propranolol, atropine, and tetrodotoxin. However, the inhibitory effect of TM-906 was overcome by increasing the extracellular concentration of CaCl2. On the other hand, in preparations which exhibited irregular spontaneous contraction, TM-906 regularized it, and spontaneous contraction with regular frequency and amplitude was elicited. In addition, this regularizing effect of TM-906 was also observed in the presence of atropine and tetrodotoxin. It was concluded that TM-906 has dual effects on the spontaneous contraction, reducing the amplitude of regular contraction and regularizing the irregular contraction. These effects of TM-906 may be attributed to the direct action on the smooth muscle. PMID:7173739

  4. Spontaneous shrinkage of vestibular schwannoma

    PubMed Central

    Romani, Rossana; Pollock, Jonathan

    2016-01-01

    Background: “Watch, wait, and rescan” (WWR) has an established place as a successful management option for a significant proportion of vestibular schwannomas (VS) as an alternative to microsurgical removal or stereotactic radiotherapy. VS may grow slowly and continuously, followed by stagnation or even shrinkage. We present two case reports of spontaneous shrinkage of VS along with a review of the literature. Case Description: A 29-year-old female presented with a progressive history of visual blurring and intermittent diplopia over 2 months. A 29 mm of maximum intracranial diameter (ICD) VS with secondary obstructive hydrocephalus was diagnosed. The patient underwent a ventriculo-peritoneal shunt with resolution of her symptoms and opted for initial WWR management. Interval scanning between 2007 and 2014 showed progressive reduction in the maximum ICD together with reduction in the degree of central tumor enhancement. Maximum ICD at most recent follow up was 22 mm. A 28-year-old female was referred with right sensorineural deafness. A right VS of maximum ICD of 27 mm was diagnosed. Initial WWR management was planned after discussion. Serial imaging showed an initial increase in the size of the tumor followed by progressive reduction in size. The most recent follow up showed a maximum ICD of 20 mm. Conclusion: Early WWR management can be associated with spontaneous shrinkage of VS over time. Prospective clinical study of larger numbers of such cases using the UK VS database may help to identify predictive factors for the spontaneous regression of VS. PMID:27280055

  5. Etiology of primary spontaneous pneumothorax.

    PubMed

    Lyra, Roberto de Menezes

    2016-01-01

    With the advent of HRCT, primary spontaneous pneumothorax has come to be better understood and managed, because its etiology can now be identified in most cases. Primary spontaneous pneumothorax is mainly caused by the rupture of a small subpleural emphysematous vesicle (designated a bleb) or of a subpleural paraseptal emphysematous lesion (designated a bulla). The aim of this pictorial essay was to improve the understanding of primary spontaneous pneumothorax and to propose a description of the major anatomical lesions found during surgery. RESUMO Com o advento da TCAR, o pneumotórax espontâneo primário passou a ser mais bem entendido e conduzido, pois sua etiologia pode ser atualmente identificada na maioria dos casos. O pneumotórax espontâneo primário tem como principal causa a rotura de uma pequena vesícula enfisematosa subpleural, denominada bleb ou de uma lesão enfisematosa parasseptal subpleural, denominada bulla. O objetivo deste ensaio pictórico foi melhorar o entendimento do pneumotórax espontâneo primário e propor uma descrição das principais lesões anatômicas encontradas durante a cirurgia. PMID:27383937

  6. Spontaneous osteoblastic osteosarcoma in a Mongolian gerbil (Meriones unguiculatus).

    PubMed

    Salyards, Gregory W; Blas-Machado, Uriel; Mishra, Sasmita; Harvey, Stephen B; Butler, Abigail M

    2013-02-01

    Spontaneous neoplasms in Mongolian gerbils have an incidence of 20% to 26.8%, but osteosarcomas occur at a much lower rate. Here we report a 1-y-old Mongolian gerbil with a spontaneous osteosarcoma at the level of the proximal tibia, with metastases to the pectoral muscles and lungs. Grossly, the tibial mass obliterated the tibia and adjacent muscles, and an axillary mass with a bloody, cavitary center expanded the pectoral muscles. Microscopically, the tibial mass was an infiltrative, osteoblastic mesenchymal neoplasm, and the axillary mass was an anaplastic mesenchymal neoplasm with hemorrhage. The lung contained multiple metastatic foci. Immunohistochemistry for osteonectin was strongly positive in the tibial, axillary, and pulmonary metastases. Although osteosarcoma is the most common primary malignant bone neoplasm that occurs spontaneously in all laboratory and domestic animal species and humans, it arises less frequently than does other neoplasms. The current case of spontaneous osteoblastic osteosarcoma of the proximal tibia and metastases to the pectoral muscles and lung in a Mongolian gerbil is similar in presentation, histology, and predilection site of both osteoblastic and telangiectatic osteosarcomas in humans. In addition, this case is an unusual manifestation of osteosarcoma in the appendicular skeleton of a Mongolian gerbil. PMID:23561939

  7. Sounds elicit relative left frontal alpha activity in 2-month-old infants

    PubMed Central

    Mai, Xiaoqin; Xu, Lin; Li, Mingyan; Shao, Jie; Zhao, Zhengyan; Lamm, Connie; Fox, Nathan A.; Nelson, Charles A.; Lozoff, Betsy

    2015-01-01

    As one kind of sounds, human voices are important for language acquisition and human-infant relations. Human voices have positive effects on infants, e.g., soothe infants and evoke an infant's smile. Increased left relative to right frontal alpha activity as assessed by the electroencephalogram (EEG) is considered to reflect approach-related emotions. In the present study, we recorded the EEG in thirty-eight 2-month-old infants during a baseline period and then while they listened to sounds, i.e., human voices. Infants displayed increased relative left frontal alpha activity in response to sounds compared to the baseline condition. These results suggest that sounds can elicit relative left frontal activity in young infants, and that this approach-related emotion presents early in life. PMID:25242501

  8. Hybrid Approach for Automatic Evaluation of Emotion Elicitation Oriented to People with Intellectual Disabilities

    NASA Astrophysics Data System (ADS)

    Martínez, R.; de Ipiña, K. López; Irigoyen, E.; Asla, N.

    People with intellectual disabilities and elderly need physical and intellectual support to ensuring independent living. This is one of the main issues in applying Information and Communication Technology (ICT) into Assistive Technology field. In this sense the development of appropriated Intelligent Systems (ISs) offers new perspectives to this community. In our project a new IS system (LAGUNTXO) which adds user affective information oriented to people with intellectual disabilities has been developed. The system integrates a Human Emotion Analysis System (HEAS) which attempts to solve critical situations for this community as block stages. In the development of the HEAS one of the critical issues was to create appropriated databases to train the system due to the difficulty to simulate pre-block stages in laboratory. Finally a films and real sequences based emotion elicitation database was created. The elicitation material was categorized with more actual features based on discrete emotions and dimensional terms (pleasant, unpleasant). Classically the evaluation is carried out by a specialist (psychologist). In this work we present a hybrid approach for Automatic Evaluation of Emotion Elicitation databases based on Machine Learning classifiers and K-means clustering. The new categorization and the automatic evaluation show a high level of accuracy with respect to others methodologies presented in the literature.

  9. Expert elicitation on the uncertainties associated with chronic wasting disease.

    PubMed

    Tyshenko, Michael G; Oraby, Tamer; Darshan, Shalu; Westphal, Margit; Croteau, Maxine C; Aspinall, Willy; Elsaadany, Susie; Krewski, Daniel; Cashman, Neil

    2016-01-01

    A high degree of uncertainty exists for chronic wasting disease (CWD) transmission factors in farmed and wild cervids. Evaluating the factors is important as it helps to inform future risk management strategies. Expert opinion is often used to assist decision making in a number of health, science, and technology domains where data may be sparse or missing. Using the "Classical Model" of elicitation, a group of experts was asked to estimate the most likely values for several risk factors affecting CWD transmission. The formalized expert elicitation helped structure the issues and hence provide a rational basis for estimating some transmission risk factors for which evidence is lacking. Considered judgments regarding environmental transmission, latency of CWD transmission, management, and species barrier were provided by the experts. Uncertainties for many items were determined to be large, highlighting areas requiring more research. The elicited values may be used as surrogate values until research evidence becomes available. PMID:27556566

  10. Expert elicitation on the uncertainties associated with chronic wasting disease.

    PubMed

    Tyshenko, Michael G; Oraby, Tamer; Darshan, Shalu; Westphal, Margit; Croteau, Maxine C; Aspinall, Willy; Elsaadany, Susie; Krewski, Daniel; Cashman, Neil

    2016-01-01

    A high degree of uncertainty exists for chronic wasting disease (CWD) transmission factors in farmed and wild cervids. Evaluating the factors is important as it helps to inform future risk management strategies. Expert opinion is often used to assist decision making in a number of health, science, and technology domains where data may be sparse or missing. Using the "Classical Model" of elicitation, a group of experts was asked to estimate the most likely values for several risk factors affecting CWD transmission. The formalized expert elicitation helped structure the issues and hence provide a rational basis for estimating some transmission risk factors for which evidence is lacking. Considered judgments regarding environmental transmission, latency of CWD transmission, management, and species barrier were provided by the experts. Uncertainties for many items were determined to be large, highlighting areas requiring more research. The elicited values may be used as surrogate values until research evidence becomes available.

  11. Spontaneous mutagenesis: experimental, genetic and other factors.

    PubMed

    Smith, K C

    1992-08-01

    Spontaneous mutations are "the net result of all that can go wrong with DNA during the life cycle of an organism" (Glickman et al., 1986). Thus, the types and amounts of spontaneous mutations produced are the resultant of all the cellular processes that are mutagenic and those that are antimutagenic. It is not widely appreciated that the types and frequencies of spontaneous mutations change markedly with subtle changes in experimental conditions. All types of mutations are produced spontaneously, i.e., base substitutions, frameshifts, insertions and deletions. However, very few papers have appeared that are devoted exclusively to the study of the mechanisms of spontaneous mutagenesis, and of the subtle experimental factors that affect the types and frequencies of spontaneous mutations. This is unfortunate because spontaneous mutagenesis appears to play a major role in evolution, aging, and carcinogenesis. This review emphasizes subtle experimental variables that markedly affect the results of a spontaneous mutation experiment. A thorough understanding of these variables eliminates the need for a theory of "directed" mutagenesis. The intrinsic instability of DNA, and the types of normal metabolic lesions that are produced in DNA that lead to mutations via errors made in replication, repair, and recombination are reviewed, as is the genetic control of spontaneous mutagenesis. As with spontaneous mutagenesis, spontaneous carcinogenesis can also be considered to be the net result of all that can go wrong with DNA during the life of an organism. PMID:1378531

  12. Biologically inspired robots elicit a robust fear response in zebrafish

    NASA Astrophysics Data System (ADS)

    Ladu, Fabrizio; Bartolini, Tiziana; Panitz, Sarah G.; Butail, Sachit; Macrı, Simone; Porfiri, Maurizio

    2015-03-01

    We investigate the behavioral response of zebrafish to three fear-evoking stimuli. In a binary choice test, zebrafish are exposed to a live allopatric predator, a biologically-inspired robot, and a computer-animated image of the live predator. A target tracking algorithm is developed to score zebrafish behavior. Unlike computer-animated images, the robotic and live predator elicit a robust avoidance response. Importantly, the robotic stimulus elicits more consistent inter-individual responses than the live predator. Results from this effort are expected to aid in hypothesis-driven studies on zebrafish fear response, by offering a valuable approach to maximize data-throughput and minimize animal subjects.

  13. Evidence that potential fish predators elicit the production of carapace vibrations by the American lobster.

    PubMed

    Ward, Daniel; Morison, Françoise; Morrissey, Elizabeth; Jenks, Kyle; Watson, Winsor H

    2011-08-01

    American lobsters (Homarus americanus) will on rare occasions produce sounds by vibrating their dorsal carapace. Although this behavior can be elicited in the laboratory by handling lobsters, the stimulus that triggers the production of sounds in the lobster's natural habitat is not known. We investigated the influence of two fish that are known to prey on lobsters, cod (Gadus morhua) and striped bass (Morone saxatilis), on the production of sounds by American lobsters. In addition, we examined the response of the same fish to the sounds the lobsters produced. Although solitary lobsters spontaneously produced sounds at a low rate of 1.2 ± 0.23 sound events per 30 min, the presence of a single cod or striped bass led to an increase in the rate of sound production (cod: 51.1 ± 13.1 events per 30 min; striped bass: 17.0 ± 7.0 events per 30 min). Most (74.6 ± 6.6%) of the 292 sound events recorded occurred when a fish came within 0.5 m of a lobster, but a fish did not have to come into contact with a lobster to elicit sounds. Immediately following the production of a sound by a lobster, fish turned and swam away significantly faster than when they encountered a lobster that did not make a sound. Moreover, after striped bass (but not cod) experienced a number of these sound events, they subsequently tended to avoid swimming close to the lobsters. These data, taken together, suggest that sound production by American lobsters may serve to deter potential fish predators. PMID:21753058

  14. Evidence that potential fish predators elicit the production of carapace vibrations by the American lobster.

    PubMed

    Ward, Daniel; Morison, Françoise; Morrissey, Elizabeth; Jenks, Kyle; Watson, Winsor H

    2011-08-01

    American lobsters (Homarus americanus) will on rare occasions produce sounds by vibrating their dorsal carapace. Although this behavior can be elicited in the laboratory by handling lobsters, the stimulus that triggers the production of sounds in the lobster's natural habitat is not known. We investigated the influence of two fish that are known to prey on lobsters, cod (Gadus morhua) and striped bass (Morone saxatilis), on the production of sounds by American lobsters. In addition, we examined the response of the same fish to the sounds the lobsters produced. Although solitary lobsters spontaneously produced sounds at a low rate of 1.2 ± 0.23 sound events per 30 min, the presence of a single cod or striped bass led to an increase in the rate of sound production (cod: 51.1 ± 13.1 events per 30 min; striped bass: 17.0 ± 7.0 events per 30 min). Most (74.6 ± 6.6%) of the 292 sound events recorded occurred when a fish came within 0.5 m of a lobster, but a fish did not have to come into contact with a lobster to elicit sounds. Immediately following the production of a sound by a lobster, fish turned and swam away significantly faster than when they encountered a lobster that did not make a sound. Moreover, after striped bass (but not cod) experienced a number of these sound events, they subsequently tended to avoid swimming close to the lobsters. These data, taken together, suggest that sound production by American lobsters may serve to deter potential fish predators.

  15. Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques.

    PubMed

    Zurawski, Gerard; Zurawski, Sandra; Flamar, Anne-Laure; Richert, Laura; Wagner, Ralf; Tomaras, Georgia D; Montefiori, David C; Roederer, Mario; Ferrari, Guido; Lacabaratz, Christine; Bonnabau, Henri; Klucar, Peter; Wang, Zhiqing; Foulds, Kathryn E; Kao, Shing-Fen; Yates, Nicole L; LaBranche, Celia; Jacobs, Bertram L; Kibler, Karen; Asbach, Benedikt; Kliche, Alexander; Salazar, Andres; Reed, Steve; Self, Steve; Gottardo, Raphael; Galmin, Lindsey; Weiss, Deborah; Cristillo, Anthony; Thiebaut, Rodolphe; Pantaleo, Giuseppe; Levy, Yves

    2016-01-01

    Improved antigenicity against HIV-1 envelope (Env) protein is needed to elicit vaccine-induced protective immunity in humans. Here we describe the first tests in non-human primates (NHPs) of Env gp140 protein fused to a humanized anti-LOX-1 recombinant antibody for delivering Env directly to LOX-1-bearing antigen presenting cells, especially dendritic cells (DC). LOX-1, or 1ectin-like oxidized low-density lipoprotein (LDL) receptor-1, is expressed on various antigen presenting cells and endothelial cells, and is involved in promoting humoral immune responses. The anti-LOX-1 Env gp140 fusion protein was tested for priming immune responses and boosting responses in animals primed with replication competent NYVAC-KC Env gp140 vaccinia virus. Anti-LOX-1 Env gp140 vaccination elicited robust cellular and humoral responses when used for either priming or boosting immunity. Co-administration with Poly ICLC, a TLR3 agonist, was superior to GLA, a TLR4 agonist. Both CD4+ and CD8+ Env-specific T cell responses were elicited by anti-LOX-1 Env gp140, but in particular the CD4+ T cells were multifunctional and directed to multiple epitopes. Serum IgG and IgA antibody responses induced by anti-LOX-1 Env gp140 against various gp140 domains were cross-reactive across HIV-1 clades; however, the sera neutralized only HIV-1 bearing sequences most similar to the clade C 96ZM651 Env gp140 carried by the anti-LOX-1 vehicle. These data, as well as the safety of this protein vaccine, justify further exploration of this DC-targeting vaccine approach for protective immunity against HIV-1. PMID:27077384

  16. Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques

    PubMed Central

    Zurawski, Sandra; Flamar, Anne-Laure; Richert, Laura; Wagner, Ralf; Tomaras, Georgia D.; Montefiori, David C.; Roederer, Mario; Ferrari, Guido; Lacabaratz, Christine; Bonnabau, Henri; Klucar, Peter; Wang, Zhiqing; Foulds, Kathryn E.; Kao, Shing-Fen; Yates, Nicole L.; LaBranche, Celia; Jacobs, Bertram L.; Kibler, Karen; Asbach, Benedikt; Kliche, Alexander; Salazar, Andres; Reed, Steve; Self, Steve; Gottardo, Raphael; Galmin, Lindsey; Weiss, Deborah; Cristillo, Anthony; Thiebaut, Rodolphe; Pantaleo, Giuseppe; Levy, Yves

    2016-01-01

    Improved antigenicity against HIV-1 envelope (Env) protein is needed to elicit vaccine-induced protective immunity in humans. Here we describe the first tests in non-human primates (NHPs) of Env gp140 protein fused to a humanized anti-LOX-1 recombinant antibody for delivering Env directly to LOX-1-bearing antigen presenting cells, especially dendritic cells (DC). LOX-1, or 1ectin-like oxidized low-density lipoprotein (LDL) receptor-1, is expressed on various antigen presenting cells and endothelial cells, and is involved in promoting humoral immune responses. The anti-LOX-1 Env gp140 fusion protein was tested for priming immune responses and boosting responses in animals primed with replication competent NYVAC-KC Env gp140 vaccinia virus. Anti-LOX-1 Env gp140 vaccination elicited robust cellular and humoral responses when used for either priming or boosting immunity. Co-administration with Poly ICLC, a TLR3 agonist, was superior to GLA, a TLR4 agonist. Both CD4+ and CD8+ Env-specific T cell responses were elicited by anti-LOX-1 Env gp140, but in particular the CD4+ T cells were multifunctional and directed to multiple epitopes. Serum IgG and IgA antibody responses induced by anti-LOX-1 Env gp140 against various gp140 domains were cross-reactive across HIV-1 clades; however, the sera neutralized only HIV-1 bearing sequences most similar to the clade C 96ZM651 Env gp140 carried by the anti-LOX-1 vehicle. These data, as well as the safety of this protein vaccine, justify further exploration of this DC-targeting vaccine approach for protective immunity against HIV-1. PMID:27077384

  17. Rhesus Monkeys ("Macaca Mulatta") Spontaneously Compute Addition Operations Over Large Numbers

    ERIC Educational Resources Information Center

    Flombaum, Jonathan I.; Junge, Justin A.; Hauser, Marc D.

    2005-01-01

    Mathematics is a uniquely human capacity. Studies of animals and human infants reveal, however, that this capacity builds on language-independent mechanisms for quantifying small numbers ([less than] 4) precisely and large numbers approximately. It is unclear whether animals and human infants can spontaneously tap mechanisms for quantifying large…

  18. Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides.

    PubMed

    Scallan, Joshua P; Davis, Michael J; Huxley, Virginia H

    2013-10-15

    Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones released into the bloodstream in response to hypervolaemia or fluid shifts to the central circulation. The actions of both peptides include natriuresis and diuresis, a decrease in systemic blood pressure, and inhibition of the renin-angiotensin-aldosterone system. Further, ANP and BNP elicit increases in blood microvessel permeability sufficient to cause protein and fluid extravasation into the interstitium to reduce the vascular volume. Given the importance of the lymphatic vasculature in maintaining fluid balance, we tested the hypothesis that ANP or BNP (100 nM) would likewise elevate lymphatic permeability (Ps) to serum albumin. Using a microfluorometric technique adapted to in vivo lymphatic vessels, we determined that rat mesenteric collecting lymphatic Ps to rat serum albumin increased by 2.0 ± 0.4-fold (P = 0.01, n = 7) and 2.7 ± 0.8-fold (P = 0.07, n = 7) with ANP and BNP, respectively. In addition to measuring Ps responses, we observed changes in spontaneous contraction amplitude and frequency from the albumin flux tracings in vivo. Notably, ANP abolished spontaneous contraction amplitude (P = 0.005) and frequency (P = 0.006), while BNP augmented both parameters by ∼2-fold (P < 0.01 each). These effects of ANP and BNP on contractile function were examined further by using an in vitro assay. In aggregate, these data support the theory that an increase in collecting lymphatic permeability opposes the absorptive function of the lymphatic capillaries, and aids in the retention of protein and fluid in the interstitial space to counteract volume expansion.

  19. The (perceived) meaning of spontaneous thoughts.

    PubMed

    Morewedge, Carey K; Giblin, Colleen E; Norton, Michael I

    2014-08-01

    Spontaneous thoughts, the output of a broad category of uncontrolled and inaccessible higher order mental processes, arise frequently in everyday life. The seeming randomness by which spontaneous thoughts arise might give people good reason to dismiss them as meaningless. We suggest that it is precisely the lack of control over and access to the processes by which they arise that leads people to perceive spontaneous thoughts as revealing meaningful self-insight. Consequently, spontaneous thoughts potently influence judgment. A series of experiments provides evidence supporting two hypotheses. First, we hypothesize that the more a thought is perceived to be spontaneous, the more it is perceived to provide meaningful self-insight. Participants perceived more spontaneous kinds of thought (e.g., intuition) to reveal greater self-insight than did more controlled kinds of thought in Study 1 (e.g., deliberation). In Studies 2 and 3, participants perceived thoughts with the same content and target to reveal greater self-insight when spontaneously rather than deliberately generated (i.e., childhood memories and impressions formed). Second, we hypothesize that the greater self-insight attributed to thoughts that are (perceived to be) spontaneous leads those thoughts to more potently influence judgment. Participants felt more sexually attracted to an attractive person whom they thought of spontaneously than deliberately in Study 4, and reported their commitment to a current romantic relationship would be more affected by the spontaneous rather than deliberate recollection of a good or bad experience with their romantic partner in Study 5. PMID:24820251

  20. The (perceived) meaning of spontaneous thoughts.

    PubMed

    Morewedge, Carey K; Giblin, Colleen E; Norton, Michael I

    2014-08-01

    Spontaneous thoughts, the output of a broad category of uncontrolled and inaccessible higher order mental processes, arise frequently in everyday life. The seeming randomness by which spontaneous thoughts arise might give people good reason to dismiss them as meaningless. We suggest that it is precisely the lack of control over and access to the processes by which they arise that leads people to perceive spontaneous thoughts as revealing meaningful self-insight. Consequently, spontaneous thoughts potently influence judgment. A series of experiments provides evidence supporting two hypotheses. First, we hypothesize that the more a thought is perceived to be spontaneous, the more it is perceived to provide meaningful self-insight. Participants perceived more spontaneous kinds of thought (e.g., intuition) to reveal greater self-insight than did more controlled kinds of thought in Study 1 (e.g., deliberation). In Studies 2 and 3, participants perceived thoughts with the same content and target to reveal greater self-insight when spontaneously rather than deliberately generated (i.e., childhood memories and impressions formed). Second, we hypothesize that the greater self-insight attributed to thoughts that are (perceived to be) spontaneous leads those thoughts to more potently influence judgment. Participants felt more sexually attracted to an attractive person whom they thought of spontaneously than deliberately in Study 4, and reported their commitment to a current romantic relationship would be more affected by the spontaneous rather than deliberate recollection of a good or bad experience with their romantic partner in Study 5.

  1. Moving beyond standard procedures to assess spontaneous recognition memory.

    PubMed

    Ameen-Ali, K E; Easton, A; Eacott, M J

    2015-06-01

    This review will consider how spontaneous tasks have been applied alongside neuroscientific techniques to test complex forms of recognition memory for objects and their environmental features, e.g. the spatial location of an object or the context in which it is presented. We discuss studies that investigate the roles of the perirhinal cortex and the hippocampus in recognition memory using standard testing paradigms, and consider how these findings contribute to the ongoing debate about whether recognition memory is a single unitary process or multiple processes that can be dissociated anatomically and functionally. Due to the wide use of spontaneous tasks, the need for improved procedures that reduce animal use is acknowledged, with multiple trial paradigms discussed as a novel way of reducing variability and animal numbers in these tasks. The importance of improving translation of animal models to humans is highlighted, with emphasis on a shift away from relying on the phenomenological experience of human subjects.

  2. Spontaneous colonic adenocarcinoma in marmosets.

    PubMed

    Lushbaugh, C C; Humason, G L; Swartzendruber, D C; Richter, C B; Gengozian, N

    1978-01-01

    We find that colonic adenocarcinoma, which is an extremely rare neoplasm of all animals except man and carcinogen-treated rodents, occurs spontaneously in some marmosets. The cotton-topped Saguinus oedipus oedipus is particularly prone to develop it, but we have found it also at necropsy in Callimico goeldii (Goeldi's marmoset). Numerous metastases to regional lymph nodes develop. The cancers arise de novo in the mucosa and early invade the submucosa and lymphatic apparatus and paracolonic lymph nodes. These findings and the continuing occurrence of this cancer in our colony suggests that the marmoset may be the long-sought primate model for experimental intestinal carcinogenesis.

  3. Skin scarification with Plasmodium falciparum peptide vaccine using synthetic TLR agonists as adjuvants elicits malaria sporozoite neutralizing immunity

    PubMed Central

    Mitchell, Robert A.; Altszuler, Rita; Frevert, Ute; Nardin, Elizabeth H.

    2016-01-01

    Malaria eradication will require a combination of vector control, chemotherapy and an easily administered vaccine. Sterile immunity can be elicited in humans by immunization with sporozoites, the infective stage injected by bite of the mosquito vector, however, whole parasite vaccines present formidable logistical challenges for production, storage and administration. The “gold standard” for infectious disease eradiation, the Smallpox Eradication Programme, utilized mass immunization using the skin scarification (SS) route. SS may more closely mimic the natural route of malaria infection initiated by sporozoites injected by mosquito bite which elicits both neutralizing antibodies and protective cell mediated immunity. We investigated the potential of SS immunization using a malaria repeat peptide containing a protective B cell epitope of Plasmodium falciparum, the most lethal human species, and delivery vehicles containing TLR agonists as adjuvants. In a murine model, SS immunization with peptide in combination with TLR-7/8 and -9 agonists elicited high levels of systemic sporozoite neutralizing antibody, Th1- type CD4+ T cells and resistance to challenge by bites of infected mosquitoes. SS provides the potential to elicit humoral immunity to target Plasmodium at multiple stages of its complex life cycle. PMID:27624667

  4. Skin scarification with Plasmodium falciparum peptide vaccine using synthetic TLR agonists as adjuvants elicits malaria sporozoite neutralizing immunity.

    PubMed

    Mitchell, Robert A; Altszuler, Rita; Frevert, Ute; Nardin, Elizabeth H

    2016-01-01

    Malaria eradication will require a combination of vector control, chemotherapy and an easily administered vaccine. Sterile immunity can be elicited in humans by immunization with sporozoites, the infective stage injected by bite of the mosquito vector, however, whole parasite vaccines present formidable logistical challenges for production, storage and administration. The "gold standard" for infectious disease eradiation, the Smallpox Eradication Programme, utilized mass immunization using the skin scarification (SS) route. SS may more closely mimic the natural route of malaria infection initiated by sporozoites injected by mosquito bite which elicits both neutralizing antibodies and protective cell mediated immunity. We investigated the potential of SS immunization using a malaria repeat peptide containing a protective B cell epitope of Plasmodium falciparum, the most lethal human species, and delivery vehicles containing TLR agonists as adjuvants. In a murine model, SS immunization with peptide in combination with TLR-7/8 and -9 agonists elicited high levels of systemic sporozoite neutralizing antibody, Th1- type CD4+ T cells and resistance to challenge by bites of infected mosquitoes. SS provides the potential to elicit humoral immunity to target Plasmodium at multiple stages of its complex life cycle. PMID:27624667

  5. Clinicians as Communication Partners: Developing a Mediated Discourse Elicitation Protocol

    ERIC Educational Resources Information Center

    Hengst, Julie A.; Duff, Melissa C.

    2007-01-01

    This article presents the development and piloting of a mediated discourse elicitation protocol. Grounded in situated theories of communication and informed by mediated discourse analysis, this protocol selectively samples familiar discourse types in a manner designed to preserve interactional aspects of communication. Critically, the mediated…

  6. Eliciting Students' Beliefs about Who Is Good at Mathematics

    ERIC Educational Resources Information Center

    Morge, Shelby P.

    2007-01-01

    This article highlights a series of activities designed to elicit students' mathematics-related beliefs, particularly those related to gender. As a result of the activities, females in upper-level classes rated themselves as having less confidence than males, and viewing a movie clip was sufficient for some students to modify their descriptions of…

  7. Modification of commercially available simulators to elicit decision making behavior.

    PubMed

    Salud, Jonathan; Ononye, Chiagozie; Salud, Lawrence; Pugh, Carla

    2012-01-01

    In recent years, simulation training has emerged as an innovative method for decreasing error and teaching complex procedures. Simulation has also been a valuable tool for evaluating investigatory and analytic thinking. By adding a specific, clinically oriented modification to a commercially available simulator, we were able to elicit first-year emergency medicine resident perceptions, actions, and decisions.

  8. Eliciting Design Patterns for E-Learning Systems

    ERIC Educational Resources Information Center

    Retalis, Symeon; Georgiakakis, Petros; Dimitriadis, Yannis

    2006-01-01

    Design pattern creation, especially in the e-learning domain, is a highly complex process that has not been sufficiently studied and formalized. In this paper, we propose a systematic pattern development cycle, whose most important aspects focus on reverse engineering of existing systems in order to elicit features that are cross-validated through…

  9. Eliciting Production of L2 Target Structures through Priming Activities

    ERIC Educational Resources Information Center

    McDonough, Kim; Trofimovich, Pavel; Neumann, Heike

    2015-01-01

    This study focuses on the pedagogical applications of structural priming research in an English for academic purposes (EAP) context, investigating whether priming activities are an effective tool for eliciting production of target grammatical structures. University students across four EAP classes carried out a total of 6 information-exchange…

  10. Computational Support for Early Elicitation and Classification of Tone

    ERIC Educational Resources Information Center

    Bird, Steven; Lee, Haejoong

    2014-01-01

    Investigating a tone language involves careful transcription of tone on words and phrases. This is challenging when the phonological categories--the tones or melodies--have not been identified. Effects such as coarticulation, sandhi, and phrase-level prosody appear as obstacles to early elicitation and classification of tone. This article presents…

  11. Photo-Elicitation: Reflexivity on Method, Analysis, and Graphic Portraits

    ERIC Educational Resources Information Center

    Richard, Veronica M.; Lahman, Maria K. E.

    2015-01-01

    In this methodological discussion, the authors detail and reflect on the processes of using photo-elicitation interviewing as a way to align with positive qualitative methodologies, to gain access to participant beliefs and values, and to highlight participant voices through their choices of words and visuals. A review of the literature and an…

  12. Engaging Young Children in Research through Photo Elicitation

    ERIC Educational Resources Information Center

    Pyle, Angela

    2013-01-01

    Embracing the new sociology of childhood, this paper describes a participatory research method built on a belief in the competency of young children. The paper begins with a critical review of the photo elicitation literature exploring the varied levels of children's participation. Drawing on the strengths of the previous research, a…

  13. Creating a Framework: Art Therapy Elicits the Narrative

    ERIC Educational Resources Information Center

    Harber, Karen

    2011-01-01

    A case study illustrates how art therapy was used to elicit the narrative of an adolescent male student in transition from incarceration to a transfer school setting. Childhood trauma was addressed in individual sessions and within a literacy group co-led by a reading specialist. The art therapist responded to the client's needs by broadening the…

  14. Stimulus Duration Preference at Electrode Sites Yielding Elicited Behavior

    NASA Technical Reports Server (NTRS)

    Cox, V. C.

    1970-01-01

    The latency to display eating or drinking during hypothalamic stimulation was compared with the preferred duration of the same stimulus intensity in a self-stimulation situation. All the animals preferred longer stimulus durations than those required to elicit eating or drinking

  15. The Role of Elicited Verbal Imitation in Toddlers' Word Learning

    ERIC Educational Resources Information Center

    Hodges, Rosemary; Munro, Natalie; Baker, Elise; McGregor, Karla; Docking, Kimberley; Arciuli, Joanne

    2016-01-01

    This study is about the role of elicited verbal imitation in toddler word learning. Forty-eight toddlers were taught eight nonwords linked to referents. During training, they were asked to imitate the nonwords. Naming of the referents was tested at three intervals (one minute later [uncued], five minutes, and 1-7 days later [cued]) and recognition…

  16. A Study of the Affective Responses Elicited by Occupational Stimuli

    ERIC Educational Resources Information Center

    Schoon, Craig G.

    1976-01-01

    The semantic differential was used to assess the properties of affect elicited by occupational stimuli. Vocationally committed men studying medicine, business, and engineering responded to a semantic differential containing occupational concepts. Results show a semantic space for all three groups composed of three orthogonal dimensions of affect…

  17. Elicited Role-Play of Commands and Requests.

    ERIC Educational Resources Information Center

    Strage, Amy; And Others

    Children's ability to understand the implied messages in indirect speech was investigated using a role play elicitation task. Subjects were asked to complete story endings using puppets for several scenerios involving a mother and her four children. In each of the stories the mother gives an indirect directive which is supposed to get the children…

  18. Elicited Production of Relative Clauses in Children with Williams Syndrome

    ERIC Educational Resources Information Center

    Zukowski, Andrea

    2009-01-01

    Relative clauses have been implicated alternately as a strength and a weakness in the language of people with Williams Syndrome (WS). To clarify the facts, an elicited production test was administered to 10 people with WS (age 10-16 years), 10 typically developing children (age 4-7 years), and 12 typically developing adults. Nearly every WS…

  19. Using Automatic Speech Recognition Technology with Elicited Oral Response Testing

    ERIC Educational Resources Information Center

    Cox, Troy L.; Davies, Randall S.

    2012-01-01

    This study examined the use of automatic speech recognition (ASR) scored elicited oral response (EOR) tests to assess the speaking ability of English language learners. It also examined the relationship between ASR-scored EOR and other language proficiency measures and the ability of the ASR to rate speakers without bias to gender or native…

  20. Elicitation Support Requirements of Multi-Expertise Teams

    ERIC Educational Resources Information Center

    Bitter-Rijpkema, Marlies; Martens, Rob; Jochems, Wim

    2005-01-01

    Tools to support knowledge elicitation are used more and more in situations where employees or students collaborate using the computer. Studies indicate that differences exist between experts and novices regarding their methods of work and reasoning. However, the commonly preferred approach tends to deal with team members as a single system with…

  1. A Task that Elicits Reasoning: A Dual Analysis

    ERIC Educational Resources Information Center

    Yankelewitz, Dina; Mueller, Mary; Maher, Carolyn A.

    2010-01-01

    This paper reports on the forms of reasoning elicited as fourth grade students in a suburban district and sixth grade students in an urban district worked on similar tasks involving reasoning with the use of Cuisenaire rods. Analysis of the two data sets shows similarities in the reasoning used by both groups of students on specific tasks, and the…

  2. Teacher Burnout and Self-Efficacy in Eliciting Social Support.

    ERIC Educational Resources Information Center

    Brouwers, Andre; Evers, Will J. G.; Tomic, Welko

    This study examined the relationship between perceived lack of social support, perceived self-efficacy in eliciting support at the workplace, and the three successive burnout symptoms (emotional exhaustion, depersonalization, and personal accomplishment) in a sample of 277 Dutch secondary school teachers. The study hypothesized that teachers'…

  3. Preparing Beginning Teachers to Elicit and Interpret Students' Mathematical Thinking

    ERIC Educational Resources Information Center

    Sleep, Laurie; Boerst, Timothy A.

    2012-01-01

    This study investigated how teacher education assignments can be designed to support beginning teachers in learning to do the work of teaching. We examined beginners' formative assessment practices--in particular, their eliciting and interpreting of students' mathematical thinking--in the context of an elementary mathematics methods assignment,…

  4. Surface expression and rapid internalization of macrosialin (mouse CD68) on elicited mouse peritoneal macrophages.

    PubMed

    Kurushima, H; Ramprasad, M; Kondratenko, N; Foster, D M; Quehenberger, O; Steinberg, D

    2000-01-01

    Macrosialin, the mouse homolog of human CD68, is a heavily glycosylated transmembrane protein found almost exclusively in macrophages. Its function remains uncertain. It has a high affinity for oxidized low-density lipoprotein (LDL) in ligand blots and antibodies against the human homolog, CD68, inhibit the binding of oxidized LDL to a human monocyte-derived cell line (THP-1). However, there is still controversy as to whether macrosialin, found predominantly in late endosomes, is expressed at all on the plasma membrane. The present studies, done in thioglycollate-elicited peritoneal macrophages, confirm that macrosialin is predominantly intracellular but show clearly that 10-15% of it is expressed on the cell surface. Exchange with intracellular pools occurs at an extremely high rate. The results are compatible with a surface function, including internalization of bound ligands or adhesion to surfaces.

  5. Diphenyl diselenide elicits antidepressant-like activity in rats exposed to monosodium glutamate: A contribution of serotonin uptake and Na(+), K(+)-ATPase activity.

    PubMed

    Quines, Caroline B; Rosa, Suzan G; Velasquez, Daniela; Da Rocha, Juliana T; Neto, José S S; Nogueira, Cristina W

    2016-03-15

    Depression is a disorder with symptoms manifested at the psychological, behavioral and physiological levels. Monosodium glutamate (MSG) is the most widely used additive in the food industry; however, some adverse effects induced by this additive have been demonstrated in experimental animals and humans, including functional and behavioral alterations. The aim of this study was to investigate the possible antidepressant-like effect of diphenyl diselenide (PhSe)2, an organoselenium compound with pharmacological properties already documented, in the depressive-like behavior induced by MSG in rats. Male and female newborn Wistar rats were divided in control and MSG groups, which received, respectively, a daily subcutaneous injection of saline (0.9%) or MSG (4g/kg/day) from the 1st to 5th postnatal day. At 60th day of life, animals received (PhSe)2 (10mg/kg, intragastrically) 25min before spontaneous locomotor and forced swimming tests (FST). The cerebral cortices of rats were removed to determine [(3)H] serotonin (5-HT) uptake and Na(+), K(+)-ATPase activity. A single administration of (PhSe)2 was effective against locomotor hyperactivity caused by MSG in rats. (PhSe)2 treatment protected against the increase in the immobility time and a decrease in the latency for the first episode of immobility in the FST induced by MSG. Furthermore, (PhSe)2 reduced the [(3)H] 5-HT uptake and restored Na(+), K(+)-ATPase activity altered by MSG. In the present study a single administration of (PhSe)2 elicited an antidepressant-like effect and decrease the synaptosomal [(3)H] 5-HT uptake and an increase in the Na(+), K(+)-ATPase activity in MSG-treated rats.

  6. Spontaneous biliary peritonitis in children.

    PubMed

    Kohli, Supreethi; Singhal, Anu; Arora, Anita; Singhal, Sanjeev

    2013-01-01

    Pediatric Spontaneous Bile duct perforation is a rare clinical condition with only around 150 cases reported worldwide. Early management gives excellent prognosis but the condition often presents a diagnostic dilemma. Hepato-biliary Technetium-99m-iminodiacetic acid scintiscan is the diagnostic investigation of choice but its availability in third world countries is limited. We present two cases of spontaneous biliary peritonitis in children, which were diagnosed without scintiscanning. The first case was a one-and -a half-year-old child, who was diagnosed with biliary peritonitis without pneumoperitoneum by a combination of Ultrasound (USG), Contrast enhanced computed tomography (CECT), and Magnetic Resonance Imaging (MRI). The child underwent USG-guided drainage and subsequent cholecystectomy with hepatico-jejunostomy. The second child also had biliary peritonitis without pneumoperitoneum, which was initially suspected on USG. CECT revealed dilated gall bladder and fluid collection in sub-hepatic space and pelvis. Abdominal paracentesis revealed presence of bile. The child responded to conservative therapy. Both are doing well on two-year follow-up. In a patient with jaundice, biliary tract abnormalities and/or free fluid, either generalized or localized to peri-cholecystic/sub-hepatic space on USG/CT/MRI, in the absence of pneumoperitoneum, suggest a diagnosis of biliary perforation even in the absence of scintiscanning.

  7. Spontaneous Biliary Peritonitis in Children

    PubMed Central

    Kohli, Supreethi; Singhal, Anu; Arora, Anita; Singhal, Sanjeev

    2013-01-01

    Pediatric Spontaneous Bile duct perforation is a rare clinical condition with only around 150 cases reported worldwide. Early management gives excellent prognosis but the condition often presents a diagnostic dilemma. Hepato-biliary Technetium-99m-iminodiacetic acid scintiscan is the diagnostic investigation of choice but its availability in third world countries is limited. We present two cases of spontaneous biliary peritonitis in children, which were diagnosed without scintiscanning. The first case was a one-and -a half-year-old child, who was diagnosed with biliary peritonitis without pneumoperitoneum by a combination of Ultrasound (USG), Contrast enhanced computed tomography (CECT), and Magnetic Resonance Imaging (MRI). The child underwent USG-guided drainage and subsequent cholecystectomy with hepatico-jejunostomy. The second child also had biliary peritonitis without pneumoperitoneum, which was initially suspected on USG. CECT revealed dilated gall bladder and fluid collection in sub-hepatic space and pelvis. Abdominal paracentesis revealed presence of bile. The child responded to conservative therapy. Both are doing well on two-year follow-up. In a patient with jaundice, biliary tract abnormalities and/or free fluid, either generalized or localized to peri-cholecystic/sub-hepatic space on USG/CT/MRI, in the absence of pneumoperitoneum, suggest a diagnosis of biliary perforation even in the absence of scintiscanning. PMID:24083062

  8. A Case of Multiple Spontaneous Keloid Scars

    PubMed Central

    Jfri, Abdulhadi; Rajeh, Nawal; Karkashan, Eman

    2015-01-01

    Keloid scars result from an abnormal healing response to cutaneous injury or inflammation that extends beyond the borders of the original wound. Spontaneous keloid scars forming in the absence of any previous trauma or surgical procedure are rare. Certain syndromes have been associated with this phenomenon, and few reports have discussed the evidence of single spontaneous keloid scar, which raises the question whether they are really spontaneous. Here, we present a 27-year-old mentally retarded single female with orbital hypertelorism, broad nasal bridge, repaired cleft lip and high-arched palate who presented with progressive multiple spontaneous keloid scars in different parts of her body which were confirmed histologically by the presence of typical keloidal collagen. This report supports the fact that keloid scars can appear spontaneously and are possibly linked to a genetic factor. Furthermore, it describes a new presentation of spontaneous keloid scars in the form of multiple large lesions in different sites of the body. PMID:26351423

  9. Spontaneous Pneumocephalus Associated with Pneumosinus Dilatans

    PubMed Central

    Lee, Jung-Sup; Kwon, Jeong-Taik; Suk, Jong-Sik

    2010-01-01

    The majority of cases of pneumocephalus are secondary to trauma or medical intervention. Spontaneous, non-traumatic pneumocephalus is an uncommon condition. Most cases of spontaneous pneumocephalus require surgery. However, if there is no evidence of infection or cerebrospinal fluid leak, bed rest and follow-up imaging is an alternative treatment. Herein, we report a 31-year-old man with spontaneous pneumocephalus associated with pneumosinus dilatans. PMID:20539803

  10. Differential Specificity and Immunogenicity of Adenovirus Type 5 Neutralizing Antibodies Elicited by Natural Infection or Immunization▿

    PubMed Central

    Cheng, Cheng; Gall, Jason G. D.; Nason, Martha; King, C. Richter; Koup, Richard A.; Roederer, Mario; McElrath, M. Juliana; Morgan, Cecilia A.; Churchyard, Gavin; Baden, Lindsey R.; Duerr, Ann C.; Keefer, Michael C.; Graham, Barney S.; Nabel, Gary J.

    2010-01-01

    A recent clinical trial of a T-cell-based AIDS vaccine delivered with recombinant adenovirus type 5 (rAd5) vectors showed no efficacy in lowering viral load and was associated with increased risk of human immunodeficiency virus type 1 (HIV-1) infection. Preexisting immunity to Ad5 in humans could therefore affect both immunogenicity and vaccine efficacy. We hypothesized that vaccine-induced immunity is differentially affected, depending on whether subjects were exposed to Ad5 by natural infection or by vaccination. Serum samples from vaccine trial subjects receiving a DNA/rAd5 AIDS vaccine with or without prior immunity to Ad5 were examined for the specificity of their Ad5 neutralizing antibodies and their effect on HIV-1 immune responses. Here, we report that rAd5 neutralizing antibodies were directed to different components of the virion, depending on whether they were elicited by natural infection or vaccination in HIV vaccine trial subjects. Neutralizing antibodies elicited by natural infection were directed largely to the Ad5 fiber, while exposure to rAd5 through vaccination elicited antibodies primarily to capsid proteins other than fiber. Notably, preexisting immunity to Ad5 fiber from natural infection significantly reduced the CD4 and CD8 cell responses to HIV Gag after DNA/rAd5 vaccination. The specificity of Ad5 neutralizing antibodies therefore differs depending on the route of exposure, and natural Ad5 infection compromises Ad5 vaccine-induced immunity to weak immunogens, such as HIV-1 Gag. These results have implications for future AIDS vaccine trials and the design of next-generation gene-based vaccine vectors. PMID:19846512

  11. SPONTANEOUS COAL COMBUSTION; MECHANISMS AND PREDICTION.

    USGS Publications Warehouse

    Herring, James R.; Rich, Fredrick J.

    1983-01-01

    Spontaneous ignition and combustion of coal is a major problem to the coal mining, shipping, and use industries; unintentional combustion causes loss of the resource as well as jeopardy to life and property. The hazard to life is especially acute in the case of underground coal mine fires that start by spontaneous ignition. It is the intention of this research to examine previously suggested causes of spontaneous ignition, to consider new evidence, and to suggest an experimental approach to determine which of these suggested causes is relevant to western U. S. coal. This discussion focuses only on causes and mechanism of spontaneous ignition.

  12. Nonlinear Analyses of Elicited Modal, Raised, and Pressed Rabbit Phonation

    PubMed Central

    Awan, Shaheen N.; Novaleski, Carolyn K.; Rousseau, Bernard

    2014-01-01

    Objectives/Hypothesis The purpose of this study was to use nonlinear dynamic analysis methods such as phase space portraits and correlation dimension (D2) as well as descriptive spectrographic analyses to characterize acoustic signals produced during evoked rabbit phonation. Methods Seventeen New Zealand white breeder rabbits were used to perform the study. A Grass S-88 stimulator (SA Instrumentation, Encinitas, CA) and constant current isolation unit (Grass Telefactor, model PSIU6; West Warwick, RI) were used to provide electrical stimulation to laryngeal musculature, and transglottal airflow rate and stimulation current (mA) were manipulated to elicit modal, raised intensity, and pressed phonations. Central 1 second portions of the most stable portion of the acoustic waveform for modal, raised intensity, and pressed phonations were edited, and then analyzed via phase space portraits, Poincaré sections, and the estimation of the correlation dimension (D2). In an attempt to limit the effects of the highly variable and nonstationary characteristics of some of the signals being analyzed, D2 analysis was also performed on the most stable central 200 ms portion of the acoustic waveform. Descriptive analysis of each phonation was also conducted using sound spectrograms. Results Results showed that the complexity of phonation and the subsequent acoustic waveform is increased as transglottal airflow rate and degree of glottal adduction is manipulated in the evoked rabbit phonation model. In particular, phonatory complexity, as quantified via correlation dimension analyses and demonstrated via spectrographic characteristics, increases from “modal” (i.e., phonation elicited at just above the phonation threshold pressure) to raised intensity (phonation elicited by increasing transglottal airflow rate) to pressed (phonation elicited by increasing the stimulation current delivered to the larynx). Variations in a single dynamic dimension (airflow rate or adductory force

  13. Sensory-evoked and spontaneous gamma and spindle bursts in neonatal rat motor cortex.

    PubMed

    An, Shuming; Kilb, Werner; Luhmann, Heiko J

    2014-08-13

    Self-generated neuronal activity originating from subcortical regions drives early spontaneous motor activity, which is a hallmark of the developing sensorimotor system. However, the neural activity patterns and role of primary motor cortex (M1) in these early movements are still unknown. Combining voltage-sensitive dye imaging (VSDI) with simultaneous extracellular multielectrode recordings in postnatal day 3 (P3)-P5 rat primary somatosensory cortex (S1) and M1 in vivo, we observed that tactile forepaw stimulation induced spindle bursts in S1 and gamma and spindle bursts in M1. Approximately 40% of the spontaneous gamma and spindle bursts in M1 were driven by early motor activity, whereas 23.7% of the M1 bursts triggered forepaw movements. Approximately 35% of the M1 bursts were uncorrelated to movements and these bursts had significantly fewer spikes and shorter burst duration. Focal electrical stimulation of layer V neurons in M1 mimicking physiologically relevant 40 Hz gamma or 10 Hz spindle burst activity reliably elicited forepaw movements. We conclude that M1 is already involved in somatosensory information processing during early development. M1 is mainly activated by tactile stimuli triggered by preceding spontaneous movements, which reach M1 via S1. Only a fraction of M1 activity transients trigger motor responses directly. We suggest that both spontaneously occurring and sensory-evoked gamma and spindle bursts in M1 contribute to the maturation of corticospinal and sensorimotor networks required for the refinement of sensorimotor coordination.

  14. Spontaneous prospective-memory processing: Unexpected fluency experiences trigger erroneous intention executions.

    PubMed

    Rummel, Jan; Meiser, Thorsten

    2016-01-01

    Event-based prospective memory is the ability to remember to execute an intention when an environmental cue occurs. It has been argued that, due to their special meaning, these cues are discrepant from their environment and therefore are sometimes spontaneously noticed. In line with this assumption, the likelihood that an intention will be executed increases with increased cue-discrepancy. It is not yet clear, however, whether these improvements are due to facilitated spontaneous noticing rather than to an increase in the efficiency of controlled cue-processing. To further investigate the spontaneous nature of cue-discrepancy benefits, we presented participants with stimuli that were unrelated to the intention but discrepant from other stimuli. Therefore, we experimentally increased the processing fluency of some stimuli for participants currently holding an intention by using different priming procedures. We found that stimuli whose fluency was increased via spaced repeated stimulus presentation (Experiment 1) or via short pre-exposure (Experiment 2a to 3) elicited a tendency to fulfill the intention despite its actual inappropriateness. Findings were inconsistent as to whether cue-memory uncertainty fosters the reliance on cue discrepancy for intention retrieval (Experiments 2a and 3). Taken together, the present findings provide converging evidence for a spontaneous discrepancy-based prospective-memory process which works independent of controlled processes. PMID:26304843

  15. The critical protein interactions and structures that elicit growth deregulation in cancer and viral replication.

    PubMed

    Ou, Horng D; May, Andrew P; O'Shea, Clodagh C

    2011-01-01

    One of the greatest challenges in biomedicine is to define the critical targets and network interactions that are subverted to elicit growth deregulation in human cells. Understanding and developing rational treatments for cancer requires a definition of the key molecular targets and how they interact to elicit the complex growth deregulation phenotype. Viral proteins provide discerning and powerful probes to understand both how cells work and how they can be manipulated using a minimal number of components. The small DNA viruses have evolved to target inherent weaknesses in cellular protein interaction networks to hijack the cellular DNA and protein replication machinery. In the battle to escape the inevitability of senescence and programmed cell death, cancers have converged on similar mechanisms, through the acquisition and selection of somatic mutations that drive unchecked cellular replication in tumors. Understanding the dynamic mechanisms through which a minimal number of viral proteins promote host cells to undergo unscheduled and pathological replication is a powerful strategy to identify critical targets that are also disrupted in cancer. Viruses can therefore be used as tools to probe the system-wide protein-protein interactions and structures that drive growth deregulation in human cells. Ultimately this can provide a path for developing system context-dependent therapeutics. This review will describe ongoing experimental approaches using viruses to study pathways deregulated in cancer, with a particular focus on viral cellular protein-protein interactions and structures. PMID:21061422

  16. Whole Spontaneous Spinal Epidural Hematoma

    PubMed Central

    Yoon, Kyeong-Wook; Song, Jae Gyok; Ryu, Jae-Wook

    2014-01-01

    A 26-year-old male who had no underlying disease, including coagulopathy, underwent thoracotomy and bleeding control due to hemothorax. On the fifth postoperative day, paralysis of both lower limbs occurred. Urgent spine magnetic resonance imaging showed a massive anterior spinal epidural hematoma from C2 to L1 level with different signal intensities, which was suspected to be staged hemorrhage. Hematoma evacuation with decompressive laminectomy was performed. The patient's neurologic deterioration was recovered immediately, and he was discharged without neurological deficits. A drug history of naftazone, which could induce a drug-induced platelet dysfunction, was revealed retrospectively. To our knowledge, this is the first report of whole spontaneous spinal epidural hematoma in a young patient, with a history of hemorrhoid medication. PMID:24967052

  17. Fog spontaneously folds mosquito wings

    NASA Astrophysics Data System (ADS)

    Dickerson, Andrew K.; Liu, Xing; Zhu, Ting; Hu, David L.

    2015-02-01

    The flexibility of insect wings confers aerodynamic benefits, but can also present a hazard if exposed to fog or dew. Fog can cause water to accumulate on wings, bending them into tight taco shapes and rendering them useless for flight. In this combined experimental and theoretical study, we use high-speed video to film the spontaneous folding of isolated mosquito wings due to the evaporation of a water drop. We predict shapes of the deformed wing using two-dimensional elastica theory, considering both surface tension and Laplace pressure. We also recommend fold-resistant geometries for the wings of flapping micro-aerial vehicles. Our work reveals the mechanism of insect wing folding and provides a framework for further study of capillarity-driven folding in both natural and biomimetic systems at small scales.

  18. Spontaneous UC emission from SSTRa

    SciTech Connect

    Kutschera, W.; Ahmad, I.; Armato S.G. III; Friedman, A.M.; Gindler, J.E.; Henning, W.; Ishii, T.; Paul, M.; Rehm, K.E.

    1985-12-01

    The spontaneous emission of UC from SSTRa, recently discovered by Rose and Jones, has been confirmed, and the mass of the emitted particles unambiguously identified. The present measurement was performed with a SSXTh source containing 9.2 mCi of SSTRa. An Enge split-pole magnetic spectrograph was used to suppress the intense alpha radiation and to identify the UC particles. The spectrograph was calibrated with tandem-accelerated beams of UC, TC, and SC. In six days of decay counting, twenty-four UC events were observed yielding a branching ratio of (4.7 +- 1.3) x 10 for the emission of UC from SSTRa relative to that of alpha particles. The value is in fair agreement with the result of Rose and Jones, (8.5 +- 2.5) x 10 , and with more recent measurements from other laboratories.

  19. Detailed description of spontaneous emission

    NASA Astrophysics Data System (ADS)

    Guryev, M. V.

    2012-08-01

    The wave side of wave-photon duality, describing light as an electromagnetic field (EMF), is used in this article. The EMF of spontaneous light emission (SE) of a laser-excited atom is calculated from first principles for the first time. This calculation is done using the simple method of atomic quantum electrodynamics. The EMF of SE is also calculated for three types of polyatomic light sources excited by a laser. It is shown that light radiated by such sources can be coherent, which explains recent experiments on SE of laser-excited atoms. Small sources of SE can be superradiant, which also conforms to experiment. Thus, SE is shown not to be a random event itself. Random properties of natural light are simply explained as a result of thermal excitation randomness without additional hypotheses. The EMF of SE is described by simple complex functions, but not real ones.

  20. Spontaneous Pneumoperitoneum due to Constipation

    PubMed Central

    Yamana, Ippei; Noritomi, Tomoaki; Takeno, Shinsuke; Tatsuya, Hashimoto; Sato, Keisuke; Shimaoka, Hideki; Yamaguchi, Ryosuke; Ishii, Fumiaki; Yamada, Teppei; Yamashita, Yuichi

    2015-01-01

    We report a rare case of spontaneous pneumoperitoneum. An 82-year-old Japanese male patient was referred to our hospital because of constipation and abdominal pain. Abdominal computed tomography revealed a large amount of feces in the colon and rectum, and free air in the abdomen. Based on these findings, the patient was diagnosed with gastrointestinal perforation. Emergency exploratory laparotomy was performed. Neither perforation nor ischemic changes were recognized in the digestive tract. The patient's defecation was managed postoperatively until discharge on the 13th postoperative day. The authors assumed that free air, which was released after a mucosal injury due to the internal pressure caused by the presence of a large amount of feces in the colon and rectum, had penetrated the bowel wall through the bowel mucosa. We herein report the present case while also reviewing the pertinent literature. PMID:26676063

  1. Spontaneous Spinal Epidural Hematoma Report.

    PubMed

    Kukreja, Sunil; Nanda, Anil

    2016-01-01

    We report a case of spontaneous spinal epidural hematoma in a 12-year-old female, who presented with significant upper and lower extremities weakness preceded by pain around the neck and shoulder girdle. Magnetic resonance imaging revealed epidural hematoma extending from C6-T2 with characteristic heterogeneously hyperintensity on T2 and homogenously isointensity on T1. Emergent spinal decompression was performed. However, the patient remained substantially weak in her lower extremities and was wheelchair bound at 3 months postoperatively. We have discussed clinical features, predisposing events, pathogenesis and treatment guidelines described in the literature. We also aim to reinforce the notion of keeping a high degree of clinical suspicion to identify and intervene at the earliest stage to prevent the physically and socially challenging consequences of SSEH. PMID:27598898

  2. Spontaneous rupture on irregular faults

    NASA Astrophysics Data System (ADS)

    Liu, C.

    2014-12-01

    It is now know (e.g. Robinson et al., 2006) that when ruptures propagate around bends, the rupture velocity decrease. In the extreme case, a large bend in the fault can stop the rupture. We develop a 2-D finite difference method to simulate spontaneous dynamic rupture on irregular faults. This method is based on a second order leap-frog finite difference scheme on a uniform mesh of triangles. A relaxation method is used to generate an irregular fault geometry-conforming mesh from the uniform mesh. Through this numerical coordinate mapping, the elastic wave equations are transformed and solved in a curvilinear coordinate system. Extensive numerical experiments using the linear slip-weakening law will be shown to demonstrate the effect of fault geometry on rupture properties. A long term goal is to simulate the strong ground motion near the vicinity of bends, jogs, etc.

  3. Spontaneous adrenal haemorrhage in pregnancy

    PubMed Central

    A, Anagnostopoulos; S, Sharma

    2011-01-01

    The authors present a case of spontaneous adrenal haemorrhage, in a 28-year-old woman at 36 weeks of a twin pregnancy. Initial symptom was sudden onset chest pain which soon migrated to abdomen, accompanied by hypovolaemic shock and fetal bradycardia. Subsequent caesarean section for suspected placental abruption and resuscitation with nine units of blood, 10 of cryoprecipitate, four of fresh frozen plasma and two of platelets, in order to treat anaemia of Hgb of 3.6 g/dl and disseminated intravascular coagulation, failed to stabilise the woman. A CT scan of abdomen and pelvis then revealed a 15×17×17 cm retroperitoneal haematoma, secondary to right adrenal haemorrhage. Management was with laparotomy drainage and packing of the retroperitoneal haematoma along with the use of activated factor VII. Adrenal haemorrhage in pregnancy is an extremely rare, acute, life-threatening condition, presenting with non-specific symptoms. PMID:22679231

  4. Erythrocytosis in Spontaneously Hypertensive Rats

    PubMed Central

    Sen, Subha; Hoffman, George C.; Stowe, Nicholas T.; Smeby, Robert R.; Bumpus, F. Merlin

    1972-01-01

    During the study of an inbred strain of Wistar rats which spontaneously develop hypertension when they reach a weight of approximately 150 g, it was found that these animals also develop an erythrocytosis. A significant increase in red cell count was observed in spontaneously hypertensive (SH) rats (8-11 × 106 RBC/mm3) when compared with normotensive rats (6-7 × 106 RBC/mm3) of the same strain. This increase in red cell count paralleled the increase in body weight and the rise in blood pressure. Since the plasma volume, as measured with labeled albumin was normal, there was an absolute increase in red cells. The hematocrit and hemoglobin content of the blood measured in SH rats were only slightly greater than those found in normotensive rats. However, the mean cell volume (MCV) of the red cells in the SH rats was 45-47 μ3 as compared with 51-53 μ3 in normotensive rats. A fourfold increase in 24 hr 59Fe incorporation into the red cells was found in the SH rats when compared with normotensive controls. The bone marrow of the SH rats showed erythroid hyperplasia. When the SH rats were treated with α-methyldopa (Aldomet 200 mg/kg daily, i.p.) the red cell count fell in parallel with the drop in blood pressure. No change in red cell count or blood pressure was observed in normotensive rats treated in the same manner. The erythropoietin titer was high in SH rats, and was undetectable in normotensive rats. These observations suggest a direct relationship between the hypertension and the erythrocytosis mediated by erythropoietin; both are genetically controlled. PMID:5011107

  5. Spontaneous decidualization in pseudopregnant rats with vitamin E deficiency.

    PubMed

    Lang, Nan; Wu, Bin; He, Bin; Wang, Lili; Wang, Jiedong

    2016-05-13

    Successful implantation of an embryo requires adequate depth of invasion in the endometrium, which depends upon decidualization. The aim of the present study was to elucidate why humans experience spontaneous decidualization and menstruation while most other mammals do not. We established a spontaneous decidualization model in pseudopregnant rats with vitamin E deficiency (VED) to investigate mechanisms associated with spontaneous decidualization. Vaginal smears were used to monitor bleeding while vitamin E levels were analyzed with a commercial vitamin E assay kit. Trypan blue staining was used to observe the implantation site at 5.5 days post-coitum (dpc). Uterine morphology, estradiol (E2) and progesterone levels, and the anti-oxidation system were evaluated at 5.5, 7.5, and 9.5 dpc. The proportion of rats in the VED group exhibiting endometrial bleeding gradually increased (5.9%, 32.3%, and 50%) over three consecutive cycles of pseudopregnancy. Vitamin E levels in the VED group were markedly lower compared to the control group in both the plasma and uterus, while the level of vitamin E in the liver did not differ between the control and VED groups. Spontaneous decidualization in the VED group was validated by histological examination and immunohistochemistry. At 5.5 dpc, the mean serum E2 level in the VED group was more than twice that of the control group. The mean total anti-oxidizing capability, catalase level, and glutathione peroxidase activity were significantly reduced in the decidualized portion of the VED group compared to controls, while the malondialdehyde level was also significantly higher in the decidualized portion of the VED group. We hypothesize that the E2 surge at 5.5 dpc and increasing levels of reactive oxygen species are responsible for spontaneous decidualization in VED rats.

  6. Spontaneous decidualization in pseudopregnant rats with vitamin E deficiency.

    PubMed

    Lang, Nan; Wu, Bin; He, Bin; Wang, Lili; Wang, Jiedong

    2016-05-13

    Successful implantation of an embryo requires adequate depth of invasion in the endometrium, which depends upon decidualization. The aim of the present study was to elucidate why humans experience spontaneous decidualization and menstruation while most other mammals do not. We established a spontaneous decidualization model in pseudopregnant rats with vitamin E deficiency (VED) to investigate mechanisms associated with spontaneous decidualization. Vaginal smears were used to monitor bleeding while vitamin E levels were analyzed with a commercial vitamin E assay kit. Trypan blue staining was used to observe the implantation site at 5.5 days post-coitum (dpc). Uterine morphology, estradiol (E2) and progesterone levels, and the anti-oxidation system were evaluated at 5.5, 7.5, and 9.5 dpc. The proportion of rats in the VED group exhibiting endometrial bleeding gradually increased (5.9%, 32.3%, and 50%) over three consecutive cycles of pseudopregnancy. Vitamin E levels in the VED group were markedly lower compared to the control group in both the plasma and uterus, while the level of vitamin E in the liver did not differ between the control and VED groups. Spontaneous decidualization in the VED group was validated by histological examination and immunohistochemistry. At 5.5 dpc, the mean serum E2 level in the VED group was more than twice that of the control group. The mean total anti-oxidizing capability, catalase level, and glutathione peroxidase activity were significantly reduced in the decidualized portion of the VED group compared to controls, while the malondialdehyde level was also significantly higher in the decidualized portion of the VED group. We hypothesize that the E2 surge at 5.5 dpc and increasing levels of reactive oxygen species are responsible for spontaneous decidualization in VED rats. PMID:27033606

  7. Conditioned craving cues elicit an automatic approach tendency.

    PubMed

    Van Gucht, Dinska; Vansteenwegen, Debora; Van den Bergh, Omer; Beckers, Tom

    2008-10-01

    In two experiments, we used a Pavlovian differential conditioning procedure to induce craving for chocolate. As a result of repeated pairing with chocolate intake, initially neutral cues came to elicit an automatic approach tendency in a speeded stimulus-response compatibility reaction time task. This automatic approach tendency, moreover, seemed to be sensitive to manipulations of extinction and renewal in the Pavlovian conditioning procedure. These findings corroborate and extend previous reports of automatic approach tendencies elicited by substance-relevant cues in addiction, while controlling for alternative accounts for such observations. Moreover, our data lend support to and extend learning models of cue-induced craving and addiction. Finally, we argue that the procedure we present here provides an ecologically valid behavioural tool that allows studying processes involved in cue-induced craving, addiction and relapse without relying on verbal report. PMID:18684435

  8. Expert elicitation for a national-level volcano hazard model

    NASA Astrophysics Data System (ADS)

    Bebbington, Mark; Stirling, Mark; Cronin, Shane; Wang, Ting; Jolly, Gill

    2016-04-01

    The quantification of volcanic hazard at national level is a vital pre-requisite to placing volcanic risk on a platform that permits meaningful comparison with other hazards such as earthquakes. New Zealand has up to a dozen dangerous volcanoes, with the usual mixed degrees of knowledge concerning their temporal and spatial eruptive history. Information on the 'size' of the eruptions, be it in terms of VEI, volume or duration, is sketchy at best. These limitations and the need for a uniform approach lend themselves to a subjective hazard analysis via expert elicitation. Approximately 20 New Zealand volcanologists provided estimates for the size of the next eruption from each volcano and, conditional on this, its location, timing and duration. Opinions were likewise elicited from a control group of statisticians, seismologists and (geo)chemists, all of whom had at least heard the term 'volcano'. The opinions were combined via the Cooke classical method. We will report on the preliminary results from the exercise.

  9. Voltage transients elicited by sudden step-up of auxin

    NASA Technical Reports Server (NTRS)

    Pickard, B. G.

    1984-01-01

    It is hypothesized (i) that the molecular mechanism for the reception of friction and flexure and the mechanism by which auxin enhances ethylene production have in common a release of free calcium into the cytosol, (ii) that elevated cytosolic calcium initiates vesicle exocytosis, and (iii) that the vesicles release a factor or set of factors which depolarizes the plasmalemma and promotes ethylene synthesis. One consequence of such exocytosis should be small, extracellularly observable voltage transients. Transients, ranging in size up to 600 microvolts and possessing risetimes (10-90%) of approximately 200 ms, are known to be elicited in etiolated stems of Pisum sativum L. by friction and are here shown to be elicited by sudden increase of auxin concentration and also by a Ca2+ ionophore.

  10. A Step-Wise Approach to Elicit Triangular Distributions

    NASA Technical Reports Server (NTRS)

    Greenberg, Marc W.

    2013-01-01

    Adapt/combine known methods to demonstrate an expert judgment elicitation process that: 1.Models expert's inputs as a triangular distribution, 2.Incorporates techniques to account for expert bias and 3.Is structured in a way to help justify expert's inputs. This paper will show one way of "extracting" expert opinion for estimating purposes. Nevertheless, as with most subjective methods, there are many ways to do this.

  11. Spontaneous pancreatic islet amyloidosis in 40 baboons.

    PubMed

    Hubbard, G B; Steele, K E; Davis, K J; Leland, M M

    2002-04-01

    Spontaneous amyloidosis occurs in many nonhuman primate species but remains difficult to diagnose and treat. Nonhuman primates continue to offer promise as animal models in which to study amyloidosis in humans. Amyloidosis was not diagnosed clinically but was found histologically in four male and 36 female baboons. The baboons averaged 18 years of age at death (range, 7-28 years). Clinical signs, if present, were hyperglycemia and cachexia. Blood glucose values were elevated in 12 of 30 baboons with available clinical pathology data. Four baboons had been clinically diagnosed as diabetic and three were treated with insulin. Amyloid was found in the islets of Langerhans of the pancreas in 40 baboons; 35 baboons had amyloid only in the islets of Langerhans. Amyloid was found in nonislet tissue of baboons as follows: five, nonislet pancreas; four, intestine and adrenal; three, kidney; two, prostate and spleen; and one each, lymph node, liver, gall bladder, stomach, tongue, urinary bladder, and salivary gland. Sections of paraffin-embedded tissues were evaluated for amyloid with hematoxylin and eosin (HE) and congo red (CR) staining, and using immunohistochemistry for human islet amyloid polypeptide (IAPP), calcitonin gene-related peptide (CGRP), glucagon, pancreatic polypeptide (PP), somatostatin (SS), and porcine insulin. Islet amyloid was positive with HE in 40 baboons, with CR in 39 baboons, and with IAPP and CGRP in 35 baboons. IAPP and CGRP only stained islet amyloid. PP, SS, glucagon, and porcine insulin did not stain amyloid. Islet amyloidosis in the baboon appears to be difficult to diagnose clinically, age-related, and similar to islet amyloidosis in other species. The baboon may be a good model for the study of islet amyloidosis in humans.

  12. Elicitation of macrophages from the peritoneal cavity of channel catfish

    USGS Publications Warehouse

    Jenkins, J.A.; Klesius, P.H.

    1998-01-01

    Four chemicals were evaluated for elicitation of macrophages in peritoneal cavities of 250-300g healthy channel catfish Ictalurus punctatus. Cellular exudates were collected at 3, 5, 7, 10, 14, and 20 d following intraperitoneal injections with squalene, Freund's incomplete adjuvant (FIA), goat serum, thioglycollate, or as a control, phosphate-buffered saline. Injection with either squalene or FIA induced significantly greater (P ??? 0.0001) macrophage recruitment than the other chemicals. The effectiveness of squalene and FIA was compared further by macrophage collection daily for 7 d. Squalene and FIA elicited similarly high macrophage responses (P ??? 0.0450), the highest being 3.43 x 106 macrophages/mL (SE, 2.4 x l06) at 99% purity at day 2 and 2.1 X 106 macrophages/mL (SE, 0.7 x 106) at day 14 at 80% purity, respectively. In both experiments, the time after injection was not statistically significant, nor was there an interaction between time and chemicals. The occurrence of cells other than macrophages decreased with time to yield macrophage recoveries of 47-99% for squalene and 30-80% for FIA. Two subsets of macrophages were observed by means of flow cytometry. As demonstrated by chemiluminescence, the squalene-elicited cells produced high-energy oxygen compounds important to the phagocytic process.

  13. Intrathecal orphenadrine elicits spinal block in the rat.

    PubMed

    Chen, Yu-Wen; Tzeng, Jann-Inn; Chen, Yu-Chung; Hung, Ching-Hsia; Wang, Jhi-Joung

    2014-11-01

    The purpose of this study was to estimate the local anesthetic effect of orphenadrine, an anti-muscarinic agent, in spinal anesthesia and its comparison with the local anesthetic lidocaine. After the rat was injected intrathecally, the spinal block of orphenadrine and lidocaine was constructed in a dosage-dependent fashion. The potency and duration of spinal anesthesia with orphenadrine were compared with that of lidocaine. Our data demonstrated that orphenadrine and lidocaine elicited dose-dependent spinal blockades on the motor function, sensory, and proprioception. On the 50% effective dose (ED50) basis, the ranks of potency in motor function, nociception, and proprioception were orphenadrine>lidocaine (P<0.01). At equipotent doses (ED25, ED50, ED75), the block duration elicited by orphenadrine was greater than that elicited by lidocaine (P<0.01). Orphenadrine, but not lidocaine, exhibited longer duration of nociceptive/sensory blockade than that of motor blockade at equipotent doses. Ineffective-dose orphenadrine as adjuvant did not enhance spinal anesthesia with lidocaine. The preclinical data revealed that orphenadrine with a more sensory-selective action over motor block exhibited more potent and longer spinal anesthesia when compared to lidocaine. PMID:25205132

  14. Elicited versus emitted behavior: Time to abandon the distinction.

    PubMed

    Domjan, Michael

    2016-03-01

    The concept of emitted behavior was formulated as a part of the original argument for the validity of a new kind of learning called operant conditioning. The rationale for operant conditioning contrasted it with Pavlovian or classical conditioning, which was (and remains) fundamentally based on responses to conditioned and unconditioned stimuli. Classical conditioned responses were said to be elicited. In contrast, operant behavior was viewed as emitted and controlled primarily by response consequences rather than antecedents. I argue that the distinction between emitted and elicited behavior is no longer warranted for three major reasons. First, the distinction was based on a view of Pavlovian conditioning that is no longer viable. Second, the distinction is incompatible with both empirical data and contemporary conceptualizations of operant behavior. Third, the only way to overcome these problems is to define emitted and elicited in terms of the type of conditioning (operant and classical) that produces these behaviors, but that approach makes the definitions circular and does not avoid implications of the terms that are misleading and counterproductive in light of contemporary research and thinking. PMID:26872681

  15. Spontaneous fission properties and lifetime systematics

    SciTech Connect

    Hoffman, D.C.

    1989-03-01

    Half-lives for spontaneous fission of nuclides with even and odd numbers of particles are compared with recent theoretical calculations. A summary of odd particle hindrance factors is given. The most recent measurements of kinetic-energy and mass distributions and neutron emission for spontaneous fission of the heaviest nuclides are summarized and discussed. 51 refs., 9 figs.

  16. Spontaneous pneumomediastinum: A complication of swine flu.

    PubMed

    Padhy, Ajit Kumar; Gupta, Anubhav; Aiyer, Palash; Jhajhria, Narender Singh; Grover, Vijay; Gupta, Vijay Kumar

    2015-10-01

    The occurrence of spontaneous pneumomediastinum in swine flu, or H1N1 influenza A infection, is a rare phenomenon and only few cases have been reported in children. We describe a case of spontaneous pneumomediastinum in adult infected with swine flu.

  17. Abstracting in the Context of Spontaneous Learning

    ERIC Educational Resources Information Center

    Williams, Gaye

    2007-01-01

    There is evidence that spontaneous learning leads to relational understanding and high positive affect. To study spontaneous abstracting, a model was constructed by combining the RBC model of abstraction with Krutetskii's mental activities. Using video-stimulated interviews, the model was then used to analyze the behavior of two Year 8 students…

  18. Simultaneous and spontaneous bilateral quadriceps tendons rupture.

    PubMed

    Celik, Evrim Coşkun; Ozbaydar, Mehmet; Ofluoglu, Demet; Demircay, Emre

    2012-07-01

    Simultaneous and spontaneous bilateral quadriceps tendon rupture is an uncommon injury that is usually seen in association with multiple medical conditions and some medications. We report a case of simultaneous and spontaneous bilateral quadriceps tendon rupture that may be related to the long-term use of a statin.

  19. Spontaneity and Equilibrium II: Multireaction Systems

    ERIC Educational Resources Information Center

    Raff, Lionel M.

    2014-01-01

    The thermodynamic criteria for spontaneity and equilibrium in multireaction systems are developed and discussed. When N reactions are occurring simultaneously, it is shown that G and A will depend upon N independent reaction coordinates, ?a (a = 1,2, ..., N), in addition to T and p for G or T and V for A. The general criteria for spontaneity and…