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Sample records for early blindness revealed

  1. Multimodal MR-imaging reveals large-scale structural and functional connectivity changes in profound early blindness

    PubMed Central

    Bauer, Corinna M.; Hirsch, Gabriella V.; Zajac, Lauren; Koo, Bang-Bon; Collignon, Olivier

    2017-01-01

    In the setting of profound ocular blindness, numerous lines of evidence demonstrate the existence of dramatic anatomical and functional changes within the brain. However, previous studies based on a variety of distinct measures have often provided inconsistent findings. To help reconcile this issue, we used a multimodal magnetic resonance (MR)-based imaging approach to provide complementary structural and functional information regarding this neuroplastic reorganization. This included gray matter structural morphometry, high angular resolution diffusion imaging (HARDI) of white matter connectivity and integrity, and resting state functional connectivity MRI (rsfcMRI) analysis. When comparing the brains of early blind individuals to sighted controls, we found evidence of co-occurring decreases in cortical volume and cortical thickness within visual processing areas of the occipital and temporal cortices respectively. Increases in cortical volume in the early blind were evident within regions of parietal cortex. Investigating white matter connections using HARDI revealed patterns of increased and decreased connectivity when comparing both groups. In the blind, increased white matter connectivity (indexed by increased fiber number) was predominantly left-lateralized, including between frontal and temporal areas implicated with language processing. Decreases in structural connectivity were evident involving frontal and somatosensory regions as well as between occipital and cingulate cortices. Differences in white matter integrity (as indexed by quantitative anisotropy, or QA) were also in general agreement with observed pattern changes in the number of white matter fibers. Analysis of resting state sequences showed evidence of both increased and decreased functional connectivity in the blind compared to sighted controls. Specifically, increased connectivity was evident between temporal and inferior frontal areas. Decreases in functional connectivity were observed

  2. Subcortical functional reorganization due to early blindness.

    PubMed

    Coullon, Gaelle S L; Jiang, Fang; Fine, Ione; Watkins, Kate E; Bridge, Holly

    2015-04-01

    Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a "visual" subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. Copyright © 2015 the American Physiological Society.

  3. Subcortical functional reorganization due to early blindness

    PubMed Central

    Jiang, Fang; Fine, Ione; Watkins, Kate E.; Bridge, Holly

    2015-01-01

    Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a “visual” subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. PMID:25673746

  4. Auditory motion processing after early blindness

    PubMed Central

    Jiang, Fang; Stecker, G. Christopher; Fine, Ione

    2014-01-01

    Studies showing that occipital cortex responds to auditory and tactile stimuli after early blindness are often interpreted as demonstrating that early blind subjects “see” auditory and tactile stimuli. However, it is not clear whether these occipital responses directly mediate the perception of auditory/tactile stimuli, or simply modulate or augment responses within other sensory areas. We used fMRI pattern classification to categorize the perceived direction of motion for both coherent and ambiguous auditory motion stimuli. In sighted individuals, perceived motion direction was accurately categorized based on neural responses within the planum temporale (PT) and right lateral occipital cortex (LOC). Within early blind individuals, auditory motion decisions for both stimuli were successfully categorized from responses within the human middle temporal complex (hMT+), but not the PT or right LOC. These findings suggest that early blind responses within hMT+ are associated with the perception of auditory motion, and that these responses in hMT+ may usurp some of the functions of nondeprived PT. Thus, our results provide further evidence that blind individuals do indeed “see” auditory motion. PMID:25378368

  5. Olfactory Performance in a Large Sample of Early-Blind and Late-Blind Individuals.

    PubMed

    Sorokowska, Agnieszka

    2016-10-01

    Previous examinations of olfactory sensitivity in blind people have produced contradictory findings. Thus, whether visual impairment is associated with increased olfactory abilities is unclear. In the present investigation, I aimed to resolve the existing questions via a relatively large-scale study comprising early-blind (N = 43), and late-blind (N = 41) and sighted (N = 84) individuals matched in terms of gender and age. To compare the results with those of previous studies, I combined data from a free odor identification test, extensive psychophysical testing (Sniffin' Sticks test), and self-assessed olfactory performance. The analyses revealed no significant effects of sight on olfactory threshold, odor discrimination, cued identification, or free identification scores; neither was the performance of the early-blind and late-blind participants significantly different. Additionally, the self-assessed olfactory abilities of the blind people were no different than those of the sighted people. These results suggest that sensory compensation in visually impaired is not pronounced with regards to olfactory abilities as measured by standardized smell tests. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Evaluation of the attentional capacities and working memory of early and late blind persons.

    PubMed

    Pigeon, Caroline; Marin-Lamellet, Claude

    2015-02-01

    Although attentional processes and working memory seem to be significantly involved in the daily activities (particularly during navigating) of persons who are blind and who use these abilities to compensate for their lack of vision, few studies have investigated these mechanisms in this population. The aim of this study is to evaluate the selective, sustained and divided attention, attentional inhibition and switching and working memory of blind persons. Early blind, late blind and sighted participants completed neuropsychological tests that were designed or adapted to be achievable in the absence of vision. The results revealed that the early blind participants outperformed the sighted ones in selective, sustained and divided attention and working memory tests, and the late blind participants outperformed the sighted participants in selective, sustained and divided attention. However, no differences were found between the blind groups and the sighted group in the attentional inhibition and switching tests. Furthermore, no differences were found between the early and late blind participants in this set of tests. These results suggest that early and late blind persons can compensate for the lack of vision by an enhancement of the attentional and working memory capacities. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. From Perception to Metacognition: Auditory and Olfactory Functions in Early Blind, Late Blind, and Sighted Individuals

    PubMed Central

    Cornell Kärnekull, Stina; Arshamian, Artin; Nilsson, Mats E.; Larsson, Maria

    2016-01-01

    Although evidence is mixed, studies have shown that blind individuals perform better than sighted at specific auditory, tactile, and chemosensory tasks. However, few studies have assessed blind and sighted individuals across different sensory modalities in the same study. We tested early blind (n = 15), late blind (n = 15), and sighted (n = 30) participants with analogous olfactory and auditory tests in absolute threshold, discrimination, identification, episodic recognition, and metacognitive ability. Although the multivariate analysis of variance (MANOVA) showed no overall effect of blindness and no interaction with modality, follow-up between-group contrasts indicated a blind-over-sighted advantage in auditory episodic recognition, that was most pronounced in early blind individuals. In contrast to the auditory modality, there was no empirical support for compensatory effects in any of the olfactory tasks. There was no conclusive evidence for group differences in metacognitive ability to predict episodic recognition performance. Taken together, the results showed no evidence of an overall superior performance in blind relative sighted individuals across olfactory and auditory functions, although early blind individuals exceled in episodic auditory recognition memory. This observation may be related to an experience-induced increase in auditory attentional capacity. PMID:27729884

  8. Tactile Sensitivity and Braille Reading in People with Early Blindness and Late Blindness

    ERIC Educational Resources Information Center

    Oshima, Kensuke; Arai, Tetsuya; Ichihara, Shigeru; Nakano, Yasushi

    2014-01-01

    Introduction: The inability to read quickly can be a disadvantage throughout life. This study focused on the associations of braille reading fluency and individual factors, such as the age at onset of blindness and number of years reading braille, and the tactile sensitivity of people with early and late blindness. The relationship between reading…

  9. Odour discrimination and identification are improved in early blindness.

    PubMed

    Cuevas, Isabel; Plaza, Paula; Rombaux, Philippe; De Volder, Anne G; Renier, Laurent

    2009-12-01

    Previous studies showed that early blind humans develop superior abilities in the use of their remaining senses, hypothetically due to a functional reorganization of the deprived visual brain areas. While auditory and tactile functions have been investigated for long, little is known about the effects of early visual deprivation on olfactory processing. However, blind humans make an extensive use of olfactory information in their daily life. Here we investigated olfactory discrimination and identification abilities in early blind subjects and age-matched sighted controls. Three levels of cuing were used in the identification task, i.e., free-identification (no cue), categorization (semantic cues) and multiple choice (semantic and phonological cues). Early blind subjects significantly outperformed the controls in odour discrimination, free-identification and categorization. In addition, the larger group difference was observed in the free-identification as compared to the categorization and the multiple choice conditions. This indicated that a better access to the semantic information from odour perception accounted for part of the improved olfactory performances in odour identification in the blind. We concluded that early blind subjects have both improved perceptual abilities and a better access to the information stored in semantic memory than sighted subjects.

  10. Brain Structure Changes Visualized in Early- and Late-Onset Blind Subjects

    PubMed Central

    Leporé, Natasha; Voss, Patrice; Lepore, Franco; Chou, Yi-Yu; Fortin, Madeleine; Gougoux, Frédéric; Lee, Agatha D.; Brun, Caroline; Lassonde, Maryse; Madsen, Sarah K.; Toga, Arthur W.; Thompson, Paul M.

    2009-01-01

    We examine 3D patterns of volume differences in the brain associated with blindness, in subjects grouped according to early and late onset. Using tensor-based morphometry, we map volume reductions and gains in 16 early-onset (EB) and 16 late-onset (LB) blind adults (onset <5 and >14 years old, respectively) relative to 16 matched sighted controls. Each subject’s structural MRI was fluidly registered to a common template. Anatomical differences between groups were mapped based on statistical analysis of the resulting deformation fields revealing profound deficits in primary and secondary visual cortices for both blind groups. Regions outside the occipital lobe showed significant hypertrophy, suggesting widespread compensatory adaptations. EBs but not LBs showed deficits in the splenium and hypertrophy in the isthmus. Gains in the isthmus and non-occipital white matter were more widespread in the EBs. These differences may reflect regional alterations in late neurodevelopmental processes, such as myelination, that continue into adulthood. PMID:19643183

  11. Neural correlates of audiotactile phonetic processing in early-blind readers: an fMRI study.

    PubMed

    Pishnamazi, Morteza; Nojaba, Yasaman; Ganjgahi, Habib; Amousoltani, Asie; Oghabian, Mohammad Ali

    2016-05-01

    Reading is a multisensory function that relies on arbitrary associations between auditory speech sounds and symbols from a second modality. Studies of bimodal phonetic perception have mostly investigated the integration of visual letters and speech sounds. Blind readers perform an analogous task by using tactile Braille letters instead of visual letters. The neural underpinnings of audiotactile phonetic processing have not been studied before. We used functional magnetic resonance imaging to reveal the neural correlates of audiotactile phonetic processing in 16 early-blind Braille readers. Braille letters and corresponding speech sounds were presented in unimodal, and congruent/incongruent bimodal configurations. We also used a behavioral task to measure the speed of blind readers in identifying letters presented via tactile and/or auditory modalities. Reaction times for tactile stimuli were faster. The reaction times for bimodal stimuli were equal to those for the slower auditory-only stimuli. fMRI analyses revealed the convergence of unimodal auditory and unimodal tactile responses in areas of the right precentral gyrus and bilateral crus I of the cerebellum. The left and right planum temporale fulfilled the 'max criterion' for bimodal integration, but activities of these areas were not sensitive to the phonetical congruency between sounds and Braille letters. Nevertheless, congruency effects were found in regions of frontal lobe and cerebellum. Our findings suggest that, unlike sighted readers who are assumed to have amodal phonetic representations, blind readers probably process letters and sounds separately. We discuss that this distinction might be due to mal-development of multisensory neural circuits in early blinds or it might be due to inherent differences between Braille and print reading mechanisms.

  12. Early blindness alters the spatial organization of verbal working memory.

    PubMed

    Bottini, Roberto; Mattioni, Stefania; Collignon, Olivier

    2016-10-01

    Several studies suggest that serial order in working memory (WM) is grounded on space. For a list of ordered items held in WM, items at the beginning of the list are associated with the left side of space and items at the end of the list with the right side. This suggests that maintaining items in verbal WM is performed in strong analogy to writing these items down on a physical whiteboard for later consultation (The Mental Whiteboard Hypothesis). What drives this spatial mapping of ordered series in WM remains poorly understood. In the present study we tested whether visual experience is instrumental in establishing the link between serial order in WM and spatial processing. We tested early blind (EB), late blind (LB) and sighted individuals in an auditory WM task. Replicating previous studies, left-key responses were faster for early items in the list whereas later items facilitated right-key responses in the sighted group. The same effect was observed in LB individuals. In contrast, EB participants did not show any association between space and serial position in WM. These results suggest that early visual experience plays a critical role in linking ordered items in WM and spatial representations. The analogical spatial structure of WM may depend in part on the actual experience of using spatially organized devices (e.g., notes, whiteboards) to offload WM. These practices are largely precluded to EB individuals, who instead rely to mnemonic devices that are less spatially organized (e.g., recordings, vocal notes). The way we habitually organize information in the external world may bias the way we organize information in our WM. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Our Blind Child: Bringing Up a Blind Child During Its Early Years.

    ERIC Educational Resources Information Center

    Pielasch, Helmut, Ed.; And Others

    The document contains 10 author contributed chapters (in four languages) which resulted from a 1976 international symposium on problems concerning the preschool education of blind children and the guidance of their parents. Chapters have the following titles (with authors and nationality in parentheses): "Development of the Blind Child"…

  14. Early but not late-blindness leads to enhanced auditory perception.

    PubMed

    Wan, Catherine Y; Wood, Amanda G; Reutens, David C; Wilson, Sarah J

    2010-01-01

    The notion that blindness leads to superior non-visual abilities has been postulated for centuries. Compared to sighted individuals, blind individuals show different patterns of brain activation when performing auditory tasks. To date, no study has controlled for musical experience, which is known to influence auditory skills. The present study tested 33 blind (11 congenital, 11 early-blind, 11 late-blind) participants and 33 matched sighted controls. We showed that the performance of blind participants was better than that of sighted participants on a range of auditory perception tasks, even when musical experience was controlled for. This advantage was observed only for individuals who became blind early in life, and was even more pronounced for individuals who were blind from birth. Years of blindness did not predict task performance. Here, we provide compelling evidence that superior auditory abilities in blind individuals are not explained by musical experience alone. These results have implications for the development of sensory substitution devices, particularly for late-blind individuals.

  15. Early social-emotional development in blind infants.

    PubMed

    Tröster, H; Brambring, M

    1992-01-01

    In order to study the impact of blindness on social and emotional development during the first year of life, the level of social-emotional development was compared in blind and sighted 9- and 12-month-old infants. The five 9-month-old and the 17 12-month-old blind infants were completely blind from birth and exhibited no further serious disabilities. Social-emotional development was assessed with a scale from the Bielefeld Developmental Test for Blind Infants and Preschoolers containing three subscales on emotions, social interaction and impulse control. Compared to non-disabled infants, blind infants exhibited a more limited repertoire of facial expressions and less responsiveness. They less frequently attempted to initiate contact with their mothers (self-initiated interactions) or comply with simple requests and prohibitions than sighted infants. These differences in the social-emotional development of blind and sighted infants are traced back to the effects of blindness on the mother-child interaction. The lack of visual perception appears to impede particularly the acquisition of a dialogue concept.

  16. Early Interactions with Children Who Are Deaf-Blind

    MedlinePlus

    ... Inclusion IDEA (Individuals with Disabilities Education Act) Assistive Technology History of Deaf-Blind Education Transition to Adulthood > Transition Self Determination Person Centered Planning Postsecondary Education Independent Living ... > Intervener Services Support Service Provider Personnel Development & ...

  17. Functional photoreceptor loss revealed with adaptive optics: an alternate cause of color blindness.

    PubMed

    Carroll, Joseph; Neitz, Maureen; Hofer, Heidi; Neitz, Jay; Williams, David R

    2004-06-01

    There is enormous variation in the X-linked L/M (long/middle wavelength sensitive) gene array underlying "normal" color vision in humans. This variability has been shown to underlie individual variation in color matching behavior. Recently, red-green color blindness has also been shown to be associated with distinctly different genotypes. This has opened the possibility that there may be important phenotypic differences within classically defined groups of color blind individuals. Here, adaptive optics retinal imaging has revealed a mechanism for producing dichromatic color vision in which the expression of a mutant cone photopigment gene leads to the loss of the entire corresponding class of cone photoreceptor cells. Previously, the theory that common forms of inherited color blindness could be caused by the loss of photoreceptor cells had been discounted. We confirm that remarkably, this loss of one-third of the cones does not impair any aspect of vision other than color.

  18. Early blindness and coma during intrathecal chemotherapy for meningeal carcinomatosis.

    PubMed

    Boogerd, W; Moffie, D; Smets, L A

    1990-02-01

    A 35-year-old woman was treated with intraventricular methotrexate (MTX) with a total dose of 70 mg followed by cytosine arabinoside (Ara-C) with a total dose of 80 mg for meningeal metastasis of breast carcinoma. Radiation therapy was not given. Despite a response of the meningeal tumor the patient developed in the third week of MTX treatment a progressive visual loss and loss of consciousness which worsened during subsequent Ara-C treatment and led to death within 3 weeks. Postmortem examination revealed only minimal neoplastic infiltration of the meninges. Multiple foci of axonal degeneration and demyelination were found in the optic nerves and chiasm, the superficial layers of the brainstem, and spinal cord and to some extent in other cranial nerves and spinal nerve roots. The possible causes of this previously unreported early complication are discussed.

  19. Blindness

    MedlinePlus

    ... is to “conduct and support research, training, health information dissemination, and other programs with respect to blinding eye ... Media Policies and Other Important Links NEI Employee Emergency Information NEI Intranet (Employees Only) *PDF files require ...

  20. Alexia for Braille following bilateral occipital stroke in an early blind woman.

    PubMed

    Hamilton, R; Keenan, J P; Catala, M; Pascual-Leone, A

    2000-02-07

    Recent functional imaging and neurophysiologic studies indicate that the occipital cortex may play a role in Braille reading in congenitally and early blind subjects. We report on a woman blind from birth who sustained bilateral occipital damage following an ischemic stroke. Prior to the stroke, the patient was a proficient Braille reader. Following the stroke, she was no longer able to read Braille yet her somatosensory perception appeared otherwise to be unchanged. This case supports the emerging evidence for the recruitment of striate and prestriate cortex for Braille reading in early blind subjects.

  1. Cortical Plasticity and Olfactory Function in Early Blindness

    PubMed Central

    Araneda, Rodrigo; Renier, Laurent A.; Rombaux, Philippe; Cuevas, Isabel; De Volder, Anne G.

    2016-01-01

    Over the last decade, functional brain imaging has provided insight to the maturation processes and has helped elucidate the pathophysiological mechanisms involved in brain plasticity in the absence of vision. In case of congenital blindness, drastic changes occur within the deafferented “visual” cortex that starts receiving and processing non visual inputs, including olfactory stimuli. This functional reorganization of the occipital cortex gives rise to compensatory perceptual and cognitive mechanisms that help blind persons achieve perceptual tasks, leading to superior olfactory abilities in these subjects. This view receives support from psychophysical testing, volumetric measurements and functional brain imaging studies in humans, which are presented here. PMID:27625596

  2. Cortical plasticity and preserved function in early blindness

    PubMed Central

    Renier, Laurent; De Volder, Anne G.; Rauschecker, Josef P.

    2013-01-01

    The “neural Darwinism” theory predicts that when one sensory modality is lacking, as in congenital blindness, the target structures are taken over by the afferent inputs from other senses that will promote and control their functional maturation (Edelman, 1993). This view receives support from both cross-modal plasticity experiments in animal models and functional imaging studies in man, which are presented here. PMID:23453908

  3. The Early Use of Blinding in Therapeutic Clinical Research of Neurological Disorders

    PubMed Central

    Jensen, Matthew B.; Janik, Erika L.; Waclawik, Andrew J.

    2016-01-01

    We sought to identify early uses of blinding in therapeutic clinical trials of neurological disorders by multiple search methods. A 1784 report by Benjamin Franklin and others described the evaluation of the use of Mesmerism to treat neurological and other syndromes including headache and epilepsy, using blindfolds and screens. This report demonstrated the usefulness of blinding to reduce bias in clinical research, yet despite this early discovery, blinding was not widely accepted or routinely used until the 20th century. Blinded clinical trials began to be used for various neurological syndromes in the 1950s, sporadically at first and then increasing in frequency in subsequent years. The reason for this delay is unclear, but we propose several hypotheses. PMID:27617324

  4. Blindness and social trust: The effect of early visual deprivation on judgments of trustworthiness.

    PubMed

    Ferrari, C; Vecchi, T; Merabet, L B; Cattaneo, Z

    2017-10-01

    Investigating the impact of early visual deprivation on evaluations related to social trust has received little attention to date. This is despite consistent evidence suggesting that early onset blindness may interfere with the normal development of social skills. In this study, we investigated whether early blindness affects judgments of trustworthiness regarding the actions of an agent, with trustworthiness representing the fundamental dimension in the social evaluation. Specifically, we compared performance between a group of early blind individuals with that of sighted controls in their evaluation of trustworthiness of an agent after hearing a pair of two positive or two negative social behaviors (impression formation). Participants then repeated the same evaluation following the presentation of a third (consistent or inconsistent) behavior regarding the same agent (impression updating). Overall, blind individuals tended to give similar evaluations compared to their sighted counterparts. However, they also valued positive behaviors significantly more than sighted controls when forming their impression of an agent's trustworthiness. Moreover, when inconsistent information was provided, blind individuals were more prone to revise their initial evaluation compared to controls. These results suggest that early visual deprivation may have a dramatic effect on the evaluation of social factors such as trustworthiness. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Irrelevant speech does not interfere with serial recall in early blind listeners.

    PubMed

    Kattner, Florian; Ellermeier, Wolfgang

    2014-01-01

    Phonological working memory is known be (a) inversely related to the duration of the items to be learned (word-length effect), and (b) impaired by the presence of irrelevant speech-like sounds (irrelevant-speech effect). As it is discussed controversially whether these memory disruptions are subject to attentional control, both effects were studied in sighted participants and in a sample of early blind individuals who are expected to be superior in selectively attending to auditory stimuli. Results show that, while performance depended on word length in both groups, irrelevant speech interfered with recall only in the sighted group, but not in blind participants. This suggests that blind listeners may be able to effectively prevent irrelevant sound from being encoded in the phonological store, presumably due to superior auditory processing. The occurrence of a word-length effect, however, implies that blind and sighted listeners are utilizing the same phonological rehearsal mechanism in order to maintain information in the phonological store.

  6. Early Blindness Results in Developmental Plasticity for Auditory Motion Processing within Auditory and Occipital Cortex

    PubMed Central

    Jiang, Fang; Stecker, G. Christopher; Boynton, Geoffrey M.; Fine, Ione

    2016-01-01

    Early blind subjects exhibit superior abilities for processing auditory motion, which are accompanied by enhanced BOLD responses to auditory motion within hMT+ and reduced responses within right planum temporale (rPT). Here, by comparing BOLD responses to auditory motion in hMT+ and rPT within sighted controls, early blind, late blind, and sight-recovery individuals, we were able to separately examine the effects of developmental and adult visual deprivation on cortical plasticity within these two areas. We find that both the enhanced auditory motion responses in hMT+ and the reduced functionality in rPT are driven by the absence of visual experience early in life; neither loss nor recovery of vision later in life had a discernable influence on plasticity within these areas. Cortical plasticity as a result of blindness has generally be presumed to be mediated by competition across modalities within a given cortical region. The reduced functionality within rPT as a result of early visual loss implicates an additional mechanism for cross modal plasticity as a result of early blindness—competition across different cortical areas for functional role. PMID:27458357

  7. Neural Correlates of Natural Human Echolocation in Early and Late Blind Echolocation Experts

    PubMed Central

    Thaler, Lore; Arnott, Stephen R.; Goodale, Melvyn A.

    2011-01-01

    Background A small number of blind people are adept at echolocating silent objects simply by producing mouth clicks and listening to the returning echoes. Yet the neural architecture underlying this type of aid-free human echolocation has not been investigated. To tackle this question, we recruited echolocation experts, one early- and one late-blind, and measured functional brain activity in each of them while they listened to their own echolocation sounds. Results When we compared brain activity for sounds that contained both clicks and the returning echoes with brain activity for control sounds that did not contain the echoes, but were otherwise acoustically matched, we found activity in calcarine cortex in both individuals. Importantly, for the same comparison, we did not observe a difference in activity in auditory cortex. In the early-blind, but not the late-blind participant, we also found that the calcarine activity was greater for echoes reflected from surfaces located in contralateral space. Finally, in both individuals, we found activation in middle temporal and nearby cortical regions when they listened to echoes reflected from moving targets. Conclusions These findings suggest that processing of click-echoes recruits brain regions typically devoted to vision rather than audition in both early and late blind echolocation experts. PMID:21633496

  8. Comparison of auditory stream segregation in sighted and early blind individuals.

    PubMed

    Boroujeni, Fatemeh Moghadasi; Heidari, Fatemeh; Rouzbahani, Masoumeh; Kamali, Mohammad

    2017-01-18

    An important characteristic of the auditory system is the capacity to analyze complex sounds and make decisions on the source of the constituent parts of these sounds. Blind individuals compensate for the lack of visual information by an increase input from other sensory modalities, including increased auditory information. The purpose of the current study was to compare the fission boundary (FB) threshold of sighted and early blind individuals through spectral aspects using a psychoacoustic auditory stream segregation (ASS) test. This study was conducted on 16 sighted and 16 early blind adult individuals. The applied stimuli were presented sequentially as the pure tones A and B and as a triplet ABA-ABA pattern at the intensity of 40dBSL. The A tone frequency was selected as the basis at values of 500, 1000, and 2000Hz. The B tone was presented with the difference of a 4-100% above the basis tone frequency. Blind individuals had significantly lower FB thresholds than sighted people. FB was independent of the frequency of the tone A when expressed as the difference in the number of equivalent rectangular bandwidths (ERBs). Early blindness may increase perceptual separation of the acoustic stimuli to form accurate representations of the world. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Early Language Development in Blind and Severely Visually Impaired Children. Interim Report on Pilot Study.

    ERIC Educational Resources Information Center

    Moore, Vanessa; McConachie, Helen

    This study investigated variables that might be associated with outcome differences in language development of 10 children (ages 10-20 months) with blindness or severe visual impairments, attending a developmental vision clinic in southern England. Subjects' early patterns of expressive language development were examined and related to observed…

  10. Psychic blindness or visual agnosia: early descriptions of a nervous disorder.

    PubMed

    Baumann, Christian

    2011-01-01

    This article briefly reports on three early contributions to the understanding of visual agnosia as a syndrome sui generis. The authors of the respective papers worked in different fields such as physiology, ophthalmology, and neurology, and, although they were not in direct contact with each other, their results converged upon a consistent view of a nervous disorder that they called psychic blindness.

  11. Reduction of Interhemispheric Functional Brain Connectivity in Early Blindness: A Resting-State fMRI Study

    PubMed Central

    2017-01-01

    Objective The purpose of this study was to investigate the resting-state interhemispheric functional connectivity in early blindness by using voxel-mirrored homotopic connectivity (VMHC). Materials and Methods Sixteen early blind patients (EB group) and sixteen age- and gender-matched sighted control volunteers (SC group) were recruited in this study. We used VMHC to identify brain areas with significant differences in functional connectivity between different groups and used voxel-based morphometry (VBM) to calculate the individual gray matter volume (GMV). Results VMHC analysis showed a significantly lower connectivity in primary visual cortex, visual association cortex, and somatosensory association cortex in EB group compared to sighted controls. Additionally, VBM analysis revealed that GMV was reduced in the left lateral calcarine cortices in EB group compared to sighted controls, while it was increased in the left lateral middle occipital gyri. Statistical analysis showed the duration of blindness negatively correlated with VMHC in the bilateral middle frontal gyri, middle temporal gyri, and inferior temporal gyri. Conclusions Our findings help elucidate the pathophysiological mechanisms of EB. The interhemispheric functional connectivity was impaired in EB patients. Additionally, the middle frontal gyri, middle temporal gyri, and inferior temporal gyri may be potential target regions for rehabilitation. PMID:28656145

  12. Do People Who Became Blind Early in Life Develop a Better Sense of Smell? A Psychophysical Study

    ERIC Educational Resources Information Center

    Cuevas, Isabel; Plaza, Paula; Rombaux, Phillippe; Collignon, Olivier; De Volder, Anne G.; Renier, Laurent

    2010-01-01

    Using a set of psychophysical tests, we compared the olfactory abilities of 8 persons who became blind early in life and 16 sighted persons in a control group who were matched for age, sex, and handedness. The results indicated that those who became blind early in life developed compensatory perceptual mechanisms in the olfactory domain that…

  13. Early auditory processing in area V5/MT+ of the congenitally blind brain.

    PubMed

    Watkins, Kate E; Shakespeare, Timothy J; O'Donoghue, M Clare; Alexander, Iona; Ragge, Nicola; Cowey, Alan; Bridge, Holly

    2013-11-13

    Previous imaging studies of congenital blindness have studied individuals with heterogeneous causes of blindness, which may influence the nature and extent of cross-modal plasticity. Here, we scanned a homogeneous group of blind people with bilateral congenital anophthalmia, a condition in which both eyes fail to develop, and, as a result, the visual pathway is not stimulated by either light or retinal waves. This model of congenital blindness presents an opportunity to investigate the effects of very early visual deafferentation on the functional organization of the brain. In anophthalmic animals, the occipital cortex receives direct subcortical auditory input. We hypothesized that this pattern of subcortical reorganization ought to result in a topographic mapping of auditory frequency information in the occipital cortex of anophthalmic people. Using functional MRI, we examined auditory-evoked activity to pure tones of high, medium, and low frequencies. Activity in the superior temporal cortex was significantly reduced in anophthalmic compared with sighted participants. In the occipital cortex, a region corresponding to the cytoarchitectural area V5/MT+ was activated in the anophthalmic participants but not in sighted controls. Whereas previous studies in the blind indicate that this cortical area is activated to auditory motion, our data show it is also active for trains of pure tone stimuli and in some anophthalmic participants shows a topographic mapping (tonotopy). Therefore, this region appears to be performing early sensory processing, possibly served by direct subcortical input from the pulvinar to V5/MT+.

  14. Enhanced perception of pitch changes in speech and music in early blind adults.

    PubMed

    Arnaud, Laureline; Gracco, Vincent; Ménard, Lucie

    2018-06-12

    It is well known that congenitally blind adults have enhanced auditory processing for some tasks. For instance, they show supra-normal capacity to perceive accelerated speech. However, only a few studies have investigated basic auditory processing in this population. In this study, we investigated if pitch processing enhancement in the blind is a domain-general or domain-specific phenomenon, and if pitch processing shares the same properties as in the sighted regarding how scores from different domains are associated. Fifteen congenitally blind adults and fifteen sighted adults participated in the study. We first created a set of personalized native and non-native vowel stimuli using an identification and rating task. Then, an adaptive discrimination paradigm was used to determine the frequency difference limen for pitch direction identification of speech (native and non-native vowels) and non-speech stimuli (musical instruments and pure tones). The results show that the blind participants had better discrimination thresholds than controls for native vowels, music stimuli, and pure tones. Whereas within the blind group, the discrimination thresholds were smaller for musical stimuli than speech stimuli, replicating previous findings in sighted participants, we did not find this effect in the current control group. Further analyses indicate that older sighted participants show higher thresholds for instrument sounds compared to speech sounds. This effect of age was not found in the blind group. Moreover, the scores across domains were not associated to the same extent in the blind as they were in the sighted. In conclusion, in addition to providing further evidence of compensatory auditory mechanisms in early blind individuals, our results point to differences in how auditory processing is modulated in this population. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. The effect of hand movements on numerical bisection judgments in early blind and sighted individuals.

    PubMed

    Rinaldi, Luca; Vecchi, Tomaso; Fantino, Micaela; Merabet, Lotfi B; Cattaneo, Zaira

    2015-10-01

    Recent evidence suggests that in representing numbers blind individuals might be affected differently by proprioceptive cues (e.g., hand positions, head turns) than are sighted individuals. In this study, we asked a group of early blind and sighted individuals to perform a numerical bisection task while executing hand movements in left or right peripersonal space and with either hand. We found that in bisecting ascending numerical intervals, the hemi-space in which the hand was moved (but not the moved hand itself) influenced the bisection bias similarly in both early blind and sighted participants. However, when numerical intervals were presented in descending order, the moved hand (and not the hemi-space in which it was moved) affected the bisection bias in all participants. Overall, our data show that the operation to be performed on the mental number line affects the activated spatial reference frame, regardless of participants' previous visual experience. In particular, both sighted and early blind individuals' representation of numerical magnitude is mainly rooted in world-centered coordinates when numerical information is given in canonical orientation (i.e., from small to large), whereas hand-centered coordinates become more relevant when the scanning of the mental number line proceeds in non-canonical direction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. The effect of hand movements on numerical bisection judgments in early blind and sighted individuals

    PubMed Central

    Rinaldi, Luca; Vecchi, Tomaso; Fantino, Micaela; Merabet, Lotfi B.; Cattaneo, Zaira

    2017-01-01

    Recent evidence suggests that in representing numbers blind individuals might be affected differently by proprioceptive cues (e.g., hand positions, head turns) than are sighted individuals. In this study, we asked a group of early blind and sighted individuals to perform a numerical bisection task while executing hand movements in left or right peripersonal space and with either hand. We found that in bisecting ascending numerical intervals, the hemi-space in which the hand was moved (but not the moved hand itself) influenced the bisection bias similarly in both early blind and sighted participants. However, when numerical intervals were presented in descending order, the moved hand (and not the hemi-space in which it was moved) affected the bisection bias in all participants. Overall, our data show that the operation to be performed on the mental number line affects the activated spatial reference frame, regardless of participants’ previous visual experience. In particular, both sighted and early blind individuals’ representation of numerical magnitude is mainly rooted in world-centered coordinates when numerical information is given in canonical orientation (i.e. from small to large), whereas hand-centered coordinates become more relevant when the scanning of the mental number line proceeds in non-canonical direction. PMID:26184675

  17. Differences between early-blind, late-blind, and blindfolded-sighted people in haptic spatial-configuration learning and resulting memory traces.

    PubMed

    Postma, Albert; Zuidhoek, Sander; Noordzij, Matthijs L; Kappers, Astrid M L

    2007-01-01

    The roles of visual and haptic experience in different aspects of haptic processing of objects in peripersonal space are examined. In three trials, early-blind, late-blind, and blindfolded-sighted individuals had to match ten shapes haptically to the cut-outs in a board as fast as possible. Both blind groups were much faster than the sighted in all three trials. All three groups improved considerably from trial to trial. In particular, the sighted group showed a strong improvement from the first to the second trial. While superiority of the blind remained for speeded matching after rotation of the stimulus frame, coordinate positional-memory scores in a non-speeded free-recall trial showed no significant differences between the groups. Moreover, when assessed with a verbal response, categorical spatial-memory appeared strongest in the late-blind group. The role of haptic and visual experience thus appears to depend on the task aspect tested.

  18. Blind Babies Play Program: A Model for Affordable, Sustainable Early Childhood Literacy Intervention through Play and Socialization

    ERIC Educational Resources Information Center

    Jacko, Virginia A.; Mayros, Roxann; Brady-Simmons, Carol; Chica, Isabel; Moore, J. Elton

    2013-01-01

    The Miami Lighthouse, in its 81 years of service to persons who are visually impaired (that is, those who are blind or have low vision), has adapted to meet the ever-changing needs of clients of all ages. To meet the significant needs of visually impaired children--more than 80% of early learning is visual (Blind Babies Foundation, 2012)--the…

  19. Urine Metabonomics Reveals Early Biomarkers in Diabetic Cognitive Dysfunction.

    PubMed

    Song, Lili; Zhuang, Pengwei; Lin, Mengya; Kang, Mingqin; Liu, Hongyue; Zhang, Yuping; Yang, Zhen; Chen, Yunlong; Zhang, Yanjun

    2017-09-01

    Recently, increasing attention has been paid to diabetic encephalopathy, which is a frequent diabetic complication and affects nearly 30% of diabetics. Because cognitive dysfunction from diabetic encephalopathy might develop into irreversible dementia, early diagnosis and detection of this disease is of great significance for its prevention and treatment. This study is to investigate the early specific metabolites biomarkers in urine prior to the onset of diabetic cognitive dysfunction (DCD) by using metabolomics technology. An ultra-high performance liquid-chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) platform was used to analyze the urine samples from diabetic mice that were associated with mild cognitive impairment (MCI) and nonassociated with MCI in the stage of diabetes (prior to the onset of DCD). We then screened and validated the early biomarkers using OPLS-DA model and support vector machine (SVM) method. Following multivariate statistical and integration analysis, we found that seven metabolites could be accepted as early biomarkers of DCD, and the SVM results showed that the prediction accuracy is as high as 91.66%. The identities of four biomarkers were determined by mass spectrometry. The identified biomarkers were largely involved in nicotinate and nicotinamide metabolism, glutathione metabolism, tryptophan metabolism, and sphingolipid metabolism. The present study first revealed reliable biomarkers for early diagnosis of DCD. It provides new insight and strategy for the early diagnosis and treatment of DCD.

  20. Early but not late blindness leads to enhanced arithmetic and working memory abilities.

    PubMed

    Dormal, Valérie; Crollen, Virginie; Baumans, Christine; Lepore, Franco; Collignon, Olivier

    2016-10-01

    Behavioural and neurophysiological evidence suggest that vision plays an important role in the emergence and development of arithmetic abilities. However, how visual deprivation impacts on the development of arithmetic processing remains poorly understood. We compared the performances of early (EB), late blind (LB) and sighted control (SC) individuals during various arithmetic tasks involving addition, subtraction and multiplication of various complexities. We also assessed working memory (WM) performances to determine if they relate to a blind person's arithmetic capacities. Results showed that EB participants performed better than LB and SC in arithmetic tasks, especially in conditions in which verbal routines and WM abilities are needed. Moreover, EB participants also showed higher WM abilities. Together, our findings demonstrate that the absence of developmental vision does not prevent the development of refined arithmetic skills and can even trigger the refinement of these abilities in specific tasks. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Differential occipital responses in early- and late-blind individuals during a sound-source discrimination task.

    PubMed

    Voss, Patrice; Gougoux, Frederic; Zatorre, Robert J; Lassonde, Maryse; Lepore, Franco

    2008-04-01

    Blind individuals do not necessarily receive more auditory stimulation than sighted individuals. However, to interact effectively with their environment, they have to rely on non-visual cues (in particular auditory) to a greater extent. Often benefiting from cerebral reorganization, they not only learn to rely more on such cues but also may process them better and, as a result, demonstrate exceptional abilities in auditory spatial tasks. Here we examine the effects of blindness on brain activity, using positron emission tomography (PET), during a sound-source discrimination task (SSDT) in both early- and late-onset blind individuals. This should not only provide an answer to the question of whether the blind manifest changes in brain activity but also allow a direct comparison of the two subgroups performing an auditory spatial task. The task was presented under two listening conditions: one binaural and one monaural. The binaural task did not show any significant behavioural differences between groups, but it demonstrated striate and extrastriate activation in the early-blind groups. A subgroup of early-blind individuals, on the other hand, performed significantly better than all the other groups during the monaural task, and these enhanced skills were correlated with elevated activity within the left dorsal extrastriate cortex. Surprisingly, activation of the right ventral visual pathway, which was significantly activated in the late-blind individuals during the monaural task, was negatively correlated with performance. This suggests the possibility that not all cross-modal plasticity is beneficial. Overall, our results not only support previous findings showing that occipital cortex of early-blind individuals is functionally engaged in spatial auditory processing but also shed light on the impact the age of onset of blindness can have on the ensuing cross-modal plasticity.

  2. Adaptive changes in early and late blind: a fMRI study of Braille reading.

    PubMed

    Burton, H; Snyder, A Z; Conturo, T E; Akbudak, E; Ollinger, J M; Raichle, M E

    2002-01-01

    Braille reading depends on remarkable adaptations that connect the somatosensory system to language. We hypothesized that the pattern of cortical activations in blind individuals reading Braille would reflect these adaptations. Activations in visual (occipital-temporal), frontal-language, and somatosensory cortex in blind individuals reading Braille were examined for evidence of differences relative to previously reported studies of sighted subjects reading print or receiving tactile stimulation. Nine congenitally blind and seven late-onset blind subjects were studied with fMRI as they covertly performed verb generation in response to reading Braille embossed nouns. The control task was reading the nonlexical Braille string "######". This study emphasized image analysis in individual subjects rather than pooled data. Group differences were examined by comparing magnitudes and spatial extent of activated regions first determined to be significant using the general linear model. The major adaptive change was robust activation of visual cortex despite the complete absence of vision in all subjects. This included foci in peri-calcarine, lingual, cuneus and fusiform cortex, and in the lateral and superior occipital gyri encompassing primary (V1), secondary (V2), and higher tier (VP, V4v, LO and possibly V3A) visual areas previously identified in sighted subjects. Subjects who never had vision differed from late blind subjects in showing even greater activity in occipital-temporal cortex, provisionally corresponding to V5/MT and V8. In addition, the early blind had stronger activation of occipital cortex located contralateral to the hand used for reading Braille. Responses in frontal and parietal cortex were nearly identical in both subject groups. There was no evidence of modifications in frontal cortex language areas (inferior frontal gyrus and dorsolateral prefrontal cortex). Surprisingly, there was also no evidence of an adaptive expansion of the somatosensory or

  3. Adaptive Changes in Early and Late Blind: A fMRI Study of Braille Reading

    PubMed Central

    SNYDER, A. Z.; CONTURO, T. E.; AKBUDAK, E.; OLLINGER, J. M.; RAICHLE, M. E.

    2013-01-01

    Braille reading depends on remarkable adaptations that connect the somatosensory system to language. We hypothesized that the pattern of cortical activations in blind individuals reading Braille would reflect these adaptations. Activations in visual (occipital-temporal), frontal-language, and somatosensory cortex in blind individuals reading Braille were examined for evidence of differences relative to previously reported studies of sighted subjects reading print or receiving tactile stimulation. Nine congenitally blind and seven late-onset blind subjects were studied with fMRI as they covertly performed verb generation in response to reading Braille embossed nouns. The control task was reading the nonlexical Braille string “######”. This study emphasized image analysis in individual subjects rather than pooled data. Group differences were examined by comparing magnitudes and spatial extent of activated regions first determined to be significant using the general linear model. The major adaptive change was robust activation of visual cortex despite the complete absence of vision in all subjects. This included foci in peri-calcarine, lingual, cuneus and fusiform cortex, and in the lateral and superior occipital gyri encompassing primary (V1), secondary (V2), and higher tier (VP, V4v, LO and possibly V3A) visual areas previously identified in sighted subjects. Subjects who never had vision differed from late blind subjects in showing even greater activity in occipital-temporal cortex, provisionally corresponding to V5/MT and V8. In addition, the early blind had stronger activation of occipital cortex located contralateral to the hand used for reading Braille. Responses in frontal and parietal cortex were nearly identical in both subject groups. There was no evidence of modifications in frontal cortex language areas (inferior frontal gyrus and dorsolateral prefrontal cortex). Surprisingly, there was also no evidence of an adaptive expansion of the somatosensory or

  4. Vibrotactile masking experiments reveal accelerated somatosensory processing in congenitally blind braille readers.

    PubMed

    Bhattacharjee, Arindam; Ye, Amanda J; Lisak, Joy A; Vargas, Maria G; Goldreich, Daniel

    2010-10-27

    Braille reading is a demanding task that requires the identification of rapidly varying tactile patterns. During proficient reading, neighboring characters impact the fingertip at ∼100 ms intervals, and adjacent raised dots within a character at 50 ms intervals. Because the brain requires time to interpret afferent sensorineural activity, among other reasons, tactile stimuli separated by such short temporal intervals pose a challenge to perception. How, then, do proficient Braille readers successfully interpret inputs arising from their fingertips at such rapid rates? We hypothesized that somatosensory perceptual consolidation occurs more rapidly in proficient Braille readers. If so, Braille readers should outperform sighted participants on masking tasks, which demand rapid perceptual processing, but would not necessarily outperform the sighted on tests of simple vibrotactile sensitivity. To investigate, we conducted two-interval forced-choice vibrotactile detection, amplitude discrimination, and masking tasks on the index fingertips of 89 sighted and 57 profoundly blind humans. Sighted and blind participants had similar unmasked detection (25 ms target tap) and amplitude discrimination (compared with 100 μm reference tap) thresholds, but congenitally blind Braille readers, the fastest readers among the blind participants, exhibited significantly less masking than the sighted (masker, 50 Hz, 50 μm; target-masker delays, ±50 and ±100 ms). Indeed, Braille reading speed correlated significantly and specifically with masking task performance, and in particular with the backward masking decay time constant. We conclude that vibrotactile sensitivity is unchanged but that perceptual processing is accelerated in congenitally blind Braille readers.

  5. Vibrotactile masking experiments reveal accelerated somatosensory processing in congenitally blind Braille readers

    PubMed Central

    Bhattacharjee, Arindam; Ye, Amanda J.; Lisak, Joy A.; Vargas, Maria G.; Goldreich, Daniel

    2010-01-01

    Braille reading is a demanding task that requires the identification of rapidly varying tactile patterns. During proficient reading, neighboring characters impact the fingertip at about 100-ms intervals, and adjacent raised dots within a character at 50-ms intervals. Because the brain requires time to interpret afferent sensorineural activity, among other reasons, tactile stimuli separated by such short temporal intervals pose a challenge to perception. How, then, do proficient Braille readers successfully interpret inputs arising from their fingertips at such rapid rates? We hypothesized that somatosensory perceptual consolidation occurs more rapidly in proficient Braille readers. If so, Braille readers should outperform sighted participants on masking tasks, which demand rapid perceptual processing, but would not necessarily outperform the sighted on tests of simple vibrotactile sensitivity. To investigate, we conducted two-interval forced-choice vibrotactile detection, amplitude discrimination, and masking tasks on the index fingertips of 89 sighted and 57 profoundly blind humans. Sighted and blind participants had similar unmasked detection (25-ms target tap) and amplitude discrimination (compared to 100-micron reference tap) thresholds, but congenitally blind Braille readers, the fastest readers among the blind participants, exhibited significantly less masking than the sighted (masker: 50-Hz, 50-micron; target-masker delays ±50 and ±100 ms). Indeed, Braille reading speed correlated significantly and specifically with masking task performance, and in particular with the backward masking decay time constant. We conclude that vibrotactile sensitivity is unchanged, but that perceptual processing is accelerated in congenitally blind Braille readers. PMID:20980584

  6. Event-related potentials reveal rapid registration of features of infrequent changes during change blindness

    PubMed Central

    2010-01-01

    Background Change blindness refers to a failure to detect changes between consecutively presented images separated by, for example, a brief blank screen. As an explanation of change blindness, it has been suggested that our representations of the environment are sparse outside focal attention and even that changed features may not be represented at all. In order to find electrophysiological evidence of neural representations of changed features during change blindness, we recorded event-related potentials (ERPs) in adults in an oddball variant of the change blindness flicker paradigm. Methods ERPs were recorded when subjects performed a change detection task in which the modified images were infrequently interspersed (p = .2) among the frequently (p = .8) presented unmodified images. Responses to modified and unmodified images were compared in the time window of 60-100 ms after stimulus onset. Results ERPs to infrequent modified images were found to differ in amplitude from those to frequent unmodified images at the midline electrodes (Fz, Pz, Cz and Oz) at the latency of 60-100 ms even when subjects were unaware of changes (change blindness). Conclusions The results suggest that the brain registers changes very rapidly, and that changed features in images are neurally represented even without participants' ability to report them. PMID:20181126

  7. Psychophysical "blinding" methods reveal a functional hierarchy of unconscious visual processing.

    PubMed

    Breitmeyer, Bruno G

    2015-09-01

    Numerous non-invasive experimental "blinding" methods exist for suppressing the phenomenal awareness of visual stimuli. Not all of these suppressive methods occur at, and thus index, the same level of unconscious visual processing. This suggests that a functional hierarchy of unconscious visual processing can in principle be established. The empirical results of extant studies that have used a number of different methods and additional reasonable theoretical considerations suggest the following tentative hierarchy. At the highest levels in this hierarchy is unconscious processing indexed by object-substitution masking. The functional levels indexed by crowding, the attentional blink (and other attentional blinding methods), backward pattern masking, metacontrast masking, continuous flash suppression, sandwich masking, and single-flash interocular suppression, fall at progressively lower levels, while unconscious processing at the lowest levels is indexed by eye-based binocular-rivalry suppression. Although unconscious processing levels indexed by additional blinding methods is yet to be determined, a tentative placement at lower levels in the hierarchy is also given for unconscious processing indexed by Troxler fading and adaptation-induced blindness, and at higher levels in the hierarchy indexed by attentional blinding effects in addition to the level indexed by the attentional blink. The full mapping of levels in the functional hierarchy onto cortical activation sites and levels is yet to be determined. The existence of such a hierarchy bears importantly on the search for, and the distinctions between, neural correlates of conscious and unconscious vision. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Recognition Memory for Braille or Spoken Words: An fMRI study in Early Blind

    PubMed Central

    Burton, Harold; Sinclair, Robert J.; Agato, Alvin

    2012-01-01

    We examined cortical activity in early blind during word recognition memory. Nine participants were blind at birth and one by 1.5 yrs. In an event-related design, we studied blood oxygen level-dependent responses to studied (“old”) compared to novel (“new”) words. Presentation mode was in Braille or spoken. Responses were larger for identified “new” words read with Braille in bilateral lower and higher tier visual areas and primary somatosensory cortex. Responses to spoken “new” words were larger in bilateral primary and accessory auditory cortex. Auditory cortex was unresponsive to Braille words and occipital cortex responded to spoken words but not differentially with “old”/“new” recognition. Left dorsolateral prefrontal cortex had larger responses to “old” words only with Braille. Larger occipital cortex responses to “new” Braille words suggested verbal memory based on the mechanism of recollection. A previous report in sighted noted larger responses for “new” words studied in association with pictures that created a distinctiveness heuristic source factor which enhanced recollection during remembering. Prior behavioral studies in early blind noted an exceptional ability to recall words. Utilization of this skill by participants in the current study possibly engendered recollection that augmented remembering “old” words. A larger response when identifying “new” words possibly resulted from exhaustive recollecting the sensory properties of “old” words in modality appropriate sensory cortices. The uniqueness of a memory role for occipital cortex is in its cross-modal responses to coding tactile properties of Braille. The latter possibly reflects a “sensory echo” that aids recollection. PMID:22251836

  9. Recognition memory for Braille or spoken words: an fMRI study in early blind.

    PubMed

    Burton, Harold; Sinclair, Robert J; Agato, Alvin

    2012-02-15

    We examined cortical activity in early blind during word recognition memory. Nine participants were blind at birth and one by 1.5years. In an event-related design, we studied blood oxygen level-dependent responses to studied ("old") compared to novel ("new") words. Presentation mode was in Braille or spoken. Responses were larger for identified "new" words read with Braille in bilateral lower and higher tier visual areas and primary somatosensory cortex. Responses to spoken "new" words were larger in bilateral primary and accessory auditory cortex. Auditory cortex was unresponsive to Braille words and occipital cortex responded to spoken words but not differentially with "old"/"new" recognition. Left dorsolateral prefrontal cortex had larger responses to "old" words only with Braille. Larger occipital cortex responses to "new" Braille words suggested verbal memory based on the mechanism of recollection. A previous report in sighted noted larger responses for "new" words studied in association with pictures that created a distinctiveness heuristic source factor which enhanced recollection during remembering. Prior behavioral studies in early blind noted an exceptional ability to recall words. Utilization of this skill by participants in the current study possibly engendered recollection that augmented remembering "old" words. A larger response when identifying "new" words possibly resulted from exhaustive recollecting the sensory properties of "old" words in modality appropriate sensory cortices. The uniqueness of a memory role for occipital cortex is in its cross-modal responses to coding tactile properties of Braille. The latter possibly reflects a "sensory echo" that aids recollection. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Repetition Blindness Reveals Differences between the Representations of Manipulable and Nonmanipulable Objects

    ERIC Educational Resources Information Center

    Harris, Irina M.; Murray, Alexandra M.; Hayward, William G.; O'Callaghan, Claire; Andrews, Sally

    2012-01-01

    We used repetition blindness to investigate the nature of the representations underlying identification of manipulable objects. Observers named objects presented in rapid serial visual presentation streams containing either manipulable or nonmanipulable objects. In half the streams, 1 object was repeated. Overall accuracy was lower when streams…

  11. Early allelic selection in maize as revealed by ancient DNA.

    PubMed

    Jaenicke-Després, Viviane; Buckler, Ed S; Smith, Bruce D; Gilbert, M Thomas P; Cooper, Alan; Doebley, John; Pääbo, Svante

    2003-11-14

    Maize was domesticated from teosinte, a wild grass, by approximately 6300 years ago in Mexico. After initial domestication, early farmers continued to select for advantageous morphological and biochemical traits in this important crop. However, the timing and sequence of character selection are, thus far, known only for morphological features discernible in corn cobs. We have analyzed three genes involved in the control of plant architecture, storage protein synthesis, and starch production from archaeological maize samples from Mexico and the southwestern United States. The results reveal that the alleles typical of contemporary maize were present in Mexican maize by 4400 years ago. However, as recently as 2000 years ago, allelic selection at one of the genes may not yet have been complete.

  12. Early Neolithic water wells reveal the world's oldest wood architecture.

    PubMed

    Tegel, Willy; Elburg, Rengert; Hakelberg, Dietrich; Stäuble, Harald; Büntgen, Ulf

    2012-01-01

    The European Neolithization ~6000-4000 BC represents a pivotal change in human history when farming spread and the mobile style of life of the hunter-foragers was superseded by the agrarian culture. Permanent settlement structures and agricultural production systems required fundamental innovations in technology, subsistence, and resource utilization. Motivation, course, and timing of this transformation, however, remain debatable. Here we present annually resolved and absolutely dated dendroarchaeological information from four wooden water wells of the early Neolithic period that were excavated in Eastern Germany. A total of 151 oak timbers preserved in a waterlogged environment were dated between 5469 and 5098 BC and reveal unexpectedly refined carpentry skills. The recently discovered water wells enable for the first time a detailed insight into the earliest wood architecture and display the technological capabilities of humans ~7000 years ago. The timbered well constructions made of old oak trees feature an unopened tree-ring archive from which annually resolved and absolutely dated environmental data can be culled. Our results question the principle of continuous evolutionary development in prehistoric technology, and contradict the common belief that metal was necessary for complex timber constructions. Early Neolithic craftsmanship now suggests that the first farmers were also the first carpenters.

  13. Early Neolithic Water Wells Reveal the World's Oldest Wood Architecture

    PubMed Central

    Tegel, Willy; Elburg, Rengert; Hakelberg, Dietrich; Stäuble, Harald; Büntgen, Ulf

    2012-01-01

    The European Neolithization ∼6000−4000 BC represents a pivotal change in human history when farming spread and the mobile style of life of the hunter-foragers was superseded by the agrarian culture. Permanent settlement structures and agricultural production systems required fundamental innovations in technology, subsistence, and resource utilization. Motivation, course, and timing of this transformation, however, remain debatable. Here we present annually resolved and absolutely dated dendroarchaeological information from four wooden water wells of the early Neolithic period that were excavated in Eastern Germany. A total of 151 oak timbers preserved in a waterlogged environment were dated between 5469 and 5098 BC and reveal unexpectedly refined carpentry skills. The recently discovered water wells enable for the first time a detailed insight into the earliest wood architecture and display the technological capabilities of humans ∼7000 years ago. The timbered well constructions made of old oak trees feature an unopened tree-ring archive from which annually resolved and absolutely dated environmental data can be culled. Our results question the principle of continuous evolutionary development in prehistoric technology, and contradict the common belief that metal was necessary for complex timber constructions. Early Neolithic craftsmanship now suggests that the first farmers were also the first carpenters. PMID:23284685

  14. Right Occipital Cortex Activation Correlates with Superior Odor Processing Performance in the Early Blind

    PubMed Central

    Grandin, Cécile B.; Dricot, Laurence; Plaza, Paula; Lerens, Elodie; Rombaux, Philippe; De Volder, Anne G.

    2013-01-01

    Using functional magnetic resonance imaging (fMRI) in ten early blind humans, we found robust occipital activation during two odor-processing tasks (discrimination or categorization of fruit and flower odors), as well as during control auditory-verbal conditions (discrimination or categorization of fruit and flower names). We also found evidence for reorganization and specialization of the ventral part of the occipital cortex, with dissociation according to stimulus modality: the right fusiform gyrus was most activated during olfactory conditions while part of the left ventral lateral occipital complex showed a preference for auditory-verbal processing. Only little occipital activation was found in sighted subjects, but the same right-olfactory/left-auditory-verbal hemispheric lateralization was found overall in their brain. This difference between the groups was mirrored by superior performance of the blind in various odor-processing tasks. Moreover, the level of right fusiform gyrus activation during the olfactory conditions was highly correlated with individual scores in a variety of odor recognition tests, indicating that the additional occipital activation may play a functional role in odor processing. PMID:23967263

  15. A Functional Neuroimaging Study of Sound Localization: Visual Cortex Activity Predicts Performance in Early-Blind Individuals

    PubMed Central

    Gougoux, Frédéric; Zatorre, Robert J; Lassonde, Maryse; Voss, Patrice

    2005-01-01

    Blind individuals often demonstrate enhanced nonvisual perceptual abilities. However, the neural substrate that underlies this improved performance remains to be fully understood. An earlier behavioral study demonstrated that some early-blind people localize sounds more accurately than sighted controls using monaural cues. In order to investigate the neural basis of these behavioral differences in humans, we carried out functional imaging studies using positron emission tomography and a speaker array that permitted pseudo-free-field presentations within the scanner. During binaural sound localization, a sighted control group showed decreased cerebral blood flow in the occipital lobe, which was not seen in early-blind individuals. During monaural sound localization (one ear plugged), the subgroup of early-blind subjects who were behaviorally superior at sound localization displayed two activation foci in the occipital cortex. This effect was not seen in blind persons who did not have superior monaural sound localization abilities, nor in sighted individuals. The degree of activation of one of these foci was strongly correlated with sound localization accuracy across the entire group of blind subjects. The results show that those blind persons who perform better than sighted persons recruit occipital areas to carry out auditory localization under monaural conditions. We therefore conclude that computations carried out in the occipital cortex specifically underlie the enhanced capacity to use monaural cues. Our findings shed light not only on intermodal compensatory mechanisms, but also on individual differences in these mechanisms and on inhibitory patterns that differ between sighted individuals and those deprived of vision early in life. PMID:15678166

  16. Cognitive and Neuroplasticity Mechanisms by Which Congenital or Early Blindness May Confer a Protective Effect Against Schizophrenia

    PubMed Central

    Silverstein, Steven M.; Wang, Yushi; Keane, Brian P.

    2013-01-01

    Several authors have noted that there are no reported cases of people with schizophrenia who were born blind or who developed blindness shortly after birth, suggesting that congenital or early (C/E) blindness may serve as a protective factor against schizophrenia. By what mechanisms might this effect operate? Here, we hypothesize that C/E blindness offers protection by strengthening cognitive functions whose impairment characterizes schizophrenia, and by constraining cognitive processes that exhibit excessive flexibility in schizophrenia. After briefly summarizing evidence that schizophrenia is fundamentally a cognitive disorder, we review areas of perceptual and cognitive function that are both impaired in the illness and augmented in C/E blindness, as compared to healthy sighted individuals. We next discuss: (1) the role of neuroplasticity in driving these cognitive changes in C/E blindness; (2) evidence that C/E blindness does not confer protective effects against other mental disorders; and (3) evidence that other forms of C/E sensory loss (e.g., deafness) do not reduce the risk of schizophrenia. We conclude by discussing implications of these data for designing cognitive training interventions to reduce schizophrenia-related cognitive impairment, and perhaps to reduce the likelihood of the development of the disorder itself. PMID:23349646

  17. Adaptive Changes in Early and Late Blind: A fMRI Study of Verb Generation to Heard Nouns

    PubMed Central

    BURTON, H.; SNYDER, A. Z.; DIAMOND, J. B.; RAICHLE, M. E.

    2013-01-01

    Literacy for blind people requires learning Braille. Along with others, we have shown that reading Braille activates visual cortex. This includes striate cortex (V1), i.e., banks of calcarine sulcus, and several higher visual areas in lingual, fusiform, cuneus, lateral occipital, inferior temporal, and middle temporal gyri. The spatial extent and magnitude of magnetic resonance (MR) signals in visual cortex is greatest for those who became blind early in life. Individuals who lost sight as adults, and subsequently learned Braille, still exhibited activity in some of the same visual cortex regions, especially V1. These findings suggest these visual cortex regions become adapted to processing tactile information and that this cross-modal neural change might support Braille literacy. Here we tested the alternative hypothesis that these regions directly respond to linguistic aspects of a task. Accordingly, language task performance by blind persons should activate the same visual cortex regions regardless of input modality. Specifically, visual cortex activity in blind people ought to arise during a language task involving heard words. Eight early blind, six late blind, and eight sighted subjects were studied using functional magnetic resonance imaging (fMRI) during covert generation of verbs to heard nouns. The control task was passive listening to indecipherable sounds (reverse words) matched to the nouns in sound intensity, duration, and spectral content. Functional responses were analyzed at the level of individual subjects using methods based on the general linear model and at the group level, using voxel based ANOVA and t-test analyses. Blind and sighted subjects showed comparable activation of language areas in left inferior frontal, dorsolateral prefrontal, and left posterior superior temporal gyri. The main distinction was bilateral, left dominant activation of the same visual cortex regions previously noted with Braille reading in all blind subjects. The

  18. Early cessation of triptorelin in in vitro fertilization: a double-blind, randomized study.

    PubMed

    Simons, Arnold H M; Roelofs, Henny J M; Schmoutziguer, Alex P E; Roozenburg, Brigitte J; van't Hof-van den Brink, Eefje P; Schoonderwoerd, Simon A

    2005-04-01

    To compare the efficacy of two early cessation protocols of triptorelin treatment in controlled ovarian hyperstimulation with the conventional long protocol in in vitro fertilization/intracytoplasmic sperm injection. A double-blind, randomized, multicenter study. Three Dutch hospitals. One hundred seventy-eight women randomized to one of three treatment groups at the start of stimulation. Midluteally started triptorelin administration was continued until the first day of hMG treatment (group S), or up to and including the fourth day of hMG treatment (group M) or the day of hCG injection (group L). Occurrence of a premature LH surge. One premature LH surge was observed in group M but not in groups S and L. Both early cessation protocols (S and M) are at least as effective as the long protocol (L) with regard to the number of oocytes (11.1 and 10.3 vs. 9.3), number of embryos (7.3 and 6.5 vs. 5.5), and ongoing pregnancy rate (28% and 24% vs. 21%). Early cessation of triptorelin on day 1 of hMG treatment in a midluteally started IVF protocol is as effective as the traditional long protocol in preventing a premature LH surge and results in similar fertility effects.

  19. Tactile Object Familiarity in the Blind Brain Reveals the Supramodal Perceptual-Mnemonic Nature of the Perirhinal Cortex

    PubMed Central

    Cacciamani, Laura; Likova, Lora T.

    2016-01-01

    This study is the first to investigate the neural underpinnings of tactile object familiarity in the blind during both perception and memory. In the sighted, the perirhinal cortex (PRC) has been implicated in the assessment of visual object familiarity—a crucial everyday task—as evidenced by reduced activation when an object becomes familiar. Here, to examine the PRC’s role in tactile object familiarity in the absence of vision, we trained blind participants on a unique memory-guided drawing technique and measured brain activity while they perceptually explored raised-line drawings, drew them from tactile memory, and scribbled (control). Functional magnetic resonance imaging (fMRI) before and after a week of training revealed a significant decrease in PRC activation from pre- to post-training (i.e., from unfamiliar to familiar) during perceptual exploration as well as memory-guided drawing, but not scribbling. This familiarity-based reduction is the first evidence that the PRC represents tactile object familiarity in the blind. Furthermore, the finding of this effect during both tactile perception and tactile memory provides the critical link in establishing the PRC as a structure whose representations are supramodal for both perception and memory. PMID:27148002

  20. Double-Blind Maintenance Safety and Effectiveness Findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

    ERIC Educational Resources Information Center

    Findling, Robert L.; Johnson, Jacqueline L.; McClellan, Jon; Frazier, Jean A.; Vitiello, Benedetto; Hamer, Robert M.; Lieberman, Jeffrey A.; Ritz, Louise; McNamara, Nora K.; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E.; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

    2010-01-01

    Objective: To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Method: Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication…

  1. Development and Validation of the Self-Acceptance Scale for Persons with Early Blindness: The SAS-EB

    PubMed Central

    Morgado, Fabiane Frota da Rocha; Campana, Angela Nogueira Neves Betanho; Tavares, Maria da Consolação Gomes Cunha Fernandes

    2014-01-01

    Investigations of self-acceptance are critical to understanding the development and maintenance of psychological health. However, valid and reliable instruments for measuring self-acceptance in persons with early blindness have yet to be developed. The current research describes three studies designed to develop and validate the Self-acceptance Scale for Persons with Early Blindness (SAS-EB). In Study 1, we developed the initial item pool. Thirty-three items were generated, based on data from specialized literature and from 2 focus groups. Items were organized in a three-factor structure, theoretically predicted for SAS-EB - (1) body acceptance, (2) self-protection from social stigmas, and (3) feeling and believing in one's capacities. In Study 2, information obtained from a panel of 9 experts and 22 persons with early blindness representing the target population was used to refine the initial item pool, generating a new pool of 27 items. In Study 3, 318 persons with early blindness (141 women and 177 men), between 18 and 60 years of age (M = 37.74 years, SD = 12.37) answered the new pool of 27 items. After the elimination of 9 items using confirmatory factor analysis, we confirmed the theoretical three-factor structure of the SAS-EB. Study 3 also provided support for the scale's internal consistency and construct validity. Finally, the psychometric properties of the SAS-EB, its utility, and its limitations are discussed along with considerations for future research. PMID:25268633

  2. Double-blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson's disease patients.

    PubMed

    Stern, Matthew B; Marek, Kenneth L; Friedman, Joseph; Hauser, Robert A; LeWitt, Peter A; Tarsy, Daniel; Olanow, C Warren

    2004-08-01

    Rasagiline (N-propargyl-1(R)-aminoindan) mesylate is a potent, selective, and irreversible monoamine oxidase-B inhibitor. This study was designed to evaluate the safety, tolerability, and preliminary efficacy of rasagiline monotherapy in early Parkinson's disease (PD) patients not receiving levodopa. The study was performed as a multicenter, parallel-group, double-blind, randomized, placebo-controlled, 10-week study. Fifty-six PD patients were randomly assigned to rasagiline mesylate 1, 2, or 4 mg once daily, or placebo. A 3-week dose-escalation period was followed by a 7-week maintenance phase. At week 10, the mean (+/-SE) changes from baseline in total Unified Parkinson's Disease Rating Scale (UPDRS) score were -1.8 (+/-1.3), -3.6 (+/-1.7), -3.6 (+/-1.2), and -0.5 (+/-0.8) in the rasagiline 1, 2, and 4 mg/day and placebo groups, respectively. Analysis of responders showed that 28% of patients (12 of 43) receiving rasagiline had an improvement in total UPDRS score of greater than 30%, compared with none of the patients receiving placebo (P < 0.05, Fisher's exact test). The frequency and types of adverse events reported by rasagiline-treated and placebo-treated patients were similar. These results suggest that rasagiline monotherapy is well tolerated and efficacious in early PD. Copyright 2004 Movement Disorder Society

  3. Transdermal rotigotine in early stage Parkinson's disease: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Mizuno, Yoshikuni; Nomoto, Masahiro; Kondo, Tomoyoshi; Hasegawa, Kazuko; Murata, Miho; Takeuchi, Masahiro; Ikeda, Junji; Tomida, Takayuki; Hattori, Nobutaka

    2013-09-01

    We conducted a randomized, double-blind, placebo-controlled trial to determine the safety and efficacy of transdermal rotigotine at doses up to 16 mg/24 hours in patients with early stage Parkinson's disease (PD) in Japan. Patients received once-daily rotigotine 2 to 16 mg/24 hours (mean dose, 12.8 mg/24 hours; n = 82) or placebo (n = 90) for 12 weeks. The primary endpoint was the change in Unified Parkinson's Disease Rating Scale (UPDRS) part II (activities of daily living) and part III (motor function) scores from baseline to the end of treatment. The mean (± standard deviation) changes in UPDRS part II and III scores were -8.4 ± 9.7 in the rotigotine group and -4.1 ± 8.2 in the placebo group and were significantly different (P = 0.002). More patients in the rotigotine group than in the placebo group had a ≥ 20% score reduction. No serious drug-related adverse events were reported. Rotigotine at doses up to 16 mg/24 hours was well tolerated and improved function in patients with early stage PD. © 2013 International Parkinson and Movement Disorder Society.

  4. Blind Astronomers

    NASA Astrophysics Data System (ADS)

    Hockey, Thomas A.

    2011-01-01

    The phrase "blind astronomer” is used as an allegorical oxymoron. However, there were and are blind astronomers. What of famous blind astronomers? First, it must be stated that these astronomers were not martyrs to their craft. It is a myth that astronomers blind themselves by observing the Sun. As early as France's William of Saint-Cloud (circa 1290) astronomers knew that staring at the Sun was ill-advised and avoided it. Galileo Galilei did not invent the astronomical telescope and then proceed to blind himself with one. Galileo observed the Sun near sunrise and sunset or through projection. More than two decades later he became blind, as many septuagenarians do, unrelated to their profession. Even Isaac Newton temporarily blinded himself, staring at the reflection of the Sun when he was a twentysomething. But permanent Sun-induced blindness? No, it did not happen. For instance, it was a stroke that left Scotland's James Gregory (1638-1675) blind. (You will remember the Gregorian telescope.) However, he died days later. Thus, blindness little interfered with his occupation. English Abbot Richard of Wallingford (circa 1291 - circa 1335) wrote astronomical works and designed astronomical instruments. He was also blind in one eye. Yet as he further suffered from leprosy, his blindness seems the lesser of Richard's maladies. Perhaps the most famous professionally active, blind astronomer (or almost blind astronomer) is Dominique-Francois Arago (1786-1853), director until his death of the powerful nineteenth-century Paris Observatory. I will share other _ some poignant _ examples such as: William Campbell, whose blindness drove him to suicide; Leonhard Euler, astronomy's Beethoven, who did nearly half of his life's work while almost totally blind; and Edwin Frost, who "observed” a total solar eclipse while completely sightless.

  5. Effects of Febuxostat in Early Gout: A Randomized, Double-Blind, Placebo-Controlled Study.

    PubMed

    Dalbeth, Nicola; Saag, Kenneth G; Palmer, William E; Choi, Hyon K; Hunt, Barbara; MacDonald, Patricia A; Thienel, Ulrich; Gunawardhana, Lhanoo

    2017-12-01

    To assess the effect of treatment with febuxostat versus placebo on joint damage in hyperuricemic subjects with early gout (1 or 2 gout flares). In this double-blind, placebo-controlled study, 314 subjects with hyperuricemia (serum uric acid [UA] level of ≥7.0 mg/dl) and early gout were randomized 1:1 to receive once-daily febuxostat 40 mg (increased to 80 mg if the serum UA level was ≥6.0 mg/dl on day 14) or placebo. The primary efficacy end point was the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint. Additional efficacy end points included change from baseline to month 24 in the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) scores for synovitis, erosion, and edema in the single affected joint, the incidence of gout flares, and serum UA levels. Safety was assessed throughout the study. Treatment with febuxostat did not lead to any notable changes in joint erosion over 2 years. In both treatment groups, the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint was minimal, with no between-group differences. However, treatment with febuxostat significantly improved the RAMRIS synovitis score at month 24 compared with placebo treatment (change from baseline -0.43 versus -0.07; P <0.001), decreased the overall incidence of gout flares (29.3% versus 41.4%; P < 0.05), and improved serum UA control (62.8% versus 5.7%; P < 0.001). No major safety concerns were reported. Urate-lowering therapy with febuxostat improved magnetic resonance imaging-determined synovitis and reduced the incidence of gout flares in subjects with early gout. © 2017 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

  6. Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

    PubMed Central

    Wahner-Roedler, Dietlind L.; Thompson, Jeffrey M.; Luedtke, Connie A.; King, Susan M.; Cha, Stephen S.; Elkin, Peter L.; Bruce, Barbara K.; Townsend, Cynthia O.; Bergeson, Jody R.; Eickhoff, Andrea L.; Loehrer, Laura L.; Sood, Amit; Bauer, Brent A.

    2011-01-01

    Most patients with fibromyalgia use complementary and alternative medicine (CAM). Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein) shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ) and the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02) and by 18% in the placebo group (P < .001). The difference in change in scores between the groups was not significant (P = .16). With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004) and in the placebo group by 15% (P = .05). The change in scores was similar in the groups (P = .83). Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control) shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated. PMID:18990724

  7. Activation of the occipital cortex and deactivation of the default mode network during working memory in the early blind.

    PubMed

    Park, Hae-Jeong; Chun, Ji-Won; Park, Bumhee; Park, Haeil; Kim, Joong Il; Lee, Jong Doo; Kim, Jae-Jin

    2011-05-01

    Although blind people heavily depend on working memory to manage daily life without visual information, it is not clear yet whether their working memory processing involves functional reorganization of the memory-related cortical network. To explore functional reorganization of the cortical network that supports various types of working memory processes in the early blind, we investigated activation differences between 2-back tasks and 0-back tasks using fMRI in 10 congenitally blind subjects and 10 sighted subjects. We used three types of stimulus sequences: words for a verbal task, pitches for a non-verbal task, and sound locations for a spatial task. When compared to the sighted, the blind showed additional activations in the occipital lobe for all types of stimulus sequences for working memory and more significant deactivation in the posterior cingulate cortex of the default mode network. The blind had increased effective connectivity from the default mode network to the left parieto-frontal network and from the occipital cortex to the right parieto-frontal network during the 2-back tasks than the 0-back tasks. These findings suggest not only cortical plasticity of the occipital cortex but also reorganization of the cortical network for the executive control of working memory.

  8. Toys for Early Development of the Young Blind Child: A Guide for Parents.

    ERIC Educational Resources Information Center

    Illinois State Office of the Superintendent of Public Instruction, Springfield.

    A booklet is presented for parents of blind children. This booklet lists various toys that are useful for the child in his development and cognitive growth. Three kits of toys are presented. Each of these kits was developed for children of approximate age groups. Kit #1 is for the very young blind infants and contains toys that usually interest…

  9. Euryhaline ecology of early tetrapods revealed by stable isotopes.

    PubMed

    Goedert, Jean; Lécuyer, Christophe; Amiot, Romain; Arnaud-Godet, Florent; Wang, Xu; Cui, Linlin; Cuny, Gilles; Douay, Guillaume; Fourel, François; Panczer, Gérard; Simon, Laurent; Steyer, J-Sébastien; Zhu, Min

    2018-06-01

    The fish-to-tetrapod transition-followed later by terrestrialization-represented a major step in vertebrate evolution that gave rise to a successful clade that today contains more than 30,000 tetrapod species. The early tetrapod Ichthyostega was discovered in 1929 in the Devonian Old Red Sandstone sediments of East Greenland (dated to approximately 365 million years ago). Since then, our understanding of the fish-to-tetrapod transition has increased considerably, owing to the discovery of additional Devonian taxa that represent early tetrapods or groups evolutionarily close to them. However, the aquatic environment of early tetrapods and the vertebrate fauna associated with them has remained elusive and highly debated. Here we use a multi-stable isotope approach (δ 13 C, δ 18 O and δ 34 S) to show that some Devonian vertebrates, including early tetrapods, were euryhaline and inhabited transitional aquatic environments subject to high-magnitude, rapid changes in salinity, such as estuaries or deltas. Euryhalinity may have predisposed the early tetrapod clade to be able to survive Late Devonian biotic crises and then successfully colonize terrestrial environments.

  10. Tactile Acuity in the Blind: A Closer Look Reveals Superiority over the Sighted in Some but Not All Cutaneous Tasks

    ERIC Educational Resources Information Center

    Alary, Flamine; Duquette, Marco; Goldstein, Rachel; Chapman, C. Elaine; Voss, Patrice; La Buissonniere-Ariza, Valerie; Lepore, Franco

    2009-01-01

    Previous studies have shown that blind subjects may outperform the sighted on certain tactile discrimination tasks. We recently showed that blind subjects outperformed the sighted in a haptic 2D-angle discrimination task. The purpose of this study was to compare the performance of the same blind (n = 16) and sighted (n = 17, G1) subjects in three…

  11. Early visual experience and the recognition of basic facial expressions: involvement of the middle temporal and inferior frontal gyri during haptic identification by the early blind

    PubMed Central

    Kitada, Ryo; Okamoto, Yuko; Sasaki, Akihiro T.; Kochiyama, Takanori; Miyahara, Motohide; Lederman, Susan J.; Sadato, Norihiro

    2012-01-01

    Face perception is critical for social communication. Given its fundamental importance in the course of evolution, the innate neural mechanisms can anticipate the computations necessary for representing faces. However, the effect of visual deprivation on the formation of neural mechanisms that underlie face perception is largely unknown. We previously showed that sighted individuals can recognize basic facial expressions by haptics surprisingly well. Moreover, the inferior frontal gyrus (IFG) and posterior superior temporal sulcus (pSTS) in the sighted subjects are involved in haptic and visual recognition of facial expressions. Here, we conducted both psychophysical and functional magnetic-resonance imaging (fMRI) experiments to determine the nature of the neural representation that subserves the recognition of basic facial expressions in early blind individuals. In a psychophysical experiment, both early blind and sighted subjects haptically identified basic facial expressions at levels well above chance. In the subsequent fMRI experiment, both groups haptically identified facial expressions and shoe types (control). The sighted subjects then completed the same task visually. Within brain regions activated by the visual and haptic identification of facial expressions (relative to that of shoes) in the sighted group, corresponding haptic identification in the early blind activated regions in the inferior frontal and middle temporal gyri. These results suggest that the neural system that underlies the recognition of basic facial expressions develops supramodally even in the absence of early visual experience. PMID:23372547

  12. Early visual experience and the recognition of basic facial expressions: involvement of the middle temporal and inferior frontal gyri during haptic identification by the early blind.

    PubMed

    Kitada, Ryo; Okamoto, Yuko; Sasaki, Akihiro T; Kochiyama, Takanori; Miyahara, Motohide; Lederman, Susan J; Sadato, Norihiro

    2013-01-01

    Face perception is critical for social communication. Given its fundamental importance in the course of evolution, the innate neural mechanisms can anticipate the computations necessary for representing faces. However, the effect of visual deprivation on the formation of neural mechanisms that underlie face perception is largely unknown. We previously showed that sighted individuals can recognize basic facial expressions by haptics surprisingly well. Moreover, the inferior frontal gyrus (IFG) and posterior superior temporal sulcus (pSTS) in the sighted subjects are involved in haptic and visual recognition of facial expressions. Here, we conducted both psychophysical and functional magnetic-resonance imaging (fMRI) experiments to determine the nature of the neural representation that subserves the recognition of basic facial expressions in early blind individuals. In a psychophysical experiment, both early blind and sighted subjects haptically identified basic facial expressions at levels well above chance. In the subsequent fMRI experiment, both groups haptically identified facial expressions and shoe types (control). The sighted subjects then completed the same task visually. Within brain regions activated by the visual and haptic identification of facial expressions (relative to that of shoes) in the sighted group, corresponding haptic identification in the early blind activated regions in the inferior frontal and middle temporal gyri. These results suggest that the neural system that underlies the recognition of basic facial expressions develops supramodally even in the absence of early visual experience.

  13. Blocks Are Educational: Revealing Discourses through Early Childhood Policy Illustrations

    ERIC Educational Resources Information Center

    Manning, Suzanne

    2018-01-01

    In the course of a study on the impacts of changing early childhood policy in Aotearoa New Zealand since 1989, the illustrations accompanying three major government reports and policies stood out as encapsulating the changes in underlying discourses. This enabled the illustrations from these three policy reports to be used for a historical…

  14. A Blind Circadian Clock in Cavefish Reveals that Opsins Mediate Peripheral Clock Photoreception

    PubMed Central

    Cavallari, Nicola; Frigato, Elena; Vallone, Daniela; Fröhlich, Nadine; Lopez-Olmeda, Jose Fernando; Foà, Augusto; Berti, Roberto; Sánchez-Vázquez, Francisco Javier; Bertolucci, Cristiano; Foulkes, Nicholas S.

    2011-01-01

    The circadian clock is synchronized with the day-night cycle primarily by light. Fish represent fascinating models for deciphering the light input pathway to the vertebrate clock since fish cell clocks are regulated by direct light exposure. Here we have performed a comparative, functional analysis of the circadian clock involving the zebrafish that is normally exposed to the day-night cycle and a cavefish species that has evolved in perpetual darkness. Our results reveal that the cavefish retains a food-entrainable clock that oscillates with an infradian period. Importantly, however, this clock is not regulated by light. This comparative study pinpoints the two extra-retinal photoreceptors Melanopsin (Opn4m2) and TMT-opsin as essential upstream elements of the peripheral clock light input pathway. PMID:21909239

  15. Ancient European dog genomes reveal continuity since the Early Neolithic

    PubMed Central

    Botigué, Laura R.; Song, Shiya; Scheu, Amelie; Gopalan, Shyamalika; Pendleton, Amanda L.; Oetjens, Matthew; Taravella, Angela M.; Seregély, Timo; Zeeb-Lanz, Andrea; Arbogast, Rose-Marie; Bobo, Dean; Daly, Kevin; Unterländer, Martina; Burger, Joachim; Kidd, Jeffrey M.; Veeramah, Krishna R.

    2017-01-01

    Europe has played a major role in dog evolution, harbouring the oldest uncontested Palaeolithic remains and having been the centre of modern dog breed creation. Here we sequence the genomes of an Early and End Neolithic dog from Germany, including a sample associated with an early European farming community. Both dogs demonstrate continuity with each other and predominantly share ancestry with modern European dogs, contradicting a previously suggested Late Neolithic population replacement. We find no genetic evidence to support the recent hypothesis proposing dual origins of dog domestication. By calibrating the mutation rate using our oldest dog, we narrow the timing of dog domestication to 20,000–40,000 years ago. Interestingly, we do not observe the extreme copy number expansion of the AMY2B gene characteristic of modern dogs that has previously been proposed as an adaptation to a starch-rich diet driven by the widespread adoption of agriculture in the Neolithic. PMID:28719574

  16. The Blind Child and His Parents: Congenital Visual Defect and the Repercussion of Family Attitudes on the Early Development of the Child.

    ERIC Educational Resources Information Center

    Lairy, G. C.; Harrison-Covello, A.

    Discussed are the effects of parental attitudes on the early development of the congenitally blind child. The disproportion between family reactions and the limitations of the handicap are attributed to symbolic aspects of blindness and previously existing pathological elements in the parents. Compared are developmental milestones (such as the…

  17. Metamorphic sole formation reveals plate interface rheology during early subduction

    NASA Astrophysics Data System (ADS)

    Mathieu, S.; Agard, P.; Dubacq, B.; Plunder, A.; Prigent, C.

    2015-12-01

    Metamorphic soles are m to ~500m thick tectonic slices welded beneath most large ophiolites. They correspond to highly to mildly deformed portions of oceanic lithosphere metamorphosed at amphibolite to granulite facies peak conditions. Metamorphic soles are interpreted as formed ≤1-2Ma after intraoceanic subduction initiation by heat transfer from the hot, incipient mantle wegde to the underthrusting lower plate. Their early accretion and exhumation together with the future ophiolite implies at least one jump of the subduction plate interface from above to below the metamorphic sole. Metamorphic soles thus represent one of the few remnants of the very early evolution of the subduction plate interface and provide major constraints on the thermal structure and the effective rheology of the crust and mantle along the nascent slab interface.We herein present a structural and petrological detailed description of the Oman and Turkey metamorphic soles. Both soles present a steep inverted metamorphic structure, with isograds subparallel to the peridotite contact, in which the proportion of mafic rocks, pressure and temperature conditions increase upward. They comprise, as most metamorphic soles worldwide, two main units: (1) a high-grade unit adjacent to the overlying peridotite composed of granulitized to amphibolized metabasalts, with rare metasedimentary interlayers (~800±100ºC at 10±2kbar) and (2) a low-grade greenschist facies unit composed of metasedimentary rocks with rare metatuffs (~500±100ºC at 5±2kbar). We provide for the first time refined P-T peak condition estimations by means of pseudosection modelling and maximum temperature constraints for the Oman low-grade sole by RAMAN thermometry. In order to quantify micro-scale deformations trough the sole, we also present EBSD data on the Oman garnet-bearing and garnet-free high-grade sole.With these new constraints, we finally propose a new conceptual mechanical model for metamorphic sole formation. This

  18. Early MAVEN Deep Dip campaign reveals thermosphere and ionosphere variability.

    PubMed

    Bougher, S; Jakosky, B; Halekas, J; Grebowsky, J; Luhmann, J; Mahaffy, P; Connerney, J; Eparvier, F; Ergun, R; Larson, D; McFadden, J; Mitchell, D; Schneider, N; Zurek, R; Mazelle, C; Andersson, L; Andrews, D; Baird, D; Baker, D N; Bell, J M; Benna, M; Brain, D; Chaffin, M; Chamberlin, P; Chaufray, J-Y; Clarke, J; Collinson, G; Combi, M; Crary, F; Cravens, T; Crismani, M; Curry, S; Curtis, D; Deighan, J; Delory, G; Dewey, R; DiBraccio, G; Dong, C; Dong, Y; Dunn, P; Elrod, M; England, S; Eriksson, A; Espley, J; Evans, S; Fang, X; Fillingim, M; Fortier, K; Fowler, C M; Fox, J; Gröller, H; Guzewich, S; Hara, T; Harada, Y; Holsclaw, G; Jain, S K; Jolitz, R; Leblanc, F; Lee, C O; Lee, Y; Lefevre, F; Lillis, R; Livi, R; Lo, D; Ma, Y; Mayyasi, M; McClintock, W; McEnulty, T; Modolo, R; Montmessin, F; Morooka, M; Nagy, A; Olsen, K; Peterson, W; Rahmati, A; Ruhunusiri, S; Russell, C T; Sakai, S; Sauvaud, J-A; Seki, K; Steckiewicz, M; Stevens, M; Stewart, A I F; Stiepen, A; Stone, S; Tenishev, V; Thiemann, E; Tolson, R; Toublanc, D; Vogt, M; Weber, T; Withers, P; Woods, T; Yelle, R

    2015-11-06

    The Mars Atmosphere and Volatile Evolution (MAVEN) mission, during the second of its Deep Dip campaigns, made comprehensive measurements of martian thermosphere and ionosphere composition, structure, and variability at altitudes down to ~130 kilometers in the subsolar region. This altitude range contains the diffusively separated upper atmosphere just above the well-mixed atmosphere, the layer of peak extreme ultraviolet heating and primary reservoir for atmospheric escape. In situ measurements of the upper atmosphere reveal previously unmeasured populations of neutral and charged particles, the homopause altitude at approximately 130 kilometers, and an unexpected level of variability both on an orbit-to-orbit basis and within individual orbits. These observations help constrain volatile escape processes controlled by thermosphere and ionosphere structure and variability. Copyright © 2015, American Association for the Advancement of Science.

  19. Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial

    PubMed Central

    2015-01-01

    Summary Background A systematic assessment of potential disease-modifying compounds for Parkinson's disease concluded that pioglitazone could hold promise for the treatment of patients with this disease. We assessed the effect of pioglitazone on the progression of Parkinson's disease in a multicentre, double-blind, placebo-controlled, futility clinical trial. Methods Participants with the diagnosis of early Parkinson's disease on a stable regimen of 1 mg/day rasagiline or 10 mg/day selegiline were randomly assigned (1:1:1) to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo. Investigators were masked to the treatment assignment. Only the statistical centre and the central pharmacy knew the treatment name associated with the randomisation number. The primary outcome was the change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score between the baseline and 44 weeks, analysed by intention to treat. The primary null hypothesis for each dose group was that the mean change in UPDRS was 3 points less than the mean change in the placebo group. The alternative hypothesis (of futility) was that pioglitazone is not meaningfully different from placebo. We rejected the null if there was significant evidence of futility at the one-sided alpha level of 0.10. The study is registered at ClinicalTrials.gov, number NCT01280123. Findings 210 patients from 35 sites in the USA were enrolled between May 10, 2011, and July 31, 2013. The primary analysis included 72 patients in the 15 mg group, 67 in the 45 mg group, and 71 in the placebo group. The mean total UPDRS change at 44 weeks was 4.42 (95% CI 2.55–6.28) for 15 mg pioglitazone, 5.13 (95% CI 3.17–7.08) for 45 mg pioglitazone, and 6.25 (95% CI 4.35–8.15) for placebo (higher change scores are worse). The mean difference between the 15 mg and placebo groups was −1.83 (80% CI −3.56 to −0.10) and the null hypothesis could not be rejected (p=0.19). The mean difference between the 45 mg and placebo

  20. Oman metamorphic sole formation reveals early subduction dynamics

    NASA Astrophysics Data System (ADS)

    Soret, Mathieu; Agard, Philippe; Dubacq, Benoît; Plunder, Alexis; Ildefonse, Benoît; Yamato, Philippe; Prigent, Cécile

    2016-04-01

    Metamorphic soles correspond to m to ~500m thick tectonic slices welded beneath most of the large-scale ophiolites. They typically show a steep inverted metamorphic structure where the pressure and temperature conditions of crystallization increase upward (from 500±100°C at 0.5±0.2 GPa to 800±100°C at 1.0±0.2 GPa), with isograds subparallel to the contact with the overlying ophiolitic peridotite. The proportion of mafic rocks in metamorphic soles also increases from the bottom (meta-sediments rich) to the top (approaching the ophiolite peridotites). These soles are interpreted as the result of heat transfer from the incipient mantle wedge toward the nascent slab (associated with large-scale fluid transfer and possible shear heating) during the first My of intra-oceanic subduction (as indicated by radiometric ages). Metamorphic soles provide therefore major constraints on early subduction dynamics (i.e., thermal structure, fluid migration and rheology along the nascent slab interface). We present a detailed structural and petrological study of the metamorphic sole from 4 major cross-sections along the Oman ophiolite. We show precise pressure-temperature estimates obtained by pseudosection modelling and EBSD measurements performed on both the garnet-bearing and garnet-free high-grade sole. Results allow quantification of the micro-scale deformation and highlight differences in pressure-temperature-deformation conditions between the 4 different locations, showing that the inverted metamorphic gradient through the sole is not continuous in all locations. Based on these new constraints, we suggest a new tectonic-petrological model for the formation of metamorphic soles below ophiolites. This model involves the stacking of several homogeneous slivers of oceanic crust leading to the present-day structure of the sole. In this view, these thrusts are the result of rheological contrasts between the sole and the peridotite as the plate interface progressively cools down

  1. Signs of Early-stage Disk Growth Revealed with ALMA

    NASA Astrophysics Data System (ADS)

    Yen, Hsi-Wei; Koch, Patrick M.; Takakuwa, Shigehisa; Krasnopolsky, Ruben; Ohashi, Nagayoshi; Aso, Yusuke

    2017-01-01

    We present ALMA 1.3 mm continuum, 12CO, C18O, and SO data for the Class 0 protostars Lupus 3 MMS, IRAS 15398-3559, and IRAS 16253-2429 at resolutions of ˜100 au. By measuring a rotational profile in C18O, a 100 au Keplerian disk around a 0.3 M⊙ protostar is observed in Lupus 3 MMS. No 100 au Keplerian disks are observed in IRAS 15398-3559 and IRAS 16253-2429. Nevertheless, embedded compact (<30 au) continuum components are detected. The C18O emission in IRAS 15398-3559 shows signatures of infall with a constant angular momentum. IRAS 16253-2429 exhibits signatures of infall and rotation, but its rotational profile is unresolved. By fitting the C18O data with our kinematic models, the protostellar masses and the disk radii are inferred to be 0.01 M⊙ and 20 au in IRAS 15398-3559, and 0.03 M⊙ and 6 au in IRAS 16253-2429. By comparing the specific angular momentum profiles from 10,000 au to 100 au in eight Class 0 and I protostars, we find that the evolution of envelope rotation can be described with conventional inside-out collapse models. In comparison with a sample of 18 protostars with known disk radii, our results reveal signs of disk growth, with the disk radius increasing as {{M}* }0.8+/- 0.14 or {t}1.09+/- 0.37 in the Class 0 stage, where M* is the protostellar mass and t is the age. The disk growth rate slows down in the Class I stage. In addition, we find a hint that the mass accretion rate declines as {t}-0.26+/- 0.04 from the Class 0 to the Class I stages.

  2. Acute rejection characteristics from a prospective, randomized, double-blind, placebo-controlled multicenter trial of early corticosteroid withdrawal.

    PubMed

    Gaber, A Osama; Moore, Linda W; Alloway, Rita R; Woodle, E Steve; Pirsch, John; Shihab, Fuad; Henning, Alice; Fitzsimmons, William; Holman, John; Reisfield, Robin; First, M Roy

    2013-02-27

    This report characterizes acute rejection and rejection outcomes in subjects randomized to continuous corticosteroid therapy (CCS) or early corticosteroid withdrawal (CSWD; 7 days after transplantation) in the Astellas Blinded CSWD Trial. The Astellas Blinded CSWD Trial was a 5-year, prospective, multicenter, randomized, double-blind trial of early CCS withdrawal in 386 kidney transplant recipients (195 CCS and 191 CSWD). Tacrolimus and mycophenolate mofetil were required as well as either rabbit antithymocyte globulin or interleukin-2 receptor antibody induction. Biopsy-confirmed acute rejection (BCAR) was grade 1A or higher by Banff criteria. This report also provides borderline changes (BL) that did not meet Banff grade 1A included with BCAR (BCAR+BL). BCAR+BL was 25 (12.8%) in CCS group and 42 (22.0%) in CSWD group (P=0.022). Early BCAR+BL (first 90 days after transplantation) was less frequent in CCS (n=5 [2.6%]) than in CSWD (n=22 [11.5%]; P<0.001). Among non-African-American subjects, early BCAR+BL occurred more often in CSWD (n=20 [12.7%]) versus CCS (n=2 [1.3%]; P<0.001). Late acute rejection (>2 years) occurred more often in African-American subjects in CCS (n=5 [13.9%]) than in CSWD (n=0; P=0.056). Risk factors were CSWD (hazard ratio [HR], 4.72; P<0.002) and human leukocyte antigen mismatch (HR, 1.48; P<0.005) for early BCAR+BL and CSWD (HR, 1.9; P<0.02), human leukocyte antigen mismatch (HR, 1.2; P<0.01), and age (HR, 0.97; P<0.002) for 5-year rejection. The HR for graft loss associated with BCAR+BL was 8.8. BCAR+BL may occur more frequently during the early period after transplantation under an early CSWD regimen with tacrolimus plus induction compared with CCS, particularly among non-African-Americans.

  3. Early Visual Deprivation Severely Compromises the Auditory Sense of Space in Congenitally Blind Children

    ERIC Educational Resources Information Center

    Vercillo, Tiziana; Burr, David; Gori, Monica

    2016-01-01

    A recent study has shown that congenitally blind adults, who have never had visual experience, are impaired on an auditory spatial bisection task (Gori, Sandini, Martinoli, & Burr, 2014). In this study we investigated how thresholds for auditory spatial bisection and auditory discrimination develop with age in sighted and congenitally blind…

  4. The reconnaissance and early-warning optical system design for dual field of space-based "solar blind ultraviolet"

    NASA Astrophysics Data System (ADS)

    Wang, Wen-cong; Jin, Dong-dong; Shao, Fei; Hu, Hui-jun; Shi, Yu-feng; Song, Juan; Zhang, Yu-tu; Yong, Liu

    2016-07-01

    With the development of modern technology, especially the development of information technology at high speed, the ultraviolet early warning system plays an increasingly important role. In the modern warfare, how to detect the threats earlier, prevent and reduce the attack of precision-guided missile has become a new challenge. Because the ultraviolet warning technology has high environmental adaptability, the low false alarm rate, small volume and other advantages, in the military field applications it has been developed rapidly. According to current application demands for solar blind ultraviolet detection and warning, this paper proposes a reconnaissance and early-warning optical system, which covers solar blind ultraviolet (250nm-280nm) and dual field. This structure takes advantage of a narrow field of view and long focal length optical system to achieve the target object detection, uses wide-field and short focal length optical system to achieve early warning of the target object. It makes use of an ultraviolet beam-splitter to achieve the separation of two optical systems. According to the detector and the corresponding application needs of two visual field of the optical system, the calculation and optical system design were completed. After the design, the MTF of the two optical system is more than 0.8@39lp/mm. A single pixel energy concentration is greater than 80%.

  5. Early prediction of coma recovery after cardiac arrest with blinded pupillometry.

    PubMed

    Solari, Daria; Rossetti, Andrea O; Carteron, Laurent; Miroz, John-Paul; Novy, Jan; Eckert, Philippe; Oddo, Mauro

    2017-06-01

    Prognostication studies on comatose cardiac arrest (CA) patients are limited by lack of blinding, potentially causing overestimation of outcome predictors and self-fulfilling prophecy. Using a blinded approach, we analyzed the value of quantitative automated pupillometry to predict neurological recovery after CA. We examined a prospective cohort of 103 comatose adult patients who were unconscious 48 hours after CA and underwent repeated measurements of quantitative pupillary light reflex (PLR) using the Neurolight-Algiscan device. Clinical examination, electroencephalography (EEG), somatosensory evoked potentials (SSEP), and serum neuron-specific enolase were performed in parallel, as part of standard multimodal assessment. Automated pupillometry results were blinded to clinicians involved in patient care. Cerebral Performance Categories (CPC) at 1 year was the outcome endpoint. Survivors (n = 50 patients; 32 CPC 1, 16 CPC 2, 2 CPC 3) had higher quantitative PLR (median = 20 [range = 13-41] vs 11 [0-55] %, p < 0.0001) and constriction velocity (1.46 [0.85-4.63] vs 0.94 [0.16-4.97] mm/s, p < 0.0001) than nonsurvivors. At 48 hours, a quantitative PLR < 13% had 100% specificity and positive predictive value to predict poor recovery (0% false-positive rate), and provided equal performance to that of EEG and SSEP. Reduced quantitative PLR correlated with higher serum neuron-specific enolase (Spearman r = -0.52, p < 0.0001). Reduced quantitative PLR correlates with postanoxic brain injury and, when compared to standard multimodal assessment, is highly accurate in predicting long-term prognosis after CA. This is the first prognostication study to show the value of automated pupillometry using a blinded approach to minimize self-fulfilling prophecy. Ann Neurol 2017;81:804-810. © 2017 American Neurological Association.

  6. Early 'visual' cortex activation correlates with superior verbal memory performance in the blind.

    PubMed

    Amedi, Amir; Raz, Noa; Pianka, Pazit; Malach, Rafael; Zohary, Ehud

    2003-07-01

    The visual cortex may be more modifiable than previously considered. Using functional magnetic resonance imaging (fMRI) in ten congenitally blind human participants, we found robust occipital activation during a verbal-memory task (in the absence of any sensory input), as well as during verb generation and Braille reading. We also found evidence for reorganization and specialization of the occipital cortex, along the anterior-posterior axis. Whereas anterior regions showed preference for Braille, posterior regions (including V1) showed preference for verbal-memory and verb generation (which both require memory of verbal material). No such occipital activation was found in sighted subjects. This difference between the groups was mirrored by superior performance of the blind in various verbal-memory tasks. Moreover, the magnitude of V1 activation during the verbal-memory condition was highly correlated with the blind individual's abilities in a variety of verbal-memory tests, suggesting that the additional occipital activation may have a functional role.

  7. Doxycycline in early CJD: a double-blinded randomised phase II and observational study.

    PubMed

    Varges, Daniela; Manthey, Henrike; Heinemann, Uta; Ponto, Claudia; Schmitz, Matthias; Schulz-Schaeffer, Walter J; Krasnianski, Anna; Breithaupt, Maren; Fincke, Fabian; Kramer, Katharina; Friede, Tim; Zerr, Inga

    2017-02-01

    The main objective of the present study is to study the therapeutic efficiency of doxycycline in a double-blinded randomised phase II study in a cohort of patients with sporadic Creutzfeldt-Jakob disease (sCJD). From the National Reference Center of TSE Surveillance in Germany, patients with probable or definite sCJD were recruited for a double-blinded randomised study with oral doxycycline (EudraCT 2006-003934-14). In addition, we analysed the data from patients with CJD who received compassionate treatment with doxycycline in a separate group. Potential factors which influence survival such as age at onset, gender, codon 129 polymorphism and cognitive functions were evaluated. The primary outcome measure was survival. Group 1: in the double-blinded randomised phase II study, 7 patients in the treatment group were compared with 5 controls. Group 2: 55 patients with sCJD treated with oral doxycycline were analysed and compared with 33 controls by a stratified propensity score applied to a Cox proportional hazard analysis. The results of both studies were combined by means of a random-effects meta-analysis. A slight increase in survival time in the doxycycline treatment group was observed (p=0.049, HR=0.63 (95% CI 0.402 to 0.999)). On the basis of our studies, a larger trial of doxycycline should be performed in persons in the earliest stages of CJD. EudraCT 2006-003934-14; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  8. Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) study.

    PubMed

    Findling, Robert L; Johnson, Jacqueline L; McClellan, Jon; Frazier, Jean A; Vitiello, Benedetto; Hamer, Robert M; Lieberman, Jeffrey A; Ritz, Louise; McNamara, Nora K; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

    2010-06-01

    To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed according to defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks. Of the 116 youths randomized in the acute trial, 54 entered maintenance treatment (molindone, n = 20; olanzapine, n = 13; risperidone, n = 21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (n = 15), inadequate efficacy (n = 14), or study nonadherence (n = 8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. Only 12% of youths with early-onset schizophrenia spectrum disorders continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for early-onset schizophrenia spectrum disorders. Clinical trial registry information-Treatment of Schizophrenia and Related Disorders in Children and Adolescents; URL: http://www.clinicaltrials.gov, unique identifier: NCT00053703. 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum Study (TEOSS)

    PubMed Central

    Findling, Robert L; Johnson, Jacqueline L; McClellan, Jon; Frazier, Jean A; Vitiello, Benedetto; Hamer, Robert M; Lieberman, Jeffrey A; Ritz, Louise; McNamara, Nora K; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

    2010-01-01

    OBJECTIVE To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders (EOSS). METHOD Patients (age 8–19 years) who had improved during an 8-week, randomized double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed following defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks. RESULTS Of the 116 youth randomized in the acute trial, 54 entered maintenance treatment (molindone, N=20; olanzapine, N=13; risperidone, N=21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (N=15), inadequate efficacy (N=14), or study non-adherence (N=8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom reduction or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. CONCLUSIONS Only 12 % of youth with EOSS continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for EOSS. PMID:20494268

  10. Differences in Early Stages of Tactile ERP Temporal Sequence (P100) in Cortical Organization during Passive Tactile Stimulation in Children with Blindness and Controls.

    PubMed

    Ortiz Alonso, Tomás; Santos, Juan Matías; Ortiz Terán, Laura; Borrego Hernández, Mayelin; Poch Broto, Joaquín; de Erausquin, Gabriel Alejandro

    2015-01-01

    Compared to their seeing counterparts, people with blindness have a greater tactile capacity. Differences in the physiology of object recognition between people with blindness and seeing people have been well documented, but not when tactile stimuli require semantic processing. We used a passive vibrotactile device to focus on the differences in spatial brain processing evaluated with event related potentials (ERP) in children with blindness (n = 12) vs. normally seeing children (n = 12), when learning a simple spatial task (lines with different orientations) or a task involving recognition of letters, to describe the early stages of its temporal sequence (from 80 to 220 msec) and to search for evidence of multi-modal cortical organization. We analysed the P100 of the ERP. Children with blindness showed earlier latencies for cognitive (perceptual) event related potentials, shorter reaction times, and (paradoxically) worse ability to identify the spatial direction of the stimulus. On the other hand, they are equally proficient in recognizing stimuli with semantic content (letters). The last observation is consistent with the role of P100 on somatosensory-based recognition of complex forms. The cortical differences between seeing control and blind groups, during spatial tactile discrimination, are associated with activation in visual pathway (occipital) and task-related association (temporal and frontal) areas. The present results show that early processing of tactile stimulation conveying cross modal information differs in children with blindness or with normal vision.

  11. Differences in Early Stages of Tactile ERP Temporal Sequence (P100) in Cortical Organization during Passive Tactile Stimulation in Children with Blindness and Controls

    PubMed Central

    Ortiz Alonso, Tomás; Santos, Juan Matías; Ortiz Terán, Laura; Borrego Hernández, Mayelin; Poch Broto, Joaquín; de Erausquin, Gabriel Alejandro

    2015-01-01

    Compared to their seeing counterparts, people with blindness have a greater tactile capacity. Differences in the physiology of object recognition between people with blindness and seeing people have been well documented, but not when tactile stimuli require semantic processing. We used a passive vibrotactile device to focus on the differences in spatial brain processing evaluated with event related potentials (ERP) in children with blindness (n = 12) vs. normally seeing children (n = 12), when learning a simple spatial task (lines with different orientations) or a task involving recognition of letters, to describe the early stages of its temporal sequence (from 80 to 220 msec) and to search for evidence of multi-modal cortical organization. We analysed the P100 of the ERP. Children with blindness showed earlier latencies for cognitive (perceptual) event related potentials, shorter reaction times, and (paradoxically) worse ability to identify the spatial direction of the stimulus. On the other hand, they are equally proficient in recognizing stimuli with semantic content (letters). The last observation is consistent with the role of P100 on somatosensory-based recognition of complex forms. The cortical differences between seeing control and blind groups, during spatial tactile discrimination, are associated with activation in visual pathway (occipital) and task-related association (temporal and frontal) areas. The present results show that early processing of tactile stimulation conveying cross modal information differs in children with blindness or with normal vision. PMID:26225827

  12. Secondary Prevention of Chronic PTSD by Early and Short-Term Administration of Escitalopram: A Prospective Randomized, Placebo-Controlled, Double-Blind Trial.

    PubMed

    Zohar, Joseph; Fostick, Leah; Juven-Wetzler, Alzabeta; Kaplan, Zeev; Shalev, Hadar; Schreiber, Gavriel; Miroshnik, Natalie; Shalev, Arieh Y; Stein, Dan J; Seedat, Soraya; Suliman, Sharain; Klein, Ehud

    Prospective studies have not identified a viable pharmacologic strategy for secondary prevention of posttraumatic stress disorder (PTSD). The authors examined whether preventive intervention via early and short-term administration of a selective serotonin reuptake inhibitor (SSRI), within 1 month of exposure to a traumatic event (before diagnosis of PTSD could be made), may reduce the severity of PTSD symptoms according to DSM-IV at 13 months' follow-up. Over 25,000 screening calls to patients referred to an emergency department for a traumatic event performed between June 2006 and December 2008 yielded 353 participants who were recruited within the month following a traumatic event . Participants were randomly assigned in a double-blind design to escitalopram (n = 176) or placebo (n = 177). The per-protocol analysis comprised 198 participants (escitalopram, n = 102; placebo, n = 96) who received treatment for 12 to 24 weeks and were available for follow-up at week 56. The primary outcome measure, the Clinician Administered PTSD Scale (CAPS), revealed no prevention effect. However, a secondary outcome, the Pittsburgh Sleep Quality Inventory (PSQI), showed better results for the SSRI group than for the placebo group. For a subset of participants who experienced intentional trauma (missile attacks, rape, or physical assault; n = 50), the prevention effect was found on both primary and secondary measures (CAPS, PSQI and measures of depression and global illness severity). Early and short-term administration of escitalopram was not shown to prevent PTSD, although it did improve sleep quality. In a subgroup of participants who experienced intentional trauma, however, this early-treatment approach may be effective as secondary prevention. This large study is the first to investigate the preventive effect of early administration of escitalopram on PTSD. It highlights the relevance of the type of trauma (intentional vs unintentional) to the outcome. Clinical

  13. Emotion-induced blindness reflects competition at early and late processing stages: an ERP study.

    PubMed

    Kennedy, Briana L; Rawding, Jennifer; Most, Steven B; Hoffman, James E

    2014-12-01

    Emotion-induced blindness (EIB) refers to impaired awareness of items appearing soon after an irrelevant, emotionally arousing stimulus. Superficially, EIB appears to be similar to the attentional blink (AB), a failure to report a target that closely follows another relevant target. Previous studies of AB using event-related potentials suggest that the AB results from interference with selection (N2 component) and consolidation (P3b component) of the second target into working memory. The present study applied a similar analysis to EIB and, similarly, found that an irrelevant emotional distractor suppressed the N2 and P3b components associated with the following target at short lags. Emotional distractors also elicited a positive deflection that appeared to be similar to the PD component, which has been associated with attempts to suppress salient, irrelevant distractors (Kiss, Grubert, Petersen, & Eimer, 2012; Sawaki, Geng, & Luck, 2012; Sawaki & Luck, 2010). These results suggest that irrelevant emotional pictures gain access to working memory, even when observers are attempting to ignore them and, like the AB, prevent access of a closely following target.

  14. Blindness - resources

    MedlinePlus

    Resources - blindness ... The following organizations are good resources for information on blindness : American Foundation for the Blind -- www.afb.org Foundation Fighting Blindness -- www.blindness.org National Eye Institute -- ...

  15. Increased regional cerebral blood flow but normal distribution of GABAA receptor in the visual cortex of subjects with early-onset blindness.

    PubMed

    Mishina, Masahiro; Senda, Michio; Kiyosawa, Motohiro; Ishiwata, Kiichi; De Volder, Anne G; Nakano, Hideki; Toyama, Hinako; Oda, Kei-ichi; Kimura, Yuichi; Ishii, Kenji; Sasaki, Touru; Ohyama, Masashi; Komaba, Yuichi; Kobayashi, Shirou; Kitamura, Shin; Katayama, Yasuo

    2003-05-01

    Before the completion of visual development, visual deprivation impairs synaptic elimination in the visual cortex. The purpose of this study was to determine whether the distribution of central benzodiazepine receptor (BZR) is also altered in the visual cortex in subjects with early-onset blindness. Positron emission tomography was carried out with [(15)O]water and [(11)C]flumazenil on six blind subjects and seven sighted controls at rest. We found that the CBF was significantly higher in the visual cortex for the early-onset blind subjects than for the sighted control subjects. However, there was no significant difference in the BZR distribution in the visual cortex for the subject with early-onset blindness than for the sighted control subjects. These results demonstrated that early visual deprivation does not affect the distribution of GABA(A) receptors in the visual cortex with the sensitivity of our measurements. Synaptic elimination may be independent of visual experience in the GABAergic system of the human visual cortex during visual development.

  16. Cortical GABAergic Interneurons in Cross-Modal Plasticity following Early Blindness

    PubMed Central

    Desgent, Sébastien; Ptito, Maurice

    2012-01-01

    Early loss of a given sensory input in mammals causes anatomical and functional modifications in the brain via a process called cross-modal plasticity. In the past four decades, several animal models have illuminated our understanding of the biological substrates involved in cross-modal plasticity. Progressively, studies are now starting to emphasise on cell-specific mechanisms that may be responsible for this intermodal sensory plasticity. Inhibitory interneurons expressing γ-aminobutyric acid (GABA) play an important role in maintaining the appropriate dynamic range of cortical excitation, in critical periods of developmental plasticity, in receptive field refinement, and in treatment of sensory information reaching the cerebral cortex. The diverse interneuron population is very sensitive to sensory experience during development. GABAergic neurons are therefore well suited to act as a gate for mediating cross-modal plasticity. This paper attempts to highlight the links between early sensory deprivation, cortical GABAergic interneuron alterations, and cross-modal plasticity, discuss its implications, and further provide insights for future research in the field. PMID:22720175

  17. SA19. N-Acetyl-Cysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis

    PubMed Central

    Do, Kim; Seidman, Larry J.; Fournier, Margot; Xin, Lijing; Cleusix, Martine; Baumann, Philipp S.; Ferrari, Carina; Cousins, Ann; Alameda, Luis; Gholam-Rezaee, Mehdi; Golay, Philippe; Jenni, Raoul; Woo, T-U Wilson; Keshavan, Matcheri S.; Eap, Chin B.; Wojcik, Joanne; Cuenod, Michel; Buclin, Thierry; Gruetter, Rolf; Conus, Philippe

    2017-01-01

    Abstract Background: Biomarker-guided treatments are needed in psychiatry and previous data suggest redox dysregulation / oxidative stress may be a target in schizophrenia (1,2). A previous add-on trial with the antioxidant N-Acetyl-Cysteine (NAC) led to negative symptoms reductions in chronic patients (3). We aim to study NAC impact on symptoms and neurocognition in early psychosis (EP) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment. Methods: In a double-blind, randomized, placebo-controlled trial in 63 EP patients, we assessed the effect of NAC supplementation (2700 mg/day, 6 months) on PANSS, neurocognition (MATRICS Consensus Cognitive Battery [MCCB]), and redox markers (brain GSH [GSH-mPFC], blood cells GSH [GSH-BC] levels, and GSH peroxidase activity [GPx-BC]). Results: No changes in negative, positive symptoms, or functional outcome were observed with NAC, but significant improvements were found in favor of NAC on the MCCB Processing Speed factor and two of its components: Trail Making and Verbal Fluency. NAC leads to increases in GSH-mPFC by 23% (P = .005) and GSH-BC by 19% (P = .05). In patients with high-baseline GPx-BC (>22.3U/gHb), subgroup explorations revealed an improvement with NAC of positive symptoms when compared to patients with low-baseline GPx (P = .02), with an improvement of positive symptoms in parallel with that of the redox status. Conclusion: In conclusion, NAC supplementation in a limited sample of EP patients did not improve negative symptoms, which were at modest levels at baseline. However, NAC leads to neurocognition improvement as well as to brain GSH levels increases, pointing to good target engagement. Blood GPx activity, a redox peripheral index associated with brain GSH levels, could help to identify a subgroup of patients who improve their positive symptoms with NAC. Future trials with antioxidant in EP should consider biomarker-guided treatment. References 1

  18. Seismic imaging of the Main Frontal Thrust in Nepal reveals a shallow décollement and blind thrusting

    NASA Astrophysics Data System (ADS)

    Almeida, Rafael V.; Hubbard, Judith; Liberty, Lee; Foster, Anna; Sapkota, Soma Nath

    2018-07-01

    Because great earthquakes in the Himalaya have an average recurrence interval exceeding 500 yr, most of what we know about past earthquakes comes from paleoseismology and tectonic geomorphology studies of the youngest fault system there, the Main Frontal Thrust (MFT). However, these data are sparse relative to fault segmentation and length, and interpretations are often hard to validate in the absence of information about fault geometry. Here, we image the upper two km of strata in the vicinity of the fault tip of the MFT in central Nepal (around the town of Bardibas) applying a pre-stack migration approach to two new seismic reflection profiles that we interpret using quantitative fault-bend folding theory. Our results provide direct evidence that a shallow décollement produces both emergent (Patu thrust) and blind (Bardibas thrust) fault strands. We show that the décollement lies about 2 km below the land surface near the fault tip, and steps down to a regional 5 km deep décollement level to the north. This implies that there is significant variation in the depth of the décollement. We demonstrate that some active faults do not reach the surface, and therefore paleoseismic trenching alone cannot characterize the earthquake history at these locations. Although blind, these faults have associated growth strata that allow us to infer their most recent displacement history. We present the first direct evidence of fault dip on two fault strands of the MFT at depth that can allow terrace uplift measurements to be more accurately converted to fault slip. We identify a beveled erosional surface buried beneath Quaternary sediments, indicating that strath surface formation is modulated by both climate-related base level changes and tectonics. Together, these results indicate that subsurface imaging, in conjunction with traditional paleoseismological tools, can best characterize the history of fault slip in the Himalaya and other similar thrust fault systems.

  19. Novel loss-of-function variants in DIAPH1 associated with syndromic microcephaly, blindness, and early onset seizures.

    PubMed

    Al-Maawali, Almundher; Barry, Brenda J; Rajab, Anna; El-Quessny, Malak; Seman, Ann; Coury, Stephanie Newton; Barkovich, A James; Yang, Edward; Walsh, Christopher A; Mochida, Ganeshwaran H; Stoler, Joan M

    2016-02-01

    Exome sequencing identified homozygous loss-of-function variants in DIAPH1 (c.2769delT; p.F923fs and c.3145C>T; p.R1049X) in four affected individuals from two unrelated consanguineous families. The affected individuals in our report were diagnosed with postnatal microcephaly, early-onset epilepsy, severe vision impairment, and pulmonary symptoms including bronchiectasis and recurrent respiratory infections. A heterozygous DIAPH1 mutation was originally reported in one family with autosomal dominant deafness. Recently, however, a homozygous nonsense DIAPH1 mutation (c.2332C4T; p.Q778X) was reported in five siblings in a single family affected by microcephaly, blindness, early onset seizures, developmental delay, and bronchiectasis. The role of DIAPH1 was supported using parametric linkage analysis, RNA and protein studies in their patients' cell lines and further studies in human neural progenitors cells and a diap1 knockout mouse. In this report, the proband was initially brought to medical attention for profound metopic synostosis. Additional concerns arose when his head circumference did not increase after surgical release at 5 months of age and he was diagnosed with microcephaly and epilepsy at 6 months of age. Clinical exome analysis identified a homozygous DIAPH1 mutation. Another homozygous DIAPH1 mutation was identified in the research exome analysis of a second family with three siblings presenting with a similar phenotype. Importantly, no hearing impairment is reported in the homozygous affected individuals or in the heterozygous carrier parents in any of the families demonstrating the autosomal recessive microcephaly phenotype. These additional families provide further evidence of the likely causal relationship between DIAPH1 mutations and a neurodevelopmental disorder. © 2016 Wiley Periodicals, Inc.

  20. Comparison of successive transition states for folding reveals alternative early folding pathways of two homologous proteins

    PubMed Central

    Calosci, Nicoletta; Chi, Celestine N.; Richter, Barbara; Camilloni, Carlo; Engström, Åke; Eklund, Lars; Travaglini-Allocatelli, Carlo; Gianni, Stefano; Vendruscolo, Michele; Jemth, Per

    2008-01-01

    The energy landscape theory provides a general framework for describing protein folding reactions. Because a large number of studies, however, have focused on two-state proteins with single well-defined folding pathways and without detectable intermediates, the extent to which free energy landscapes are shaped up by the native topology at the early stages of the folding process has not been fully characterized experimentally. To this end, we have investigated the folding mechanisms of two homologous three-state proteins, PTP-BL PDZ2 and PSD-95 PDZ3, and compared the early and late transition states on their folding pathways. Through a combination of Φ value analysis and molecular dynamics simulations we obtained atomic-level structures of the transition states of these homologous three-state proteins and found that the late transition states are much more structurally similar than the early ones. Our findings thus reveal that, while the native state topology defines essentially in a unique way the late stages of folding, it leaves significant freedom to the early events, a result that reflects the funneling of the free energy landscape toward the native state. PMID:19033470

  1. Quantitative Tissue Proteomics Analysis Reveals Versican as Potential Biomarker for Early-Stage Hepatocellular Carcinoma.

    PubMed

    Naboulsi, Wael; Megger, Dominik A; Bracht, Thilo; Kohl, Michael; Turewicz, Michael; Eisenacher, Martin; Voss, Don Marvin; Schlaak, Jörg F; Hoffmann, Andreas-Claudius; Weber, Frank; Baba, Hideo A; Meyer, Helmut E; Sitek, Barbara

    2016-01-04

    Hepatocellular carcinoma (HCC) is one of the most aggressive tumors, and the treatment outcome of this disease is improved when the cancer is diagnosed at an early stage. This requires biomarkers allowing an accurate and early tumor diagnosis. To identify potential markers for such applications, we analyzed a patient cohort consisting of 50 patients (50 HCC and 50 adjacent nontumorous tissue samples as controls) using two independent proteomics approaches. We performed label-free discovery analysis on 19 HCC and corresponding tissue samples. The data were analyzed considering events known to take place in early events of HCC development, such as abnormal regulation of Wnt/b-catenin and activation of receptor tyrosine kinases (RTKs). 31 proteins were selected for verification experiments. For this analysis, the second set of the patient cohort (31 HCC and corresponding tissue samples) was analyzed using selected (multiple) reaction monitoring (SRM/MRM). We present the overexpression of ATP-dependent RNA helicase (DDX39), Fibulin-5 (FBLN5), myristoylated alanine-rich C-kinase substrate (MARCKS), and Serpin H1 (SERPINH1) in HCC for the first time. We demonstrate Versican core protein (VCAN) to be significantly associated with well differentiated and low-stage HCC. We revealed for the first time the evidence of VCAN as a potential biomarker for early-HCC diagnosis.

  2. Early botulinum toxin treatment for spastic pes equinovarus--a randomized double-blind placebo-controlled study.

    PubMed

    Fietzek, U M; Kossmehl, P; Schelosky, L; Ebersbach, G; Wissel, J

    2014-08-01

    Spastic pes equinovarus is a frequent pathological posture of the lower extremity. Botulinum toxin (BoNT/A) has been successfully applied to treat lower limb spasticity. However, the best time to initiate treatment remains unclear. A beneficial effect of an early treatment has been suggested in previous studies. A single-centre double-blind randomized placebo-controlled trial was performed to investigate the efficacy of BoNT/A to reduce muscle hypertonicity at the ankle. Fifty-two patients with unilateral or bilateral spastic pes equinovarus with a modified Ashworth score (mAS) of at least 1+ after stroke, traumatic brain injury or hypoxic encephalopathy were allocated to receive either BoNT/A or placebo treatment. A second, open injection was optional at week 12. Patients received unilateral or bilateral injections with 230 or 460 U onabotulinumtoxinA, respectively. The course of the mAS was explored during the open study phase. Patients who had received BoNT/A treatment had lower mAS compared with placebo at week 12 (P < 0.01). During the open label phase, patients from the placebo group showed further deterioration of muscle tone despite starting from a similar baseline and receiving BoNT treatment. Spastic feet that had received BoNT/A in the first cycle had comparatively lower mAS scores over all follow-up data and at week 24 (P < 0.01). The study demonstrates a reduction of muscular hypertonicity in spastic pes equines with BoNT/A treatment given during the first 3 months after the lesion. Exploratory analyses of the course of muscular hypertonicity during the open phase favour earlier to later treatment. © 2014 The Author(s) European Journal of Neurology © 2014 EAN.

  3. Effect of reading on blood flow changes in the posterior cerebral artery in early blind and sighted people--A transcranial Doppler study.

    PubMed

    Viski, Sandor; Orgovan, David; Szabo, Katalin; Rosengarten, Bernhard; Csiba, Laszlo; Olah, Laszlo

    2016-04-15

    Neuroimaging studies proved that Braille reading resulted in visual cortex activation in blind people, however, very few data are available about the measure of flow increase in these subjects. Therefore, we investigated the flow response in the posterior cerebral artery (PCA) of eleven early blind and ten sighted subjects induced by reading Braille and print, respectively. Two experimental protocols were used in both groups: PCA flow velocity during reading was compared to the resting phase and "NLC" phase (volunteers "read" non-lexical characters; e.g. .,-.:,-.:...,). The use of these experimental protocols allowed to investigate separately the effect of "light stimulus+print reading" versus "print reading alone" in sighted, and "hand/finger movement+Braille reading" versus "Braille reading alone" in blind subjects. The flow response in the PCA evoked by "Braille reading alone" in blind (10.5±4.5%) and "print reading alone" in sighted subjects (8.1±3.5%) was similar. The flow increase induced by "hand/finger movement+Braille reading" and by "Braille reading alone" did not differ in blind people, however, "light stimulus+print reading" in sighted subjects caused higher PCA flow increase (25.9±6.9%) than "print reading alone" (8.1±3.5%). The similar PCA flow response induced by Braille and print reading alone suggested a similar degree of occipital cortex activation in blind and sighted subjects. In sighted people, the 3-times higher flow velocity increase induced by "light stimulus+print reading" compared with "print reading alone" indicated that 2/3 of PCA flow increase during reading was due to the light stimulus and only 1/3 of flow response was caused by reading alone. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Hepatitis C Virus Reveals a Novel Early Control in Acute Immune Response

    PubMed Central

    Arnaud, Noëlla; Dabo, Stéphanie; Akazawa, Daisuke; Fukasawa, Masayoshi; Shinkai-Ouchi, Fumiko; Hugon, Jacques; Wakita, Takaji; Meurs, Eliane F.

    2011-01-01

    Recognition of viral RNA structures by the intracytosolic RNA helicase RIG-I triggers induction of innate immunity. Efficient induction requires RIG-I ubiquitination by the E3 ligase TRIM25, its interaction with the mitochondria-bound MAVS protein, recruitment of TRAF3, IRF3- and NF-κB-kinases and transcription of Interferon (IFN). In addition, IRF3 alone induces some of the Interferon-Stimulated Genes (ISGs), referred to as early ISGs. Infection of hepatocytes with Hepatitis C virus (HCV) results in poor production of IFN despite recognition of the viral RNA by RIG-I but can lead to induction of early ISGs. HCV was shown to inhibit IFN production by cleaving MAVS through its NS3/4A protease and by controlling cellular translation through activation of PKR, an eIF2α-kinase containing dsRNA-binding domains (DRBD). Here, we have identified a third mode of control of IFN induction by HCV. Using HCVcc and the Huh7.25.CD81 cells, we found that HCV controls RIG-I ubiquitination through the di-ubiquitine-like protein ISG15, one of the early ISGs. A transcriptome analysis performed on Huh7.25.CD81 cells silenced or not for PKR and infected with JFH1 revealed that HCV infection leads to induction of 49 PKR-dependent genes, including ISG15 and several early ISGs. Silencing experiments revealed that this novel PKR-dependent pathway involves MAVS, TRAF3 and IRF3 but not RIG-I, and that it does not induce IFN. Use of PKR inhibitors showed that this pathway requires the DRBD but not the kinase activity of PKR. We then demonstrated that PKR interacts with HCV RNA and MAVS prior to RIG-I. In conclusion, HCV recruits PKR early in infection as a sensor to trigger induction of several IRF3-dependent genes. Among those, ISG15 acts to negatively control the RIG-I/MAVS pathway, at the level of RIG-I ubiquitination.These data give novel insights in the machinery involved in the early events of innate immune response. PMID:22022264

  5. N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis

    PubMed Central

    Conus, Philippe; Seidman, Larry J; Fournier, Margot; Xin, Lijing; Cleusix, Martine; Baumann, Philipp S; Ferrari, Carina; Cousins, Ann; Alameda, Luis; Gholam-Rezaee, Mehdi; Golay, Philippe; Jenni, Raoul; Woo, T -U Wilson; Keshavan, Matcheri S; Eap, Chin B; Wojcik, Joanne; Cuenod, Michel; Buclin, Thierry; Gruetter, Rolf

    2018-01-01

    Abstract Biomarker-guided treatments are needed in psychiatry, and previous data suggest oxidative stress may be a target in schizophrenia. A previous add-on trial with the antioxidant N-acetylcysteine (NAC) led to negative symptom reductions in chronic patients. We aim to study NAC’s impact on symptoms and neurocognition in early psychosis (EP) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment. In a double-blind, randomized, placebo-controlled trial in 63 EP patients, we assessed the effect of NAC supplementation (2700 mg/day, 6 months) on PANSS, neurocognition, and redox markers (brain GSH [GSHmPFC], blood cells GSH levels [GSHBC], GSH peroxidase activity [GPxBC]). No changes in negative or positive symptoms or functional outcome were observed with NAC, but significant improvements were found in favor of NAC on neurocognition (processing speed). NAC also led to increases of GSHmPFC by 23% (P = .005) and GSHBC by 19% (P = .05). In patients with high-baseline GPxBC compared to low-baseline GPxBC, subgroup explorations revealed a link between changes of positive symptoms and changes of redox status with NAC. In conclusion, NAC supplementation in a limited sample of EP patients did not improve negative symptoms, which were at modest baseline levels. However, NAC led to some neurocognitive improvements and an increase in brain GSH levels, indicating good target engagement. Blood GPx activity, a redox peripheral index associated with brain GSH levels, could help identify a subgroup of patients who improve their positive symptoms with NAC. Thus, future trials with antioxidants in EP should consider biomarker-guided treatment. PMID:29462456

  6. Bayesian Morphological Clock Methods Resurrect Placoderm Monophyly and Reveal Rapid Early Evolution in Jawed Vertebrates.

    PubMed

    King, Benedict; Qiao, Tuo; Lee, Michael S Y; Zhu, Min; Long, John A

    2017-07-01

    The phylogeny of early gnathostomes provides an important framework for understanding one of the most significant evolutionary events, the origin and diversification of jawed vertebrates. A series of recent cladistic analyses have suggested that the placoderms, an extinct group of armoured fish, form a paraphyletic group basal to all other jawed vertebrates. We revised and expanded this morphological data set, most notably by sampling autapomorphies in a similar way to parsimony-informative traits, thus ensuring this data (unlike most existing morphological data sets) satisfied an important assumption of Bayesian tip-dated morphological clock approaches. We also found problems with characters supporting placoderm paraphyly, including character correlation and incorrect codings. Analysis of this data set reveals that paraphyly and monophyly of core placoderms (excluding maxillate forms) are essentially equally parsimonious. The two alternative topologies have different root positions for the jawed vertebrates but are otherwise similar. However, analysis using tip-dated clock methods reveals strong support for placoderm monophyly, due to this analysis favoring trees with more balanced rates of evolution. Furthermore, enforcing placoderm paraphyly results in higher levels and unusual patterns of rate heterogeneity among branches, similar to that generated from simulated trees reconstructed with incorrect root positions. These simulations also show that Bayesian tip-dated clock methods outperform parsimony when the outgroup is largely uninformative (e.g., due to inapplicable characters), as might be the case here. The analysis also reveals that gnathostomes underwent a rapid burst of evolution during the Silurian period which declined during the Early Devonian. This rapid evolution during a period with few articulated fossils might partly explain the difficulty in ascertaining the root position of jawed vertebrates. © The Author(s) 2016. Published by Oxford University

  7. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial

    PubMed Central

    Raman, Subha V; Hor, Kan N; Mazur, Wojciech; Halnon, Nancy J; Kissel, John T; He, Xin; Tran, Tam; Smart, Suzanne; McCarthy, Beth; Taylor, Michael D; Jefferies, John L; Rafael-Fortney, Jill A; Lowe, Jeovanna; Roble, Sharon L; Cripe, Linda H

    2015-01-01

    Summary Background Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy and myocardial damage precedes decline in left ventricular systolic function. We tested the efficacy of eplerenone on top of background therapy in patients with Duchenne muscular dystrophy with early myocardial disease. Methods In this randomised, double-blind, placebo-controlled trial, boys from three centres in the USA aged 7 years or older with Duchenne muscular dystrophy, myocardial damage by late gadolinium enhancement cardiac MRI and preserved ejection fraction received either eplerenone 25 mg or placebo orally, every other day for the first month and once daily thereafter, in addition to background clinician-directed therapy with either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Computer-generated randomisation was done centrally using block sizes of four and six, and only the study statistician and the investigational pharmacy had the preset randomisation assignments. The primary outcome was change in left ventricular circumferential strain (Ecc) at 12 months, a measure of contractile dysfunction. Safety was established through serial serum potassium levels and measurement of cystatin C, a non-creatinine measure of kidney function. This trial is registered with ClinicalTrials.gov, number NCT01521546. Findings Between Jan 26, 2012, and July 3, 2013, 188 boys were screened and 42 were enrolled. 20 were randomly assigned to receive eplerenone and 22 to receive placebo, of whom 20 in the eplerenone group and 20 in the placebo group completed baseline, 6-month, and 12-month visits. After 12 months, decline in left ventricular circumferential strain was less in those who received eplerenone than in those who received placebo (median ΔEcc 1.0 [IQR 0.3–2.2]vs2.2 [1.3–3.1]; p=0.020). Cystatin C concentrations remained normal in both groups, and all non-haemolysed blood samples showed normal potassium

  8. An Integrated Phosphoproteomics Work Flow Reveals Extensive Network Regulation in Early Lysophosphatidic Acid Signaling*

    PubMed Central

    Schreiber, Thiemo B.; Mäusbacher, Nina; Kéri, György; Cox, Jürgen; Daub, Henrik

    2010-01-01

    Lysophosphatidic acid (LPA) induces a variety of cellular signaling pathways through the activation of its cognate G protein-coupled receptors. To investigate early LPA responses and assess the contribution of epidermal growth factor (EGF) receptor transactivation in LPA signaling, we performed phosphoproteomics analyses of both total cell lysate and protein kinase-enriched fractions as complementary strategies to monitor phosphorylation changes in A498 kidney carcinoma cells. Our integrated work flow enabled the identification and quantification of more than 5,300 phosphorylation sites of which 224 were consistently regulated by LPA. In addition to induced phosphorylation events, we also obtained evidence for early dephosphorylation reactions due to rapid phosphatase regulation upon LPA treatment. Phosphorylation changes induced by direct heparin-binding EGF-like growth factor-mediated EGF receptor activation were typically weaker and only detected on a subset of LPA-regulated sites, indicating signal integration among EGF receptor transactivation and other LPA-triggered pathways. Our results reveal rapid phosphoregulation of many proteins not yet implicated in G protein-coupled receptor signaling and point to various additional mechanisms by which LPA might regulate cell survival and migration as well as gene transcription on the molecular level. Moreover, our phosphoproteomics analysis of both total lysate and kinase-enriched fractions provided highly complementary parts of the LPA-regulated signaling network and thus represents a useful and generic strategy toward comprehensive signaling studies on a system-wide level. PMID:20071362

  9. Single-Cell RNA-Seq Reveals Dynamic Early Embryonic-like Programs during Chemical Reprogramming.

    PubMed

    Zhao, Ting; Fu, Yao; Zhu, Jialiang; Liu, Yifang; Zhang, Qian; Yi, Zexuan; Chen, Shi; Jiao, Zhonggang; Xu, Xiaochan; Xu, Junquan; Duo, Shuguang; Bai, Yun; Tang, Chao; Li, Cheng; Deng, Hongkui

    2018-06-12

    Chemical reprogramming provides a powerful platform for exploring the molecular dynamics that lead to pluripotency. Although previous studies have uncovered an intermediate extraembryonic endoderm (XEN)-like state during this process, the molecular underpinnings of pluripotency acquisition remain largely undefined. Here, we profile 36,199 single-cell transcriptomes at multiple time points throughout a highly efficient chemical reprogramming system using RNA-sequencing and reconstruct their progression trajectories. Through identifying sequential molecular events, we reveal that the dynamic early embryonic-like programs are key aspects of successful reprogramming from XEN-like state to pluripotency, including the concomitant transcriptomic signatures of two-cell (2C) embryonic-like and early pluripotency programs and the epigenetic signature of notable genome-wide DNA demethylation. Moreover, via enhancing the 2C-like program by fine-tuning chemical treatment, the reprogramming process is remarkably accelerated. Collectively, our findings offer a high-resolution dissection of cell fate dynamics during chemical reprogramming and shed light on mechanistic insights into the nature of induced pluripotency. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. EEG reveals an early influence of social conformity on visual processing in group pressure situations.

    PubMed

    Trautmann-Lengsfeld, Sina Alexa; Herrmann, Christoph Siegfried

    2013-01-01

    Humans are social beings and often have to perceive and perform within groups. In conflict situations, this puts them under pressure to either adhere to the group opinion or to risk controversy with the group. Psychological experiments have demonstrated that study participants adapt to erroneous group opinions in visual perception tasks, which they can easily solve correctly when performing on their own. Until this point, however, it is unclear whether this phenomenon of social conformity influences early stages of perception that might not even reach awareness or later stages of conscious decision-making. Using electroencephalography, this study has revealed that social conformity to the wrong group opinion resulted in a decrease of the posterior-lateral P1 in line with a decrease of the later centro-parietal P3. These results suggest that group pressure situations impact early unconscious visual perceptual processing, which results in a later diminished stimulus discrimination and an adaptation even to the wrong group opinion. These findings might have important implications for understanding social behavior in group settings and are discussed within the framework of social influence on eyewitness testimony.

  11. Dynamic landscape of pancreatic carcinogenesis reveals early molecular networks of malignancy.

    PubMed

    Kong, Bo; Bruns, Philipp; Behler, Nora A; Chang, Ligong; Schlitter, Anna Melissa; Cao, Jing; Gewies, Andreas; Ruland, Jürgen; Fritzsche, Sina; Valkovskaya, Nataliya; Jian, Ziying; Regel, Ivonne; Raulefs, Susanne; Irmler, Martin; Beckers, Johannes; Friess, Helmut; Erkan, Mert; Mueller, Nikola S; Roth, Susanne; Hackert, Thilo; Esposito, Irene; Theis, Fabian J; Kleeff, Jörg; Michalski, Christoph W

    2018-01-01

    The initial steps of pancreatic regeneration versus carcinogenesis are insufficiently understood. Although a combination of oncogenic Kras and inflammation has been shown to induce malignancy, molecular networks of early carcinogenesis remain poorly defined. We compared early events during inflammation, regeneration and carcinogenesis on histological and transcriptional levels with a high temporal resolution using a well-established mouse model of pancreatitis and of inflammation-accelerated Kras G12D -driven pancreatic ductal adenocarcinoma. Quantitative expression data were analysed and extensively modelled in silico. We defined three distinctive phases-termed inflammation, regeneration and refinement-following induction of moderate acute pancreatitis in wild-type mice. These corresponded to different waves of proliferation of mesenchymal, progenitor-like and acinar cells. Pancreas regeneration required a coordinated transition of proliferation between progenitor-like and acinar cells. In mice harbouring an oncogenic Kras mutation and challenged with pancreatitis, there was an extended inflammatory phase and a parallel, continuous proliferation of mesenchymal, progenitor-like and acinar cells. Analysis of high-resolution transcriptional data from wild-type animals revealed that organ regeneration relied on a complex interaction of a gene network that normally governs acinar cell homeostasis, exocrine specification and intercellular signalling. In mice with oncogenic Kras, a specific carcinogenic signature was found, which was preserved in full-blown mouse pancreas cancer. These data define a transcriptional signature of early pancreatic carcinogenesis and a molecular network driving formation of preneoplastic lesions, which allows for more targeted biomarker development in order to detect cancer earlier in patients with pancreatitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  12. Cortical network differences in the sighted versus early blind for recognition of human-produced action sounds

    PubMed Central

    Lewis, James W.; Frum, Chris; Brefczynski-Lewis, Julie A.; Talkington, William J.; Walker, Nathan A.; Rapuano, Kristina M.; Kovach, Amanda L.

    2012-01-01

    Both sighted and blind individuals can readily interpret meaning behind everyday real-world sounds. In sighted listeners, we previously reported that regions along the bilateral posterior superior temporal sulci (pSTS) and middle temporal gyri (pMTG) are preferentially activated when presented with recognizable action sounds. These regions have generally been hypothesized to represent primary loci for complex motion processing, including visual biological motion processing and audio-visual integration. However, it remained unclear whether, or to what degree, life-long visual experience might impact functions related to hearing perception or memory of sound-source actions. Using functional magnetic resonance imaging (fMRI), we compared brain regions activated in congenitally blind versus sighted listeners in response to hearing a wide range of recognizable human-produced action sounds (excluding vocalizations) versus unrecognized, backward-played versions of those sounds. Here we show that recognized human action sounds commonly evoked activity in both groups along most of the left pSTS/pMTG complex, though with relatively greater activity in the right pSTS/pMTG by the blind group. These results indicate that portions of the postero-lateral temporal cortices contain domain-specific hubs for biological and/or complex motion processing independent of sensory-modality experience. Contrasting the two groups, the sighted listeners preferentially activated bilateral parietal plus medial and lateral frontal networks, while the blind listeners preferentially activated left anterior insula plus bilateral anterior calcarine and medial occipital regions, including what would otherwise have been visual-related cortex. These global-level network differences suggest that blind and sighted listeners may preferentially use different memory retrieval strategies when attempting to recognize action sounds. PMID:21305666

  13. Geologically Controlled Isotope-Time Patterns Reveal Early Differentiation and Crust Formation Processes

    NASA Astrophysics Data System (ADS)

    Bennett, V. C.; Nutman, A. P.

    2014-12-01

    The mechanisms of continental crust production and evolution in the early Earth remain controversial, as are questions of the relative roles of early differentiation versus subsequent tectonic procssing in creating Earth's chemical signatures. Here we present geologic observations integrated with whole rock major, trace element and Sm-Nd isotopic signatures and combined with U-Pb and Lu-Hf isotopic compositions of zircon populations from the same rocks, from the most extensive early rock record comprising the 3.9 Ga to 3.6 Ga terranes of southwest Greenland. These data reveal repeated patterns of formation of juvenile TTG crust and associated mafic and ultramafic rocks in convergent margin settings followed by formation of more evolved granites [1]. Our new zircon Lu-Hf data from rare 3.6-3.7 Ga tonalites within the Itsaq Gneiss Complex, obtained from single component, non-migmatitic gneisses with simple zircon populations, limited within sample Hf isotopic variability and accurate U-Pb ages, now document extraction of juvenile tonalites from a near chondritic mantle source between 3.9 Ga and 3.6 Ga. The more evolved, granitic rocks in each area show slightly negative initial ɛHf in accord with crustal reworking of the older (3.8-3.9 Ga) gniesses. There is no evidence for Hadean material in the sources of the granitoids. The Hf isotope-time patterns are consistent with juvenile crust production from a mantle source that experienced only modest amounts of prior crustal extraction. They are distinct from those predicted by reprocessing of an enriched Hadean mafic crust, as has been proposed for this region [2] and for the source of the Hadean Jack Hills zircons [3]. The well-documented, time decreasing, positive 142Nd anomalies [e.g., 4] from these rocks are further evidence of crustal derivation from a convecting mantle source, rather than reworking of an enriched mafic lithosphere. The 143Nd isotopic -time patterns are more complex, reflecting the interplay

  14. Population genomic analysis of elongated skulls reveals extensive female-biased immigration in Early Medieval Bavaria

    PubMed Central

    Veeramah, Krishna R.; Rott, Andreas; Groß, Melanie; López, Saioa; Kirsanow, Karola; Sell, Christian; Blöcher, Jens; Link, Vivian; Hofmanová, Zuzana; Peters, Joris; Trautmann, Bernd; Gairhos, Anja; Haberstroh, Jochen; Päffgen, Bernd; Hellenthal, Garrett; Haas-Gebhard, Brigitte; Harbeck, Michaela; Burger, Joachim

    2018-01-01

    Modern European genetic structure demonstrates strong correlations with geography, while genetic analysis of prehistoric humans has indicated at least two major waves of immigration from outside the continent during periods of cultural change. However, population-level genome data that could shed light on the demographic processes occurring during the intervening periods have been absent. Therefore, we generated genomic data from 41 individuals dating mostly to the late 5th/early 6th century AD from present-day Bavaria in southern Germany, including 11 whole genomes (mean depth 5.56×). In addition we developed a capture array to sequence neutral regions spanning a total of 5 Mb and 486 functional polymorphic sites to high depth (mean 72×) in all individuals. Our data indicate that while men generally had ancestry that closely resembles modern northern and central Europeans, women exhibit a very high genetic heterogeneity; this includes signals of genetic ancestry ranging from western Europe to East Asia. Particularly striking are women with artificial skull deformations; the analysis of their collective genetic ancestry suggests an origin in southeastern Europe. In addition, functional variants indicate that they also differed in visible characteristics. This example of female-biased migration indicates that complex demographic processes during the Early Medieval period may have contributed in an unexpected way to shape the modern European genetic landscape. Examination of the panel of functional loci also revealed that many alleles associated with recent positive selection were already at modern-like frequencies in European populations ∼1,500 years ago. PMID:29531040

  15. Synchrotron radiation reveals the identity of the large felid from Monte Argentario (Early Pleistocene, Italy).

    PubMed

    Cherin, Marco; Iurino, Dawid A; Zanatta, Marco; Fernandez, Vincent; Paciaroni, Alessandro; Petrillo, Caterina; Rettori, Roberto; Sardella, Raffaele

    2018-05-29

    We describe here a partial skull with associated mandible of a large felid from Monte Argentario, Italy (Early Pleistocene; ~1.5 million years). Propagation x-ray phase-contrast synchrotron microtomography of the specimen, still partially embedded in the rock matrix, allows ascribing it reliably to Acinonyx pardinensis, one of the most intriguing extinct carnivorans of the Old World Plio-Pleistocene. The analysis of images and 3D models obtained through synchrotron microtomography - here applied for the first time on a Plio-Pleistocene carnivoran - reveals a mosaic of cheetah-like and Panthera-like features, with the latter justifying previous attributions of the fossil to the extinct Eurasian jaguar Panthera gombaszoegensis. Similarly, we reassign to A. pardinensis some other Italian materials previously referred to P. gombaszoegensis (sites of Pietrafitta and Ellera di Corciano). The recognition of Panthera-like characters in A. pardinensis leads to reconsidering the ecological role of this species, whose hunting strategy was likely to be different from those of the living cheetah. Furthermore, we hypothesise that the high intraspecific variation in body size in A. pardinensis can be the result of sexual dimorphism, as observed today in all large-sized felids.

  16. Early Development of Functional Network Segregation Revealed by Connectomic Analysis of the Preterm Human Brain.

    PubMed

    Cao, Miao; He, Yong; Dai, Zhengjia; Liao, Xuhong; Jeon, Tina; Ouyang, Minhui; Chalak, Lina; Bi, Yanchao; Rollins, Nancy; Dong, Qi; Huang, Hao

    2017-03-01

    Human brain functional networks are topologically organized with nontrivial connectivity characteristics such as small-worldness and densely linked hubs to support highly segregated and integrated information processing. However, how they emerge and change at very early developmental phases remains poorly understood. Here, we used resting-state functional MRI and voxel-based graph theory analysis to systematically investigate the topological organization of whole-brain networks in 40 infants aged around 31 to 42 postmenstrual weeks. The functional connectivity strength and heterogeneity increased significantly in primary motor, somatosensory, visual, and auditory regions, but much less in high-order default-mode and executive-control regions. The hub and rich-club structures in primary regions were already present at around 31 postmenstrual weeks and exhibited remarkable expansions with age, accompanied by increased local clustering and shortest path length, indicating a transition from a relatively random to a more organized configuration. Moreover, multivariate pattern analysis using support vector regression revealed that individual brain maturity of preterm babies could be predicted by the network connectivity patterns. Collectively, we highlighted a gradually enhanced functional network segregation manner in the third trimester, which is primarily driven by the rapid increases of functional connectivity of the primary regions, providing crucial insights into the topological development patterns prior to birth. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma

    PubMed Central

    Salaün, Mathieu; Peng, Jing; Hensley, Harvey H.; Roder, Navid; Flieder, Douglas B.; Houlle-Crépin, Solène; Abramovici-Roels, Olivia; Sabourin, Jean-Christophe; Thiberville, Luc; Clapper, Margie L.

    2015-01-01

    Introduction Several matrix metalloproteinases (MMPs) are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging. Objective To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma. Methods K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT) and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors. Results In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27), but in none of the non-invasive (0/4) (p=0.001). Conclusion MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer. PMID:26193700

  18. Targeted Sos1 deletion reveals its critical role in early T-cell development

    PubMed Central

    Kortum, Robert L.; Sommers, Connie L.; Alexander, Clayton P.; Pinski, John M.; Li, Wenmei; Grinberg, Alex; Lee, Jan; Love, Paul E.; Samelson, Lawrence E.

    2011-01-01

    Activation of the small G protein Ras is required for thymocyte differentiation. In thymocytes, Ras is activated by the Ras guanine exchange factors (RasGEFs) Sos1, Sos2, and RasGRP1. We report the development of a floxed allele of sos1 to assess the role of Sos1 during thymocyte development. Sos1 was required for pre–T-cell receptor (pre-TCR)– but not TCR-stimulated developmental signals. Sos1 deletion led to a partial block at the DN-to-DP transition. Sos1-deficient thymocytes showed reduced pre-TCR–stimulated proliferation, differentiation, and ERK phosphorylation. In contrast, TCR-stimulated positive selection, and negative selection under strong stimulatory conditions, remained intact in Sos1-deficient mice. Comparison of RasGEF expression at different developmental stages showed that relative to Sos2 and RasGRP1, Sos1 is most abundant in DN thymocytes, but least abundant in DP thymocytes. These data reveal that Sos1 is uniquely positioned to affect signal transduction early in thymocyte development. PMID:21746917

  19. Reconstruction of the vertebrate ancestral genome reveals dynamic genome reorganization in early vertebrates.

    PubMed

    Nakatani, Yoichiro; Takeda, Hiroyuki; Kohara, Yuji; Morishita, Shinichi

    2007-09-01

    Although several vertebrate genomes have been sequenced, little is known about the genome evolution of early vertebrates and how large-scale genomic changes such as the two rounds of whole-genome duplications (2R WGD) affected evolutionary complexity and novelty in vertebrates. Reconstructing the ancestral vertebrate genome is highly nontrivial because of the difficulty in identifying traces originating from the 2R WGD. To resolve this problem, we developed a novel method capable of pinning down remains of the 2R WGD in the human and medaka fish genomes using invertebrate tunicate and sea urchin genes to define ohnologs, i.e., paralogs produced by the 2R WGD. We validated the reconstruction using the chicken genome, which was not considered in the reconstruction step, and observed that many ancestral proto-chromosomes were retained in the chicken genome and had one-to-one correspondence to chicken microchromosomes, thereby confirming the reconstructed ancestral genomes. Our reconstruction revealed a contrast between the slow karyotype evolution after the second WGD and the rapid, lineage-specific genome reorganizations that occurred in the ancestral lineages of major taxonomic groups such as teleost fishes, amphibians, reptiles, and marsupials.

  20. Color blindness

    MedlinePlus

    Color deficiency; Blindness - color ... Color blindness occurs when there is a problem with the pigments in certain nerve cells of the eye that sense color. These cells are called cones. They are found ...

  1. Analysis of gene expression during parabolic flights reveals distinct early gravity responses in Arabidopsis roots.

    PubMed

    Aubry-Hivet, D; Nziengui, H; Rapp, K; Oliveira, O; Paponov, I A; Li, Y; Hauslage, J; Vagt, N; Braun, M; Ditengou, F A; Dovzhenko, A; Palme, K

    2014-01-01

    Plant roots are among most intensively studied biological systems in gravity research. Altered gravity induces asymmetric cell growth leading to root bending. Differential distribution of the phytohormone auxin underlies root responses to gravity, being coordinated by auxin efflux transporters from the PIN family. The objective of this study was to compare early transcriptomic changes in roots of Arabidopsis thaliana wild type, and pin2 and pin3 mutants under parabolic flight conditions and to correlate these changes to auxin distribution. Parabolic flights allow comparison of transient 1-g, hypergravity and microgravity effects in living organisms in parallel. We found common and mutation-related genes differentially expressed in response to transient microgravity phases. Gene ontology analysis of common genes revealed lipid metabolism, response to stress factors and light categories as primarily involved in response to transient microgravity phases, suggesting that fundamental reorganisation of metabolic pathways functions upstream of a further signal mediating hormonal network. Gene expression changes in roots lacking the columella-located PIN3 were stronger than in those deprived of the epidermis and cortex cell-specific PIN2. Moreover, repetitive exposure to microgravity/hypergravity and gravity/hypergravity flight phases induced an up-regulation of auxin responsive genes in wild type and pin2 roots, but not in pin3 roots, suggesting a critical function of PIN3 in mediating auxin fluxes in response to transient microgravity phases. Our study provides important insights towards understanding signal transduction processes in transient microgravity conditions by combining for the first time the parabolic flight platform with the transcriptome analysis of different genetic mutants in the model plant, Arabidopsis. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

  2. Kinetic isotope effects reveal early transition state of protein lysine methyltransferase SET8

    PubMed Central

    Linscott, Joshua A.; Kapilashrami, Kanishk; Wang, Zhen; Senevirathne, Chamara; Bothwell, Ian R.; Blum, Gil; Luo, Minkui

    2016-01-01

    Protein lysine methyltransferases (PKMTs) catalyze the methylation of protein substrates, and their dysregulation has been linked to many diseases, including cancer. Accumulated evidence suggests that the reaction path of PKMT-catalyzed methylation consists of the formation of a cofactor(cosubstrate)–PKMT–substrate complex, lysine deprotonation through dynamic water channels, and a nucleophilic substitution (SN2) transition state for transmethylation. However, the molecular characters of the proposed process remain to be elucidated experimentally. Here we developed a matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) method and corresponding mathematic matrix to determine precisely the ratios of isotopically methylated peptides. This approach may be generally applicable for examining the kinetic isotope effects (KIEs) of posttranslational modifying enzymes. Protein lysine methyltransferase SET8 is the sole PKMT to monomethylate histone 4 lysine 20 (H4K20) and its function has been implicated in normal cell cycle progression and cancer metastasis. We therefore implemented the MS-based method to measure KIEs and binding isotope effects (BIEs) of the cofactor S-adenosyl-l-methionine (SAM) for SET8-catalyzed H4K20 monomethylation. A primary intrinsic 13C KIE of 1.04, an inverse intrinsic α-secondary CD3 KIE of 0.90, and a small but statistically significant inverse CD3 BIE of 0.96, in combination with computational modeling, revealed that SET8-catalyzed methylation proceeds through an early, asymmetrical SN2 transition state with the C-N and C-S distances of 2.35–2.40 Å and 2.00–2.05 Å, respectively. This transition state is further supported by the KIEs, BIEs, and steady-state kinetics with the SAM analog Se-adenosyl-l-selenomethionine (SeAM) as a cofactor surrogate. The distinct transition states between protein methyltransferases present the opportunity to design selective transition-state analog inhibitors. PMID

  3. Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT)

    PubMed Central

    2013-01-01

    Background Preliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer’s disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers. Methods/design In this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined. Discussion If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion. Trial registration Current Controlled Trials ISRCTN21027481 PMID:23710796

  4. Altered Evoked Gamma-Band Responses Reveal Impaired Early Visual Processing in ADHD Children

    ERIC Educational Resources Information Center

    Lenz, Daniel; Krauel, Kerstin; Flechtner, Hans-Henning; Schadow, Jeanette; Hinrichs, Hermann; Herrmann, Christoph S.

    2010-01-01

    Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90 ms after visual stimulation in human EEG, have…

  5. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

    DOE PAGES

    Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz; ...

    2017-03-22

    Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

  6. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

    SciTech Connect

    Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz

    Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

  7. A diminutive perinate European Enantiornithes reveals an asynchronous ossification pattern in early birds

    DOE PAGES

    Knoll, Fabien; Chiappe, Luis M.; Sanchez, Sophie; ...

    2018-03-05

    Fossils of juvenile Mesozoic birds provide insight into the early evolution of avian development, however such fossils are rare. The analysis of the ossification sequence in these early-branching birds has the potential to address important questions about their comparative developmental biology and to help understand their morphological evolution and ecological differentiation. Here we report on an early juvenile enantiornithine specimen from the Early Cretaceous of Europe, which sheds new light on the osteogenesis in this most species-rich clade of Mesozoic birds. Consisting of a nearly complete skeleton, it is amongst the smallest known Mesozoic avian fossils representing post-hatching stages ofmore » development. Finally, comparisons between this new specimen and other known early juvenile enantiornithines support a clade-wide asynchronous pattern of osteogenesis in the sternum and the vertebral column, and strongly indicate that the hatchlings of these phylogenetically basal birds varied greatly in size and tempo of skeletal maturation.« less

  8. A diminutive perinate European Enantiornithes reveals an asynchronous ossification pattern in early birds

    SciTech Connect

    Knoll, Fabien; Chiappe, Luis M.; Sanchez, Sophie

    Fossils of juvenile Mesozoic birds provide insight into the early evolution of avian development, however such fossils are rare. The analysis of the ossification sequence in these early-branching birds has the potential to address important questions about their comparative developmental biology and to help understand their morphological evolution and ecological differentiation. Here we report on an early juvenile enantiornithine specimen from the Early Cretaceous of Europe, which sheds new light on the osteogenesis in this most species-rich clade of Mesozoic birds. Consisting of a nearly complete skeleton, it is amongst the smallest known Mesozoic avian fossils representing post-hatching stages ofmore » development. Finally, comparisons between this new specimen and other known early juvenile enantiornithines support a clade-wide asynchronous pattern of osteogenesis in the sternum and the vertebral column, and strongly indicate that the hatchlings of these phylogenetically basal birds varied greatly in size and tempo of skeletal maturation.« less

  9. A diminutive perinate European Enantiornithes reveals an asynchronous ossification pattern in early birds.

    PubMed

    Knoll, Fabien; Chiappe, Luis M; Sanchez, Sophie; Garwood, Russell J; Edwards, Nicholas P; Wogelius, Roy A; Sellers, William I; Manning, Phillip L; Ortega, Francisco; Serrano, Francisco J; Marugán-Lobón, Jesús; Cuesta, Elena; Escaso, Fernando; Sanz, Jose Luis

    2018-03-05

    Fossils of juvenile Mesozoic birds provide insight into the early evolution of avian development, however such fossils are rare. The analysis of the ossification sequence in these early-branching birds has the potential to address important questions about their comparative developmental biology and to help understand their morphological evolution and ecological differentiation. Here we report on an early juvenile enantiornithine specimen from the Early Cretaceous of Europe, which sheds new light on the osteogenesis in this most species-rich clade of Mesozoic birds. Consisting of a nearly complete skeleton, it is amongst the smallest known Mesozoic avian fossils representing post-hatching stages of development. Comparisons between this new specimen and other known early juvenile enantiornithines support a clade-wide asynchronous pattern of osteogenesis in the sternum and the vertebral column, and strongly indicate that the hatchlings of these phylogenetically basal birds varied greatly in size and tempo of skeletal maturation.

  10. Large-scale Metabolomic Analysis Reveals Potential Biomarkers for Early Stage Coronary Atherosclerosis.

    PubMed

    Gao, Xueqin; Ke, Chaofu; Liu, Haixia; Liu, Wei; Li, Kang; Yu, Bo; Sun, Meng

    2017-09-18

    Coronary atherosclerosis (CAS) is the pathogenesis of coronary heart disease, which is a prevalent and chronic life-threatening disease. Initially, this disease is not always detected until a patient presents with seriously vascular occlusion. Therefore, new biomarkers for appropriate and timely diagnosis of early CAS is needed for screening to initiate therapy on time. In this study, we used an untargeted metabolomics approach to identify potential biomarkers that could enable highly sensitive and specific CAS detection. Score plots from partial least-squares discriminant analysis clearly separated early-stage CAS patients from controls. Meanwhile, the levels of 24 metabolites increased greatly and those of 18 metabolites decreased markedly in early CAS patients compared with the controls, which suggested significant metabolic dysfunction in phospholipid, sphingolipid, and fatty acid metabolism in the patients. Furthermore, binary logistic regression showed that nine metabolites could be used as a combinatorial biomarker to distinguish early-stage CAS patients from controls. The panel of nine metabolites was then tested with an independent cohort of samples, which also yielded satisfactory diagnostic accuracy (AUC = 0.890). In conclusion, our findings provide insight into the pathological mechanism of early-stage CAS and also supply a combinatorial biomarker to aid clinical diagnosis of early-stage CAS.

  11. Proton magnetic resonance spectroscopy (1H-MRS) reveals the presence of elevated myo-inositol in the occipital cortex of blind subjects.

    PubMed

    Bernabeu, Angela; Alfaro, Arantxa; García, Milagros; Fernández, Eduardo

    2009-10-01

    This paper is addressed to investigate whether proton magnetic resonance spectroscopy ((1)H-MRS) may provide the means to investigate changes associated to alterations of neural activity and sensory experience in the blind. We examined the relationships between different brain metabolite levels in 10 blind volunteers and 10 sighted subjects matched for age and gender. Adjusted levels of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), glutamate/glutamine (Glx) and myo-inositol (mIno) in the occipital cortex region were quantified in the water-suppressed spectrum using the AMARES estimation algorithms. An unpaired two-tailed t-test was used to determine any significant difference in metabolite ratios. Our results show that none of the blind volunteers presented atrophy or any other MRI detectable degenerative change of the occipital cortex. The main finding was a significant increase of myo-inositol (mIno), a glial marker, in blind subjects compared to sighted controls. This simple sugar-like molecule can be found mainly within astrocytes, and cannot cross the blood-brain barrier. Therefore its increase could reflect glial proliferation or an increase in glial cell size. These results show that (1)H-MRS may help to understand the complex mechanisms involved in brain plasticity and suggest an active role of glial cells in the reorganization of the brain in response to visual deprivation.

  12. Early metal-silicate differentiation during planetesimal formation revealed by acapulcoite and lodranite meteorites

    NASA Astrophysics Data System (ADS)

    Dhaliwal, Jasmeet K.; Day, James M. D.; Corder, Christopher A.; Tait, Kim T.; Marti, Kurt; Assayag, Nelly; Cartigny, Pierre; Rumble, Doug; Taylor, Lawrence A.

    2017-11-01

    In order to establish the role and expression of silicate-metal fractionation in early planetesimal bodies, we have conducted a highly siderophile element (HSE: Os, Ir, Ru, Pt, Pd, Re) abundance and 187Re-187Os study of acapulcoite-lodranite meteorites. These data are reported with new petrography, mineral chemistry, bulk-rock major and trace element geochemistry, and oxygen isotopes for Acapulco, Allan Hills (ALHA) 81187, Meteorite Hills (MET) 01195, Northwest Africa (NWA) 2871, NWA 4833, NWA 4875, NWA 7474 and two examples of transitional acapulcoite-lodranites, Elephant Moraine (EET) 84302 and Graves Nunataks (GRA) 95209. These data support previous studies that indicate that these meteorites are linked to the same parent body and exhibit limited degrees (<2-7%) of silicate melt removal. New HSE and osmium isotope data demonstrate broadly chondritic relative and absolute abundances of these elements in acapulcoites, lower absolute abundances in lodranites and elevated (>2 × CI chondrite) HSE abundances in transitional acapulcoite-lodranite meteorites (EET 84302, GRA 95209). All of the meteorites have chondritic Re/Os with measured 187Os/188Os ratios of 0.1271 ± 0.0040 (2 St. Dev.). These geochemical characteristics imply that the precursor material of the acapulcoites and lodranites was broadly chondritic in composition, and were then heated and subject to melting of metal and sulfide in the Fe-Ni-S system. This resulted in metallic melt removal and accumulation to form lodranites and transitional acapulcoite-lodranites. There is considerable variation in the absolute abundances of the HSE, both among samples and between aliquots of the same sample, consistent with both inhomogeneous distribution of HSE-rich metal, and of heterogeneous melting and incomplete mixing of silicate material within the acapulcoite-lodranite parent body. Oxygen isotope data for acapulcoite-lodranites are also consistent with inhomogeneous melting and mixing of accreted components

  13. Barium distributions in teeth reveal early-life dietary transitions in primates.

    PubMed

    Austin, Christine; Smith, Tanya M; Bradman, Asa; Hinde, Katie; Joannes-Boyau, Renaud; Bishop, David; Hare, Dominic J; Doble, Philip; Eskenazi, Brenda; Arora, Manish

    2013-06-13

    Early-life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations. Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth. Uncovering early-life dietary history in fossils is hampered by the absence of prospectively validated biomarkers that are not modified during fossilization. Here we show that large dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother's milk through the weaning process. We also document dietary transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, indicating an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history.

  14. Dynamic Locomotor Capabilities Revealed by Early Dinosaur Trackmakers from Southern Africa

    PubMed Central

    Wilson, Jeffrey A.; Marsicano, Claudia A.; Smith, Roger M. H.

    2009-01-01

    Background A new investigation of the sedimentology and ichnology of the Early Jurassic Moyeni tracksite in Lesotho, southern Africa has yielded new insights into the behavior and locomotor dynamics of early dinosaurs. Methodology/Principal Findings The tracksite is an ancient point bar preserving a heterogeneous substrate of varied consistency and inclination that includes a ripple-marked riverbed, a bar slope, and a stable algal-matted bar top surface. Several basal ornithischian dinosaurs and a single theropod dinosaur crossed its surface within days or perhaps weeks of one another, but responded to substrate heterogeneity differently. Whereas the theropod trackmaker accommodated sloping and slippery surfaces by gripping the substrate with its pedal claws, the basal ornithischian trackmakers adjusted to the terrain by changing between quadrupedal and bipedal stance, wide and narrow gauge limb support (abduction range = 31°), and plantigrade and digitigrade foot posture. Conclusions/Significance The locomotor adjustments coincide with changes in substrate consistency along the trackway and appear to reflect ‘real time’ responses to a complex terrain. It is proposed that these responses foreshadow important locomotor transformations characterizing the later evolution of the two main dinosaur lineages. Ornithischians, which shifted from bipedal to quadrupedal posture at least three times in their evolutionary history, are shown to have been capable of adopting both postures early in their evolutionary history. The substrate-gripping behavior demonstrated by the early theropod, in turn, is consistent with the hypothesized function of pedal claws in bird ancestors. PMID:19806213

  15. Dynamic locomotor capabilities revealed by early dinosaur trackmakers from southern Africa.

    PubMed

    Wilson, Jeffrey A; Marsicano, Claudia A; Smith, Roger M H

    2009-10-06

    A new investigation of the sedimentology and ichnology of the Early Jurassic Moyeni tracksite in Lesotho, southern Africa has yielded new insights into the behavior and locomotor dynamics of early dinosaurs. The tracksite is an ancient point bar preserving a heterogeneous substrate of varied consistency and inclination that includes a ripple-marked riverbed, a bar slope, and a stable algal-matted bar top surface. Several basal ornithischian dinosaurs and a single theropod dinosaur crossed its surface within days or perhaps weeks of one another, but responded to substrate heterogeneity differently. Whereas the theropod trackmaker accommodated sloping and slippery surfaces by gripping the substrate with its pedal claws, the basal ornithischian trackmakers adjusted to the terrain by changing between quadrupedal and bipedal stance, wide and narrow gauge limb support (abduction range = 31 degrees ), and plantigrade and digitigrade foot posture. The locomotor adjustments coincide with changes in substrate consistency along the trackway and appear to reflect 'real time' responses to a complex terrain. It is proposed that these responses foreshadow important locomotor transformations characterizing the later evolution of the two main dinosaur lineages. Ornithischians, which shifted from bipedal to quadrupedal posture at least three times in their evolutionary history, are shown to have been capable of adopting both postures early in their evolutionary history. The substrate-gripping behavior demonstrated by the early theropod, in turn, is consistent with the hypothesized function of pedal claws in bird ancestors.

  16. Barium distributions in teeth reveal early life dietary transitions in primates

    PubMed Central

    Austin, Christine; Smith, Tanya M.; Bradman, Asa; Hinde, Katie; Joannes-Boyau, Renaud; Bishop, David; Hare, Dominic J.; Doble, Philip; Eskenazi, Brenda; Arora, Manish

    2013-01-01

    Early life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations1,2. Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth3. Uncovering early life dietary history in fossils is hampered by the absence of prospectively-validated biomarkers that are not modified during fossilisation4. Here we show that major dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively-recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother’s milk and through the weaning process. We also document transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, suggesting an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history. PMID:23698370

  17. The TESIS Project: Revealing Massive Early-Type Galaxies at z > 1

    NASA Astrophysics Data System (ADS)

    Saracco, P.; Longhetti, M.; Severgnini, P.; Della Ceca, R.; Braito, V.; Bender, R.; Drory, N.; Feulner, G.; Hopp, U.; Mannucci, F.; Maraston, C.

    How and when present-day massive early-type galaxies built up and what type of evolution has characterized their growth (star formation and/or merging) still remain open issues. The different competing scenarios of galaxy formation predict much different properties of early-type galaxies at z > 1. The "monolithic" collapse predicts that massive spheroids formed at high redshift (z > 2.5-3) and that their comoving density is constant at z < 2.5-3 since they evolve only in luminosity. On the contrary, in the hierarchical scenario massive spheroids are built up through subsequent mergers reaching their final masses at z < 1.5 [3,5]. As a consequence, massive systems are very rare at z > 1, their comoving density decreases from z = 0 to z ~ 1.5 and they should experience their last burst of star formation at z < 1.5, concurrent with the merging event(s) of their formation. These opposed predicted properties of early-types at z > 1 can be probed observationally once a well defined sample of massive early-types at z > 1 is available. We are constructing such a sample through a dedicated near-IR very low resolution (λ/Δλ≃50) spectroscopic survey (TNG EROs Spectroscopic Identification Survey, TESIS, [6]) of a complete sample of 30 bright (K < 18.5) Extremely Red Objects (EROs).

  18. Starch grains on human teeth reveal early broad crop diet in northern Peru

    PubMed Central

    Piperno, Dolores R.; Dillehay, Tom D.

    2008-01-01

    Previous research indicates that the Ñanchoc Valley in northern Peru was an important locus of early and middle Holocene human settlement, and that between 9200 and 5500 14C yr B.P. the valley inhabitants adopted major crop plants such as squash (Cucurbita moschata), peanuts (Arachis sp.), and cotton (Gossypium barbadense). We report here an examination of starch grains preserved in the calculus of human teeth from these sites that provides direct evidence for the early consumption of cultivated squash and peanuts along with two other major food plants not previously detected. Starch from the seeds of Phaseolus and Inga feuillei, the flesh of Cucurbita moschata fruits, and the nuts of Arachis was routinely present on numerous teeth that date to between 8210 and 6970 14C yr B.P. Early plant diets appear to have been diverse and stable through time and were rich in cultivated foods typical of later Andean agriculture. Our data provide early archaeological evidence for Phaseolus beans and I. feuillei, an important tree crop, and indicate that effective food production systems that contributed significant dietary inputs were present in the Ñanchoc region by 8000 14C yr B.P. Starch grain studies of dental remains document plants and edible parts of them not normally preserved in archaeological records and can assume primary roles as direct indicators of ancient human diets and agriculture. PMID:19066222

  19. Transcriptome Analysis of Honeybee (Apis Mellifera) Haploid and Diploid Embryos Reveals Early Zygotic Transcription during Cleavage

    PubMed Central

    Pires, Camilla Valente; Freitas, Flávia Cristina de Paula; Cristino, Alexandre S.; Dearden, Peter K.; Simões, Zilá Luz Paulino

    2016-01-01

    In honeybees, the haplodiploid sex determination system promotes a unique embryogenesis process wherein females develop from fertilized eggs and males develop from unfertilized eggs. However, the developmental strategies of honeybees during early embryogenesis are virtually unknown. Similar to most animals, the honeybee oocytes are supplied with proteins and regulatory elements that support early embryogenesis. As the embryo develops, the zygotic genome is activated and zygotic products gradually replace the preloaded maternal material. The analysis of small RNA and mRNA libraries of mature oocytes and embryos originated from fertilized and unfertilized eggs has allowed us to explore the gene expression dynamics in the first steps of development and during the maternal-to-zygotic transition (MZT). We localized a short sequence motif identified as TAGteam motif and hypothesized to play a similar role in honeybees as in fruit flies, which includes the timing of early zygotic expression (MZT), a function sustained by the presence of the zelda ortholog, which is the main regulator of genome activation. Predicted microRNA (miRNA)-target interactions indicated that there were specific regulators of haploid and diploid embryonic development and an overlap of maternal and zygotic gene expression during the early steps of embryogenesis. Although a number of functions are highly conserved during the early steps of honeybee embryogenesis, the results showed that zygotic genome activation occurs earlier in honeybees than in Drosophila based on the presence of three primary miRNAs (pri-miRNAs) (ame-mir-375, ame-mir-34 and ame-mir-263b) during the cleavage stage in haploid and diploid embryonic development. PMID:26751956

  20. Obsessive-compulsive symptoms in a randomized, double-blind study with olanzapine or risperidone in young patients with early psychosis.

    PubMed

    van Nimwegen, Lonneke; de Haan, Lieuwe; van Beveren, Nico; Laan, Winfried; van den Brink, Wim; Linszen, Don

    2008-04-01

    The prevalence of obsessive-compulsive symptoms (OCS) in patients with schizophrenia is relatively high. Antipsychotics have been found to influence OCS. To determine whether induction or severity of OCS differs during treatment with olanzapine or risperidone in young patients with early psychosis. One hundred twenty-two patients with a Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder were randomized in a double-blind design to groups of 6 weeks' treatment with olanzapine (n = 59) or risperidone (n = 63), with a mean dose of 11.3 mg olanzapine and 3.0 mg risperidone at 6 weeks. Primary outcome measures were the mean baseline-to-endpoint change in total score on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Treatment with olanzapine was associated with greater decreases in Y-BOCS total score than treatment with risperidone in total group (N = 122: -2.2 vs -0.3, z = -2.651, P < 0.01), in patients with baseline Y-BOCS total score greater than 0 (n = 58: -5.1 vs -0.4, z = -2.717, P < 0.01), and in patients with baseline Y-BOCS total score greater than 10 (n = 29: -7.1 vs -0.6, z = -2.138, P = 0.032). In this randomized, 6-week, double-blind trial, we found a significant and clinically relevant difference in decrease in Y-BOCS scores favoring olanzapine compared with risperidone.

  1. The Effect of Ginger on Breast Milk Volume in the Early Postpartum Period: A Randomized, Double-Blind Controlled Trial.

    PubMed

    Paritakul, Panwara; Ruangrongmorakot, Kasem; Laosooksathit, Wipada; Suksamarnwong, Maysita; Puapornpong, Pawin

    2016-09-01

    In Thailand, ginger is a popular natural galactagogue among breastfeeding women. However, there has never been evidence to support the effectiveness of ginger in increasing the breast milk volume. To compare breast milk volume on the third and seventh day postpartum between lactating mothers who receive 500 mg dried ginger capsules twice daily with those receiving placebo. A randomized, double-blind controlled trial was conducted. Women who deliver a term baby were randomly assigned to receive dried ginger or placebo for 7 days postpartum. Breast milk volume was measured on third day postpartum using test weight method for a period of 24 hours and on seventh day postpartum using 1 hour milk production. We also compared the third day serum prolactin level between the two groups. Data from 63 women were available for analysis, 30 from the ginger group and 33 from the placebo group. The two groups were similar regarding baseline characteristics. Women in the ginger group have higher milk volume than the placebo group (191.0 ± 71.2 mL/day versus 135.0 ± 61.5 mL/day, p < 0.01). However, the seventh day milk volume in the ginger group does not differ from the placebo group (80.0 ± 58.5 mL versus 112.1 ± 91.6 mL, p = 0.24). The mean serum prolactin levels were similar in both groups (321.5 ± 131.8 ng/L in the ginger group, and 331.4 ± 100.7 ng/L in the placebo group, p = 0.74). No side effect was reported in this study. Ginger is a promising natural galactagogue to improve breast milk volume in the immediate postpartum period without any notable side effect.

  2. Revealing the origin of the cold ISM in massive early-type galaxies

    NASA Astrophysics Data System (ADS)

    Davis, T. A.; Alatalo, K.; Bureau, M.; Young, L.; Blitz, L.; Crocker, A.; Bayet, E.; Bois, M.; Bournaud, F.; Cappellari, M.; Davies, R. L.; Duc, P.-A.; de Zeeuw, P. T.; Emsellem, E.; Falcon-Barroso, J.; Khochfar, S.; Krajnovic, D.; Kuntschner, H.; Lablanche, P.-Y.; McDermid, R. M.; Morganti, R.; Naab, T.; Sarzi, M.; Scott, N.; Serra, P.; Weijmans, A.

    2013-07-01

    Recently, massive early-type galaxies have shed their red-and-dead moniker, thanks to the discovery that many host residual star formation. As part of the ATLAS-3D project, we have conducted a complete, volume-limited survey of the molecular gas in 260 local early-type galaxies with the IRAM-30m telescope and the CARMA interferometer, in an attempt to understand the fuel powering this star formation. We find that around 22% of early-type galaxies in the local volume host molecular gas reservoirs. This detection rate is independent of galaxy luminosity and environment. Here we focus on how kinematic misalignment measurements and gas-to-dust ratios can be used to put constraints on the origin of the cold ISM in these systems. The origin of the cold ISM seems to depend strongly on environment, with misaligned, dust poor gas (indicative of externally acquired material) being common in the field but completely absent in rich groups and in the Virgo cluster. Very massive galaxies also appear to be devoid of accreted gas. This suggests that in the field mergers and/or cold gas accretion dominate the gas supply, while in clusters internal secular processes become more important. This implies that environment has a strong impact on the cold gas properties of ETGs.

  3. Bird-like anatomy, posture, and behavior revealed by an early jurassic theropod dinosaur resting trace.

    PubMed

    Milner, Andrew R C; Harris, Jerald D; Lockley, Martin G; Kirkland, James I; Matthews, Neffra A

    2009-01-01

    Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. Here we describe a well-preserved theropod trackway in a Lower Jurassic ( approximately 198 million-year-old) lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods.

  4. Exome Sequencing Frequently Reveals the Cause of Early-Onset Chronic Kidney Disease

    PubMed Central

    Vivante, Asaf; Hildebrandt, Friedhelm

    2016-01-01

    The primary causes of chronic kidney disease (CKD) in children differ from those of adult onset CKD. In the United States the most common diagnostic groups of CKD that manifests before 25 years of age are: i) congenital anomalies of the kidneys and urinary tract (CAKUT) (49.1%), ii) steroid-resistant nephrotic syndrome (SRNS) (10.4%), iii) chronic glomerulonephritis (8.1%), and iv) renal cystic ciliopathies (5.3 %), encompassing >70% of CKD together. Recent findings suggest that early-onset CKD is caused by mutations in any one of over 200 different monogenic genes. High-throughput sequencing has very recently rendered identification of causative mutations in this high number of genes feasible. Molecular genetic diagnostics in early onset-CKD (before the age of 25 years) will, i) provide patients and families with a molecular genetic diagnosis, ii) generate new insights into diseases mechanisms, iii) allow etiology-based classification of patient cohorts for clinical studies and, iv) may have consequences for personalized treatment and prevention of CKD. In this review, we will discuss the implications of next-generation sequencing for clinical genetic diagnostics and discovery of novel genes in early-onset CKD. We also delineate the resulting opportunities for deciphering disease mechanisms and therapeutic implications. PMID:26750453

  5. Bird-like anatomy, posture, and behavior revealed by an early jurassic theropod dinosaur resting trace

    USGS Publications Warehouse

    Milner, Andrew R.C.; Harris, J.D.; Lockley, M.G.; Kirkland, J.I.; Matthews, N.A.

    2009-01-01

    Background: Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. Methodology/Principal Findings: Here we describe a well-preserved theropod trackway in a Lower Jurassic (???198 millionyear- old) lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. Conclusions/Significance: The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods.

  6. Bird-Like Anatomy, Posture, and Behavior Revealed by an Early Jurassic Theropod Dinosaur Resting Trace

    PubMed Central

    Milner, Andrew R. C.; Harris, Jerald D.; Lockley, Martin G.; Kirkland, James I.; Matthews, Neffra A.

    2009-01-01

    Background Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. Methodology/Principal Findings Here we describe a well-preserved theropod trackway in a Lower Jurassic (∼198 million-year-old) lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. Conclusions/Significance The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods. PMID:19259260

  7. High versus low energy administration in the early phase of acute pancreatitis (GOULASH trial): protocol of a multicentre randomised double-blind clinical trial.

    PubMed

    Márta, Katalin; Szabó, Anikó N; Pécsi, Dániel; Varjú, Péter; Bajor, Judit; Gódi, Szilárd; Sarlós, Patrícia; Mikó, Alexandra; Szemes, Kata; Papp, Mária; Tornai, Tamás; Vincze, Áron; Márton, Zsolt; Vincze, Patrícia A; Lankó, Erzsébet; Szentesi, Andrea; Molnár, Tímea; Hágendorn, Roland; Faluhelyi, Nándor; Battyáni, István; Kelemen, Dezső; Papp, Róbert; Miseta, Attila; Verzár, Zsófia; Lerch, Markus M; Neoptolemos, John P; Sahin-Tóth, Miklós; Petersen, Ole H; Hegyi, Péter

    2017-09-14

    Acute pancreatitis (AP) is an inflammatory disease with no specific treatment. Mitochondrial injury followed by ATP depletion in both acinar and ductal cells is a recently discovered early event in its pathogenesis. Importantly, preclinical research has shown that intracellular ATP delivery restores the physiological function of the cells and protects from cell injury, suggesting that restoration of energy levels in the pancreas is therapeutically beneficial. Despite several high quality experimental observations in this area, no randomised trials have been conducted to date to address the requirements for energy intake in the early phase of AP. This is a randomised controlled two-arm double-blind multicentre trial. Patients with AP will be randomly assigned to groups A (30 kcal/kg/day energy administration starting within 24 hours of hospital admission) or B (low energy administration during the first 72 hours of hospital admission). Energy will be delivered by nasoenteric tube feeding with additional intravenous glucose supplementation or total parenteral nutrition if necessary. A combination of multiorgan failure for more than 48 hours and mortality is defined as the primary endpoint, whereas several secondary endpoints such as length of hospitalisation or pain will be determined to elucidate more detailed differences between the groups. The general feasibility, safety and quality checks required for high quality evidence will be adhered to. The study has been approved by the relevant organisation, the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (55961-2/2016/EKU). This study will provide evidence as to whether early high energy nutritional support is beneficial in the clinical management of AP. The results of this trial will be published in an open access way and disseminated among medical doctors. The trial has been registered at the ISRCTN (ISRTCN 63827758). © Article author(s) (or their employer(s) unless

  8. High versus low energy administration in the early phase of acute pancreatitis (GOULASH trial): protocol of a multicentre randomised double-blind clinical trial

    PubMed Central

    Márta, Katalin; Szabó, Anikó N; Pécsi, Dániel; Varjú, Péter; Bajor, Judit; Gódi, Szilárd; Sarlós, Patrícia; Mikó, Alexandra; Szemes, Kata; Papp, Mária; Tornai, Tamás; Vincze, Áron; Márton, Zsolt; Vincze, Patrícia A; Lankó, Erzsébet; Szentesi, Andrea; Molnár, Tímea; Hágendorn, Roland; Faluhelyi, Nándor; Battyáni, István; Kelemen, Dezső; Papp, Róbert; Miseta, Attila; Verzár, Zsófia; Lerch, Markus M; Neoptolemos, John P; Sahin-Tóth, Miklós; Petersen, Ole H; Hegyi, Péter

    2017-01-01

    Introduction Acute pancreatitis (AP) is an inflammatory disease with no specific treatment. Mitochondrial injury followed by ATP depletion in both acinar and ductal cells is a recently discovered early event in its pathogenesis. Importantly, preclinical research has shown that intracellular ATP delivery restores the physiological function of the cells and protects from cell injury, suggesting that restoration of energy levels in the pancreas is therapeutically beneficial. Despite several high quality experimental observations in this area, no randomised trials have been conducted to date to address the requirements for energy intake in the early phase of AP. Methods/design This is a randomised controlled two-arm double-blind multicentre trial. Patients with AP will be randomly assigned to groups A (30 kcal/kg/day energy administration starting within 24 hours of hospital admission) or B (low energy administration during the first 72 hours of hospital admission). Energy will be delivered by nasoenteric tube feeding with additional intravenous glucose supplementation or total parenteral nutrition if necessary. A combination of multiorgan failure for more than 48 hours and mortality is defined as the primary endpoint, whereas several secondary endpoints such as length of hospitalisation or pain will be determined to elucidate more detailed differences between the groups. The general feasibility, safety and quality checks required for high quality evidence will be adhered to. Ethics and dissemination The study has been approved by the relevant organisation, the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (55961-2/2016/EKU). This study will provide evidence as to whether early high energy nutritional support is beneficial in the clinical management of AP. The results of this trial will be published in an open access way and disseminated among medical doctors. Trial registration The trial has been registered at the ISRCTN

  9. A randomized, double-blind, placebo-controlled trial of safinamide as add-on therapy in early Parkinson's disease patients.

    PubMed

    Stocchi, Fabrizio; Borgohain, Rupam; Onofrj, Marco; Schapira, Anthony H V; Bhatt, Mohit; Lucini, Valentina; Giuliani, Rodolfo; Anand, Ravi

    2012-01-01

    Safinamide is an α-aminoamide with both dopaminergic and nondopaminergic mechanisms of action evaluated as an add-on to dopamine agonist (DA) therapy in early-stage PD. In this 24-week, double-blind study, patients with early PD receiving a stable dose of a single DA were randomized to once-daily safinamide 100 mg, safinamide 200 mg, or placebo. The primary efficacy variable was UPDRS part III (motor examination) total score. Analysis was hierarchical: 200 mg of safinamide versus placebo was tested first; the success of safinamide 100 mg versus placebo was contingent on this. Two hundred sixty-nine patients received safinamide 100 mg (n = 90), safinamide 200 mg (n = 89), or placebo (n = 90); 70, 81, and 81 patients, respectively, completed the study. Mean improvements from baseline to week 24 in UPDRS III total scores were -3.90 for safinamide 200 mg, -6.0 for safinamide 100 mg and -3.60 for placebo. The difference between safinamide 200 mg and placebo was not significant [point estimate: -0.4; 95% confidence interval (CI): -2.3-1.4; P = 0.6504]. Although the difference between 100 mg/day and placebo was significant (point estimate: -1.9; 95% CI: -3.7 to -0.1; P = 0.0419), these results are considered exploratory. No clinically meaningful differences from placebo were observed for any safety variables. This study did not demonstrate a significant improvement of the primary endpoint for safinamide 200 mg/day. Exploratory analysis of the primary endpoint for 100 mg/day demonstrated that the addition of safinamide to a stable dose of DA improves motor symptoms in early PD and warrants further investigation. Copyright © 2011 Movement Disorder Society.

  10. Effectiveness of Riluzole as a pharmacotherapeutic treatment option for early cervical myelopathy: a double-blinded, placebo-controlled randomised controlled trial.

    PubMed

    Rajasekaran, S; Aiyer, Siddharth N; Shetty, Ajoy Prasad; Kanna, Rishi Mugesh; Maheswaran, Anupama; Shetty, Janardhan Yerram

    2016-06-01

    To evaluate the effectiveness of Riluzole as a pharmacotherapeutic treatment option for early cervical myelopathy using clinical parameters and DTI analysis. Early cervical myelopathy cases with MJOA scores ≥13, were recruited for the double-blinded, placebo-controlled randomised control trial. Thirty cases with fifteen cases each in the test and placebo group were studied. Analysis was done using diffusion tensor imaging (DTI) and clinical evaluation, pre- and post-institution of sodium channel blocker Riluzole for a period of 1 month (50 mg twice daily). Placebo group was treated with Vitamin B complex tablets. Diffusion co-efficient fractional anisotrophy (FA), apparent diffusion co-efficient (ADC), volume ratio (VR), relative anisotrophy (RA) and Eigen vectors were calculated. Outcomes analysis was based on clinical scores of MJOA, Nurick grading, SF-12, NDI, and statistical analysis of DTI datametrics. The mean MJOA score was 15.6 (13-17) with no significant change in the test and control groups. The mean ADC, FA values were 1533.36 (1238-1779) and 494.36 (364-628) and changed to 1531.57 (1312-2091) and 484.86 (294-597), respectively, in the Riluzole group. However, the changes in the values of ADC, FA, and other co-efficients including VR, RA and eigenvectors in the two groups were not statistically significant. The functional scores in the SF-12 and NDI questionnaires did not change significantly. Our study did not show a significant change in the clinical outcome and DTI Indices with the use of Riluzole as a standalone pharmacotherapeutic agent for early cervical myelopathy. More studies may be needed to confirm the usefulness of Riluzole as a treatment option for cervical myelopathy.

  11. Benzoate, a D-amino acid oxidase inhibitor, for the treatment of early-phase Alzheimer disease: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Lin, Chieh-Hsin; Chen, Ping-Kun; Chang, Yue-Cune; Chuo, Liang-Jen; Chen, Yan-Syun; Tsai, Guochuan E; Lane, Hsien-Yuan

    2014-05-01

    N-methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission is vital for learning and memory. Hypofunction of NMDAR has been reported to play a role in the pathophysiology of Alzheimer disease (AD), particularly in the early phase. Enhancing NMDAR activation might be a novel treatment approach. One of the methods to enhance NMDAR activity is to raise the levels of NMDA coagonists by blocking their metabolism. This study examined the efficacy and safety of sodium benzoate, a D-amino acid oxidase inhibitor, for the treatment of amnestic mild cognitive impairment and mild AD. We conducted a randomized, double-blind, placebo-controlled trial in four major medical centers in Taiwan. Sixty patients with amnestic mild cognitive impairment or mild AD were treated with 250-750 mg/day of sodium benzoate or placebo for 24 weeks. Alzheimer's Disease Assessment Scale-cognitive subscale (the primary outcome) and global function (assessed by Clinician Interview Based Impression of Change plus Caregiver Input) were measured every 8 weeks. Additional cognition composite was measured at baseline and endpoint. Sodium benzoate produced a better improvement than placebo in Alzheimer's Disease Assessment Scale-cognitive subscale (p = .0021, .0116, and .0031 at week 16, week 24, and endpoint, respectively), additional cognition composite (p = .007 at endpoint) and Clinician Interview Based Impression of Change plus Caregiver Input (p = .015, .016, and .012 at week 16, week 24, and endpoint, respectively). Sodium benzoate was well-tolerated without evident side-effects. Sodium benzoate substantially improved cognitive and overall functions in patients with early-phase AD. The preliminary results show promise for D-amino acid oxidase inhibition as a novel approach for early dementing processes. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Impact of empiric nesiritide or milrinone infusion on early postoperative recovery after Fontan surgery: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Costello, John M; Dunbar-Masterson, Carolyn; Allan, Catherine K; Gauvreau, Kimberlee; Newburger, Jane W; McGowan, Francis X; Wessel, David L; Mayer, John E; Salvin, Joshua W; Dionne, Roger E; Laussen, Peter C

    2014-07-01

    We sought to determine whether empirical nesiritide or milrinone would improve the early postoperative course after Fontan surgery. We hypothesized that compared with milrinone or placebo, patients assigned to receive nesiritide would have improved early postoperative outcomes. In a single-center, randomized, double-blinded, placebo-controlled, multi-arm parallel-group clinical trial, patients undergoing primary Fontan surgery were assigned to receive nesiritide, milrinone, or placebo. A loading dose of study drug was administered on cardiopulmonary bypass followed by a continuous infusion for ≥12 hours and ≤5 days after cardiac intensive care unit admission. The primary outcome was days alive and out of the hospital within 30 days of surgery. Secondary outcomes included measures of cardiovascular function, renal function, resource use, and adverse events. Among 106 enrolled subjects, 35, 36, and 35 were randomized to the nesiritide, milrinone, and placebo groups, respectively, and all were analyzed based on intention to treat. Demographics, patient characteristics, and operative factors were similar among treatment groups. No significant treatment group differences were found for median days alive and out of the hospital within 30 days of surgery (nesiritide, 20 [minimum to maximum, 0-24]; milrinone, 18 [0-23]; placebo, 20 [0-23]; P=0.38). Treatment groups did not significantly differ in cardiac index, arrhythmias, peak lactate, inotropic scores, urine output, duration of mechanical ventilation, intensive care or chest tube drainage, or adverse events. Compared with placebo, empirical perioperative nesiritide or milrinone infusions are not associated with improved early clinical outcomes after Fontan surgery. http://www.clinicaltrials.gov. Unique identifier: NCT00543309. © 2014 American Heart Association, Inc.

  13. Attention Measures of Accuracy, Variability, and Fatigue Detect Early Response to Donepezil in Alzheimer's Disease: A Randomized, Double-blind, Placebo-Controlled Pilot Trial.

    PubMed

    Vila-Castelar, Clara; Ly, Jenny J; Kaplan, Lillian; Van Dyk, Kathleen; Berger, Jeffrey T; Macina, Lucy O; Stewart, Jennifer L; Foldi, Nancy S

    2018-04-09

    Donepezil is widely used to treat Alzheimer's disease (AD), but detecting early response remains challenging for clinicians. Acetylcholine is known to directly modulate attention, particularly under high cognitive conditions, but no studies to date test whether measures of attention under high load can detect early effects of donepezil. We hypothesized that load-dependent attention tasks are sensitive to short-term treatment effects of donepezil, while global and other domain-specific cognitive measures are not. This longitudinal, randomized, double-blind, placebo-controlled pilot trial (ClinicalTrials.gov Identifier: NCT03073876) evaluated 23 participants newly diagnosed with AD initiating de novo donepezil treatment (5 mg). After baseline assessment, participants were randomized into Drug (n = 12) or Placebo (n = 11) groups, and retested after approximately 6 weeks. Cognitive assessment included: (a) attention tasks (Foreperiod Effect, Attentional Blink, and Covert Orienting tasks) measuring processing speed, top-down accuracy, orienting, intra-individual variability, and fatigue; (b) global measures (Alzheimer's Disease Assessment Scale-Cognitive Subscale, Mini-Mental Status Examination, Dementia Rating Scale); and (c) domain-specific measures (memory, language, visuospatial, and executive function). The Drug but not the Placebo group showed benefits of treatment at high-load measures by preserving top-down accuracy, improving intra-individual variability, and averting fatigue. In contrast, other global or cognitive domain-specific measures could not detect treatment effects over the same treatment interval. The pilot-study suggests that attention measures targeting accuracy, variability, and fatigue under high-load conditions could be sensitive to short-term cholinergic treatment. Given the central role of acetylcholine in attentional function, load-dependent attentional measures may be valuable cognitive markers of early treatment response.

  14. Functional weight-bearing mobilization after Achilles tendon rupture enhances early healing response: a single-blinded randomized controlled trial.

    PubMed

    Valkering, Kars P; Aufwerber, Susanna; Ranuccio, Francesco; Lunini, Enricomaria; Edman, Gunnar; Ackermann, Paul W

    2017-06-01

    Functional weight-bearing mobilization may improve repair of Achilles tendon rupture (ATR), but the underlying mechanisms and outcome were unknown. We hypothesized that functional weight-bearing mobilization by means of increased metabolism could improve both early and long-term healing. In this prospective randomized controlled trial, patients with acute ATR were randomized to either direct post-operative functional weight-bearing mobilization (n = 27) in an orthosis or to non-weight-bearing (n = 29) plaster cast immobilization. During the first two post-operative weeks, 15°-30° of plantar flexion was allowed and encouraged in the functional weight-bearing mobilization group. At 2 weeks, patients in the non-weight-bearing cast immobilization group received a stiff orthosis, while the functional weight-bearing mobilization group continued with increased range of motion. At 6 weeks, all patients discontinued immobilization. At 2 weeks, healing metabolites and markers of procollagen type I (PINP) and III (PIIINP) were examined using microdialysis. At 6 and 12 months, functional outcome using heel-rise test was assessed. Healing tendons of both groups exhibited increased levels of metabolites glutamate, lactate, pyruvate, and of PIIINP (all p < 0.05). Patients in functional weight-bearing mobilization group demonstrated significantly higher concentrations of glutamate compared to the non-weight-bearing cast immobilization group (p = 0.045).The upregulated glutamate levels were significantly correlated with the concentrations of PINP (r = 0.5, p = 0.002) as well as with improved functional outcome at 6 months (r = 0.4; p = 0.014). Heel-rise tests at 6 and 12 months did not display any differences between the two groups. Functional weight-bearing mobilization enhanced the early healing response of ATR. In addition, early ankle range of motion was improved without the risk of Achilles tendon elongation and without altering long-term functional

  15. Rotigotine transdermal patch in Chinese patients with early Parkinson's disease: A randomized, double-blind, placebo-controlled pivotal study.

    PubMed

    Zhang, Zhen-Xin; Shang, Hui-Fang; Hu, Xingyue; Chen, Shengdi; Zhao, Zhongxin; Du, Xinlu; Surmann, Erwin; Bauer, Lars; Asgharnejad, Mahnaz

    2016-07-01

    Two phase3 studies (SP512; SP513) involving mostly Caucasian patients showed that rotigotine (≤8 mg/24 h) was efficacious and welltolerated in early-stage Parkinson's disease (PD). We report results from a phase 3 study (SP0914/NCT01646268) investigating rotigotine in Chinese patients with early-stage PD. Patients were randomized 1:1 to rotigotine or placebo, titrated over 1-4 weeks, maintained at optimal/maximum dose (≤8 mg/24 h) for 24 weeks. Primary efficacy variable: change in Unified Parkinson's Disease Rating Scale (UPDRS) II + III total score from Baseline to End-of-Maintenance. Secondary variables: UPDRS II + III responders (≥20% decrease in UPDRS II + III) and changes in UPDRS II (activities of daily living [ADL]) and III (motor examination) subscores. Of 247 patients randomized, 113/124 (91.1%) rotigotine- and 107/123 (87.0%) placebo-treated patients completed the study. mean (SD) age: 59.4 (10.2) years; time since PD diagnosis: 1.01 (1.22) years, 60.7% male. Rotigotine significantly improved UPDRS II + III total score (change from Baseline LSmean [95%CI] treatment difference, -4.82 [-7.18 to -2.45]; P < 0.0001). UPDRS II + III responder rates were higher with rotigotine (42.3% vs 22.3%; P = 0.0006). UPDRS II and III subscores improved with rotigotine (both subscores: P < 0.0005 vs. placebo). Most frequent adverse events (AEs): nausea (8.9% rotigotine, 3.3% placebo), dizziness (8.1%, 5.7%), pruritus (8.1%, 4.1%), somnolence (8.1%, 3.3%), erythema (6.5%, 1.6%), and vomiting (5.6%, 1.6%). Thirteen (5.3%) patients discontinued due to AEs (6 rotigotine, 7 placebo). Rotigotine was efficacious in Chinese patients with early-stage PD, providing benefits to control of ADL and motor function. Rotigotine was generally welltolerated, with similar AEs to those observed in Caucasian patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Reworked crustal of early Paleozoic WuYi Orogen revealed by receiver function data

    NASA Astrophysics Data System (ADS)

    Wei, Y.; Duan, Y.; Tian, X.; Zhao, Y.

    2017-12-01

    Intraplate orogenic belt, which occurs at the rigid and undeformable plate interiors, is a distinct new type of orogen rather than an interplate or plate marginal orogenic belt, whose deformation occurs exclusively at plate margins. Therefore, intraplate orogenic belts are the most obvious exception to the plate-tectonic paradigm, they are uncommon in Earth's history. The early Paleozoic Wuyi orogen in South China is one of the few examples of intraplate orogen, and is a key to understanding the process of intraplate orogenesis and global early Paleozoic geodynamics. In this study, we select teleseismic records from 45 mobile linear seismic stations deployed in Wuyi Mountain and 58 permanent stations setting in Jiangxi and Fujian provinces, from January 2011 to December 2012, and calculate the crustal thickness and average crustal Vp/Vs ratio using the H-κ stacking method. The main results include the following: 1) the crustal average Poission's ratio shows an increase tendency from land to sea, the interior of Wuyi orogen belt with an low ration less than 0.23, and the coastline with high ration which is up to 0.28, which indicate a very heterogeneous crustal structure and composition in Wuyi orogen and coast belt. 2) the crustal thickness ranges 28-34 km and shows a tendency of thinning from inland to coast in the region of SE China margin, which maight mean the eastern Eurasia lithospheric is extension and thinning induced by the subducted paleo-Pacific slab. To conclusion, we assume that Wuyi orogen experienced upper crustal thickening, lower crust and lithosphere delamination during the early Paleozoic orogeny, and lithosphere extension in Mesozoic. This research is founded by the Natural Science Foundation of China (41174052 and 41604048).

  17. Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study.

    PubMed

    Sikich, Linmarie; Frazier, Jean A; McClellan, Jon; Findling, Robert L; Vitiello, Benedetto; Ritz, Louise; Ambler, Denisse; Puglia, Madeline; Maloney, Ann E; Michael, Emily; De Jong, Sandra; Slifka, Karen; Noyes, Nancy; Hlastala, Stefanie; Pierson, Leslie; McNamara, Nora K; Delporto-Bedoya, Denise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

    2008-11-01

    Atypical (second-generation) antipsychotics are considered standard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder. However, the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated. This study compared the efficacy and safety of two second-generation antipsychotics (olanzapine and risperidone) with a first-generation antipsychotic (molindone) in the treatment of early-onset schizophrenia and schizoaffective disorder. This double-blind multisite trial randomly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine (2.5-20 mg/day), risperidone (0.5-6 mg/day), or molindone (10-140 mg/day, plus 1 mg/day of benztropine) for 8 weeks. The primary outcome was response to treatment, defined as a Clinical Global Impression (CGI) improvement score of 1 or 2 and >or=20% reduction in Positive and Negative Syndrome Scale (PANSS) total score after 8 weeks of treatment. In total, 119 youth were randomly assigned to treatment. Of these subjects, 116 received at least one dose of treatment and thus were available for analysis. No significant differences were found among treatment groups in response rates (molindone: 50%; olanzapine: 34%; risperidone: 46%) or magnitude of symptom reduction. Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia. Risperidone and olanzapine did not demonstrate superior efficacy over molindone for treating early-onset schizophrenia and schizoaffective disorder. Adverse effects were frequent but differed among medications. The results question the nearly exclusive use of second-generation antipsychotics to treat early-onset schizophrenia

  18. Early events in plant hypersensitive response leaves revealed by IR thermography

    NASA Astrophysics Data System (ADS)

    Boccara, Martine; Boue, Christine; De Paepe, Rosine; Boccara, Albert C.

    2001-10-01

    Infrared thermography is used to reveal the establishment of Erwinia amylovora harpin-induced hypersensitive response (HR) in Nicotiana sylvestris leaves. We observed a decrease in temperature (1-2 degree(s)C) in the harpin infiltrated zone, correlated with an increase in stomatal opening, strongly suggesting that the temperature decrease is due to higher transpiration rate. IRT experiments were conducted in a laboratory environment and could be widely applied for genotype screening and monitoring drug effects.

  19. Synchrotron Reveals Early Triassic Odd Couple: Injured Amphibian and Aestivating Therapsid Share Burrow

    PubMed Central

    Fernandez, Vincent; Abdala, Fernando; Carlson, Kristian J.; Cook, Della Collins; Rubidge, Bruce S.; Yates, Adam; Tafforeau, Paul

    2013-01-01

    Fossorialism is a beneficial adaptation for brooding, predator avoidance and protection from extreme climate. The abundance of fossilised burrow casts from the Early Triassic of southern Africa is viewed as a behavioural response by many tetrapods to the harsh conditions following the Permo-Triassic mass-extinction event. However, scarcity of vertebrate remains associated with these burrows leaves many ecological questions unanswered. Synchrotron scanning of a lithified burrow cast from the Early Triassic of the Karoo unveiled a unique mixed-species association: an injured temnospondyl amphibian (Broomistega) that sheltered in a burrow occupied by an aestivating therapsid (Thrinaxodon). The discovery of this rare rhinesuchid represents the first occurrence in the fossil record of a temnospondyl in a burrow. The amphibian skeleton shows signs of a crushing trauma with partially healed fractures on several consecutive ribs. The presence of a relatively large intruder in what is interpreted to be a Thrinaxodon burrow implies that the therapsid tolerated the amphibian’s presence. Among possible explanations for such unlikely cohabitation, Thrinaxodon aestivation is most plausible, an interpretation supported by the numerous Thrinaxodon specimens fossilised in curled-up postures. Recent advances in synchrotron imaging have enabled visualization of the contents of burrow casts, thus providing a novel tool to elucidate not only anatomy but also ecology and biology of ancient tetrapods. PMID:23805181

  20. Classification tree analyses reveal limited potential for early targeted prevention against childhood overweight.

    PubMed

    Beyerlein, Andreas; Kusian, Dennis; Ziegler, Anette-Gabriele; Schaffrath-Rosario, Angelika; von Kries, Rüdiger

    2014-02-01

    Whether specific combinations of risk factors in very early life might allow identification of high-risk target groups for overweight prevention programs was examined. Data of n = 8981 children from the German KiGGS study were analyzed. Using a classification tree approach, predictive risk factor combinations were assessed for overweight in 3-6, 7-10, and 11-17-year-old children. In preschool children, the subgroup with the highest overweight risk were migrant children with at least one obese parent, with a prevalence of 36.6 (95% confidence interval or CI: 22.9, 50.4)%, compared to an overall prevalence of 10.0 (8.9, 11.2)%. The prevalence of overweight increased from 18.3 (16.8, 19.8)% to 57.9 (46.6, 69.3)% in 7-10-year-old children, if at least one parent was obese and the child had been born large-for-gestational-age. In 11-17-year-olds, the overweight risk increased from 20.1 (18.9, 21.3)% to 63.0 (46.4, 79.7)% in the highest risk group. However, high prevalence ratios were found only in small subgroups, containing <10% of all overweight cases in the respective age group. Our results indicate only a limited potential for early targeted preventions against overweight in children and adolescents. Copyright © 2013 The Obesity Society.

  1. Metabotyping Patients’ Journeys Reveals Early Predisposition to Lung Injury after Cardiac Surgery

    PubMed Central

    Maltesen, Raluca Georgiana; Rasmussen, Bodil Steen; Pedersen, Shona; Hanifa, Munsoor Ali; Kucheryavskiy, Sergey; Kristensen, Søren Risom; Wimmer, Reinhard

    2017-01-01

    Cardiovascular disease is the leading cause of death worldwide and patients with severe symptoms undergo cardiac surgery. Even after uncomplicated surgeries, some patients experience postoperative complications such as lung injury. We hypothesized that the procedure elicits metabolic activity that can be related to the disease progression, which is commonly observed two-three days postoperatively. More than 700 blood samples were collected from 50 patients at nine time points pre-, intra-, and postoperatively. Dramatic metabolite shifts were observed during and immediately after the intervention. Prolonged surgical stress was linked to an augmented anaerobic environment. Time series analysis showed shifts in purine-, nicotinic acid-, tyrosine-, hyaluronic acid-, ketone-, fatty acid, and lipid metabolism. A characteristic ‘metabolic biosignature’ was identified correlating with the risk of developing postoperative complications two days before the first clinical signs of lung injury. Hence, this study demonstrates the link between intra- and postoperative time-dependent metabolite changes and later postoperative outcome. In addition, the results indicate that metabotyping patients’ journeys early, during or just after the end of surgery, may have potential impact in hospitals for the early diagnosis of postoperative lung injury, and for the monitoring of therapeutics targeting disease progression. PMID:28074924

  2. Immediate relativity: EEG reveals early engagement of comparison in social information processing.

    PubMed

    Ohmann, Katharina; Stahl, Jutta; Mussweiler, Thomas; Kedia, Gayannée

    2016-11-01

    A wide array of social decisions relies on social comparisons. As such, these decisions require fast access to relative information. Therefore, we expect that signatures of the comparative process should be observable in electrophysiological components at an early stage of information processing. However, to date, little is known about the neural time course of social target comparisons. Therefore, we tested this hypothesis in 2 electroencephalography (EEG) studies using a social distance effect paradigm. The distance effect capitalizes on the fact that stimuli close on a certain dimension take longer to compare than stimuli clearly differing on this dimension. Here, we manipulated the distance of face characteristics regarding their levels of attractiveness (Study 1) and trustworthiness (Study 2), 2 essential social dimensions. In both studies, size comparisons served as a nonsocial control condition. In Study 1, distance related effects were apparent 170 ms (vertex positive potential, VPP) and 200 ms (N2) after stimulus onset for attractiveness comparisons. In Study 2, trustworthiness comparisons took effect already after 100 ms (N1) and likewise carried over to an event-related N2. Remarkably, we observed a similar temporal pattern for social (attractiveness, trustworthiness) and nonsocial (size) dimensions. These results speak in favor of an early encoding of comparative information and emphasize the primary role of comparison in social information processing. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  3. Experience-dependent hemispheric specialization of letters and numbers is revealed in early visual processing.

    PubMed

    Park, Joonkoo; Chiang, Crystal; Brannon, Elizabeth M; Woldorff, Marty G

    2014-10-01

    Recent fMRI research has demonstrated that letters and numbers are preferentially processed in distinct regions and hemispheres in the visual cortex. In particular, the left visual cortex preferentially processes letters compared with numbers, whereas the right visual cortex preferentially processes numbers compared with letters. Because letters and numbers are cultural inventions and are otherwise physically arbitrary, such a double dissociation is strong evidence for experiential effects on neural architecture. Here, we use the high temporal resolution of ERPs to investigate the temporal dynamics of the neural dissociation between letters and numbers. We show that the divergence between ERP traces to letters and numbers emerges very early in processing. Letters evoked greater N1 waves (latencies 140-170 msec) than did numbers over left occipital channels, whereas numbers evoked greater N1s than letters over the right, suggesting letters and numbers are preferentially processed in opposite hemispheres early in visual encoding. Moreover, strings of letters, but not single letters, elicited greater P2 ERP waves (starting around 250 msec) than numbers did over the left hemisphere, suggesting that the visual cortex is tuned to selectively process combinations of letters, but not numbers, further along in the visual processing stream. Additionally, the processing of both of these culturally defined stimulus types differentiated from similar but unfamiliar visual stimulus forms (false fonts) even earlier in the processing stream (the P1 at 100 msec). These findings imply major cortical specialization processes within the visual system driven by experience with reading and mathematics.

  4. Discriminating signal from noise in the fossil record of early vertebrates reveals cryptic evolutionary history

    PubMed Central

    Sansom, Robert S.; Randle, Emma; Donoghue, Philip C. J.

    2015-01-01

    The fossil record of early vertebrates has been influential in elucidating the evolutionary assembly of the gnathostome bodyplan. Understanding of the timing and tempo of vertebrate innovations remains, however, mired in a literal reading of the fossil record. Early jawless vertebrates (ostracoderms) exhibit restriction to shallow-water environments. The distribution of their stratigraphic occurrences therefore reflects not only flux in diversity, but also secular variation in facies representation of the rock record. Using stratigraphic, phylogenetic and palaeoenvironmental data, we assessed the veracity of the fossil records of the jawless relatives of jawed vertebrates (Osteostraci, Galeaspida, Thelodonti, Heterostraci). Non-random models of fossil recovery potential using Palaeozoic sea-level changes were used to calculate confidence intervals of clade origins. These intervals extend the timescale for possible origins into the Upper Ordovician; these estimates ameliorate the long ghost lineages inferred for Osteostraci, Galeaspida and Heterostraci, given their known stratigraphic occurrences and stem–gnathostome phylogeny. Diversity changes through the Silurian and Devonian were found to lie within the expected limits predicted from estimates of fossil record quality indicating that it is geological, rather than biological factors, that are responsible for shifts in diversity. Environmental restriction also appears to belie ostracoderm extinction and demise rather than competition with jawed vertebrates. PMID:25520359

  5. Starch grains reveal early root crop horticulture in the Panamanian tropical forest.

    PubMed

    Piperno, D R; Ranere, A J; Holst, I; Hansell, P

    2000-10-19

    Native American populations are known to have cultivated a large number of plants and domesticated them for their starch-rich underground organs. Suggestions that the likely source of many of these crops, the tropical forest, was an early and influential centre of plant husbandry have long been controversial because the organic remains of roots and tubers are poorly preserved in archaeological sediments from the humid tropics. Here we report the occurrence of starch grains identifiable as manioc (Manihot esculenta Crantz), yams (Dioscorea sp.) and arrowroot (Maranta arundinacea L.) on assemblages of plant milling stones from preceramic horizons at the Aguadulce Shelter, Panama, dated between 7,000 and 5,000 years before present (BP). The artefacts also contain maize starch (Zea mays L.), indicating that early horticultural systems in this region were mixtures of root and seed crops. The data provide the earliest direct evidence for root crop cultivation in the Americas, and support an ancient and independent emergence of plant domestication in the lowland Neotropical forest.

  6. Deaf-Blind Perspectives, 1997-1998.

    ERIC Educational Resources Information Center

    Deaf-Blind Perspectives, 1998

    1998-01-01

    This one-year collection of three serial issues focuses on problem solving skills for children with deaf-blindness, the history and change in the education of children who are deaf-blind since the rubella epidemic of the 1960's, and early identification of infants who are deaf-blind. Specific articles include: (1) "Research to Practice Focus…

  7. Early activation of quorum sensing in Pseudomonas aeruginosa reveals the architecture of a complex regulon.

    PubMed

    Schuster, Martin; Greenberg, E Peter

    2007-08-22

    Quorum-sensing regulation of gene expression in Pseudomonas aeruginosa is complex. Two interconnected acyl-homoserine lactone (acyl-HSL) signal-receptor pairs, 3-oxo-dodecanoyl-HSL-LasR and butanoyl-HSL-RhlR, regulate more than 300 genes. The induction of most of the genes is delayed during growth of P. aeruginosa in complex medium, cannot be advanced by addition of exogenous signal, and requires additional regulatory components. Many of these late genes can be induced by addition of signals early by using specific media conditions. While several factors super-regulate the quorum receptors, others may co-regulate target promoters or may affect expression posttranscriptionally. To better understand the contributions of super-regulation and co-regulation to quorum-sensing gene expression, and to better understand the general structure of the quorum sensing network, we ectopically expressed the two receptors (in the presence of their cognate signals) and another component that affects quorum sensing, the stationary phase sigma factor RpoS, early in growth. We determined the effect on target gene expression by microarray and real-time PCR analysis. Our results show that many target genes (e.g. lasB and hcnABC) are directly responsive to receptor protein levels. Most genes (e.g. lasA, lecA, and phnAB), however, are not significantly affected, although at least some of these genes are directly regulated by quorum sensing. The majority of promoters advanced by RhlR appeared to be regulated directly, which allowed us to build a RhlR consensus sequence. The direct responsiveness of many quorum sensing target genes to receptor protein levels early in growth confirms the role of super-regulation in quorum sensing gene expression. The observation that the induction of most target genes is not affected by signal or receptor protein levels indicates that either target promoters are co-regulated by other transcription factors, or that expression is controlled

  8. The behavior of larval zebrafish reveals stressor-mediated anorexia during early vertebrate development

    PubMed Central

    De Marco, Rodrigo J.; Groneberg, Antonia H.; Yeh, Chen-Min; Treviño, Mario; Ryu, Soojin

    2014-01-01

    The relationship between stress and food consumption has been well documented in adults but less so in developing vertebrates. Here we demonstrate that an encounter with a stressor can suppress food consumption in larval zebrafish. Furthermore, we provide indication that food intake suppression cannot be accounted for by changes in locomotion, oxygen consumption and visual responses, as they remain unaffected after exposure to a potent stressor. We also show that feeding reoccurs when basal levels of cortisol (stress hormone in humans and teleosts) are re-established. The results present evidence that the onset of stress can switch off the drive for feeding very early in vertebrate development, and add a novel endpoint for analyses of metabolic and behavioral disorders in an organism suitable for high-throughput genetics and non-invasive brain imaging. PMID:25368561

  9. Infrasound reveals transition to oscillatory discharge regime during lava fountaining: Implication for early warning

    NASA Astrophysics Data System (ADS)

    Ulivieri, Giacomo; Ripepe, Maurizio; Marchetti, Emanuele

    2013-06-01

    present the analysis of ~4 million infrasonic signals which include 39 episodes of lava fountains recorded at 5.5 km from the active vents. We show that each eruptive episode is characterized by a distinctive trend in the amplitude, waveform, and frequency content of the acoustic signals, reflecting different explosive levels. Lava fountain starts with an ~93 min long violent phase of acoustic transients at ~1.25 Hz repeating every 2-5 s. Infrasound suddenly evolves into a persistent low-frequency quasi-monochromatic pressure oscillation at ~0.4 Hz. We interpret this shift as induced by the transition from the slug (discrete Strombolian) to churn flow (sustained lava fountain) regime that is reflecting an increase in the gas discharge rate. We calculate that infrasonic transition can occur at a gas superficial velocity of ≤76 m/s and it can be used to define infrasonic-based thresholds for an efficient early warning system.

  10. Exceptional preservation reveals gastrointestinal anatomy and evolution in early actinopterygian fishes

    PubMed Central

    Argyriou, Thodoris; Clauss, Marcus; Maxwell, Erin E.; Furrer, Heinz; Sánchez-Villagra, Marcelo R.

    2016-01-01

    Current knowledge about the evolutionary morphology of the vertebrate gastrointestinal tract (GIT) is hindered by the low preservation potential of soft tissues in fossils. Exceptionally preserved cololites of individual †Saurichthys from the Middle Triassic of Switzerland provide unique insights into the evolutionary morphology of the GIT. The GIT of †Saurichthys differed from that of other early actinopterygians, and was convergent to that of some living sharks and rays, in exhibiting up to 30 turns of the spiral valve. Dissections and literature review demonstrate the phylogenetic diversity of GIT features and signs of biological factors that influence its morphology. A phylogenetically informed analysis of a dataset containing 134 taxa suggests that body size and phylogeny are important factors affecting the spiral valve turn counts. The high number of turns in the spiral valve of †Saurichthys and some recent sharks and rays reflect both energetically demanding lifestyles and the evolutionary histories of the groups. PMID:26732746

  11. Ancient igneous intrusions and early expansion of the Moon revealed by GRAIL gravity gradiometry.

    PubMed

    Andrews-Hanna, Jeffrey C; Asmar, Sami W; Head, James W; Kiefer, Walter S; Konopliv, Alexander S; Lemoine, Frank G; Matsuyama, Isamu; Mazarico, Erwan; McGovern, Patrick J; Melosh, H Jay; Neumann, Gregory A; Nimmo, Francis; Phillips, Roger J; Smith, David E; Solomon, Sean C; Taylor, G Jeffrey; Wieczorek, Mark A; Williams, James G; Zuber, Maria T

    2013-02-08

    The earliest history of the Moon is poorly preserved in the surface geologic record due to the high flux of impactors, but aspects of that history may be preserved in subsurface structures. Application of gravity gradiometry to observations by the Gravity Recovery and Interior Laboratory (GRAIL) mission results in the identification of a population of linear gravity anomalies with lengths of hundreds of kilometers. Inversion of the gravity anomalies indicates elongated positive-density anomalies that are interpreted to be ancient vertical tabular intrusions or dikes formed by magmatism in combination with extension of the lithosphere. Crosscutting relationships support a pre-Nectarian to Nectarian age, preceding the end of the heavy bombardment of the Moon. The distribution, orientation, and dimensions of the intrusions indicate a globally isotropic extensional stress state arising from an increase in the Moon's radius by 0.6 to 4.9 kilometers early in lunar history, consistent with predictions of thermal models.

  12. The behavior of larval zebrafish reveals stressor-mediated anorexia during early vertebrate development.

    PubMed

    De Marco, Rodrigo J; Groneberg, Antonia H; Yeh, Chen-Min; Treviño, Mario; Ryu, Soojin

    2014-01-01

    The relationship between stress and food consumption has been well documented in adults but less so in developing vertebrates. Here we demonstrate that an encounter with a stressor can suppress food consumption in larval zebrafish. Furthermore, we provide indication that food intake suppression cannot be accounted for by changes in locomotion, oxygen consumption and visual responses, as they remain unaffected after exposure to a potent stressor. We also show that feeding reoccurs when basal levels of cortisol (stress hormone in humans and teleosts) are re-established. The results present evidence that the onset of stress can switch off the drive for feeding very early in vertebrate development, and add a novel endpoint for analyses of metabolic and behavioral disorders in an organism suitable for high-throughput genetics and non-invasive brain imaging.

  13. RNA-seq Analysis of Clinical-Grade Osteochondral Allografts Reveals Activation of Early Response Genes

    PubMed Central

    Lin, Yang; Lewallen, Eric A.; Camilleri, Emily T.; Bonin, Carolina A.; Jones, Dakota L.; Dudakovic, Amel; Galeano-Garces, Catalina; Wang, Wei; Karperien, Marcel J.; Larson, Annalise N.; Dahm, Diane L.; Stuart, Michael J.; Levy, Bruce A.; Smith, Jay; Ryssman, Daniel B.; Westendorf, Jennifer J.; Im, Hee-Jeong; van Wijnen, Andre J.; Riester, Scott M.; Krych, Aaron J.

    2016-01-01

    Preservation of osteochondral allografts used for transplantation is critical to ensure favorable outcomes for patients after surgical treatment of cartilage defects. To study the biological effects of protocols currently used for cartilage storage, we investigated differences in gene expression between stored allograft cartilage and fresh cartilage from living donors using high throughput molecular screening strategies. We applied next generation RNA sequencing (RNA-seq) and real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) to assess genome-wide differences in mRNA expression between stored allograft cartilage and fresh cartilage tissue from living donors. Gene ontology analysis was used to characterize biological pathways associated with differentially expressed genes. Our studies establish reduced levels of mRNAs encoding cartilage related extracellular matrix (ECM) proteins (i.e., COL1A1, COL2A1, COL10A1, ACAN, DCN, HAPLN1, TNC, and COMP) in stored cartilage. These changes occur concomitantly with increased expression of “early response genes” that encode transcription factors mediating stress/cytoprotective responses (i.e., EGR1, EGR2, EGR3, MYC, FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND). The elevated expression of “early response genes” and reduced levels of ECM-related mRNAs in stored cartilage allografts suggests that tissue viability may be maintained by a cytoprotective program that reduces cell metabolic activity. These findings have potential implications for future studies focused on quality assessment and clinical optimization of osteochondral allografts used for cartilage transplantation. PMID:26909883

  14. Ancient DNA reveals genetic connections between early Di-Qiang and Han Chinese.

    PubMed

    Li, Jiawei; Zeng, Wen; Zhang, Ye; Ko, Albert Min-Shan; Li, Chunxiang; Zhu, Hong; Fu, Qiaomei; Zhou, Hui

    2017-12-04

    Ancient Di-Qiang people once resided in the Ganqing region of China, adjacent to the Central Plain area from where Han Chinese originated. While gene flow between the Di-Qiang and Han Chinese has been proposed, there is no evidence to support this view. Here we analyzed the human remains from an early Di-Qiang site (Mogou site dated ~4000 years old) and compared them to other ancient DNA across China, including an early Han-related site (Hengbei site dated ~3000 years old) to establish the underlying genetic relationship between the Di-Qiang and ancestors of Han Chinese. We found Mogou mtDNA haplogroups were highly diverse, comprising 14 haplogroups: A, B, C, D (D*, D4, D5), F, G, M7, M8, M10, M13, M25, N*, N9a, and Z. In contrast, Mogou males were all Y-DNA haplogroup O3a2/P201; specifically one male was further assigned to O3a2c1a/M117 using targeted unique regions on the non-recombining region of the Y-chromosome. We compared Mogou to 7 other ancient and 38 modern Chinese groups, in a total of 1793 individuals, and found that Mogou shared close genetic distances with Taojiazhai (a more recent Di-Qiang population), Hengbei, and Northern Han. We modeled their interactions using Approximate Bayesian Computation, and support was given to a potential admixture of ~13-18% between the Mogou and Northern Han around 3300-3800 years ago. Mogou harbors the earliest genetically identifiable Di-Qiang, ancestral to the Taojiazhai, and up to ~33% paternal and ~70% of its maternal haplogroups could be found in present-day Northern Han Chinese.

  15. Experience-Dependent Hemispheric Specialization of Letters and Numbers is Revealed in Early Visual Processing

    PubMed Central

    Park, Joonkoo; Chiang, Crystal; Brannon, Elizabeth M.; Woldorff, Marty G.

    2014-01-01

    Recent functional magnetic resonance imaging research has demonstrated that letters and numbers are preferentially processed in distinct regions and hemispheres in the visual cortex. In particular, the left visual cortex preferentially processes letters compared to numbers, while the right visual cortex preferentially processes numbers compared to letters. Because letters and numbers are cultural inventions and are otherwise physically arbitrary, such a double dissociation is strong evidence for experiential effects on neural architecture. Here, we use the high temporal resolution of event-related potentials (ERPs) to investigate the temporal dynamics of the neural dissociation between letters and numbers. We show that the divergence between ERP traces to letters and numbers emerges very early in processing. Letters evoked greater N1 waves (latencies 140–170 ms) than did numbers over left occipital channels, while numbers evoked greater N1s than letters over the right, suggesting letters and numbers are preferentially processed in opposite hemispheres early in visual encoding. Moreover, strings of letters, but not single letters, elicited greater P2 ERP waves, (starting around 250 ms) than numbers did over the left hemisphere, suggesting that the visual cortex is tuned to selectively process combinations of letters, but not numbers, further along in the visual processing stream. Additionally, the processing of both of these culturally defined stimulus types differentiated from similar but unfamiliar visual stimulus forms (false fonts) even earlier in the processing stream (the P1 at 100 ms). These findings imply major cortical specialization processes within the visual system driven by experience with reading and mathematics. PMID:24669789

  16. RNA-seq analysis of clinical-grade osteochondral allografts reveals activation of early response genes.

    PubMed

    Lin, Yang; Lewallen, Eric A; Camilleri, Emily T; Bonin, Carolina A; Jones, Dakota L; Dudakovic, Amel; Galeano-Garces, Catalina; Wang, Wei; Karperien, Marcel J; Larson, Annalise N; Dahm, Diane L; Stuart, Michael J; Levy, Bruce A; Smith, Jay; Ryssman, Daniel B; Westendorf, Jennifer J; Im, Hee-Jeong; van Wijnen, Andre J; Riester, Scott M; Krych, Aaron J

    2016-11-01

    Preservation of osteochondral allografts used for transplantation is critical to ensure favorable outcomes for patients after surgical treatment of cartilage defects. To study the biological effects of protocols currently used for cartilage storage, we investigated differences in gene expression between stored allograft cartilage and fresh cartilage from living donors using high throughput molecular screening strategies. We applied next generation RNA sequencing (RNA-seq) and real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) to assess genome-wide differences in mRNA expression between stored allograft cartilage and fresh cartilage tissue from living donors. Gene ontology analysis was used to characterize biological pathways associated with differentially expressed genes. Our studies establish reduced levels of mRNAs encoding cartilage related extracellular matrix (ECM) proteins (i.e., COL1A1, COL2A1, COL10A1, ACAN, DCN, HAPLN1, TNC, and COMP) in stored cartilage. These changes occur concomitantly with increased expression of "early response genes" that encode transcription factors mediating stress/cytoprotective responses (i.e., EGR1, EGR2, EGR3, MYC, FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND). The elevated expression of "early response genes" and reduced levels of ECM-related mRNAs in stored cartilage allografts suggests that tissue viability may be maintained by a cytoprotective program that reduces cell metabolic activity. These findings have potential implications for future studies focused on quality assessment and clinical optimization of osteochondral allografts used for cartilage transplantation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1950-1959, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  17. Gene expression profiles reveal key genes for early diagnosis and treatment of adamantinomatous craniopharyngioma.

    PubMed

    Yang, Jun; Hou, Ziming; Wang, Changjiang; Wang, Hao; Zhang, Hongbing

    2018-04-23

    Adamantinomatous craniopharyngioma (ACP) is an aggressive brain tumor that occurs predominantly in the pediatric population. Conventional diagnosis method and standard therapy cannot treat ACPs effectively. In this paper, we aimed to identify key genes for ACP early diagnosis and treatment. Datasets GSE94349 and GSE68015 were obtained from Gene Expression Omnibus database. Consensus clustering was applied to discover the gene clusters in the expression data of GSE94349 and functional enrichment analysis was performed on gene set in each cluster. The protein-protein interaction (PPI) network was built by the Search Tool for the Retrieval of Interacting Genes, and hubs were selected. Support vector machine (SVM) model was built based on the signature genes identified from enrichment analysis and PPI network. Dataset GSE94349 was used for training and testing, and GSE68015 was used for validation. Besides, RT-qPCR analysis was performed to analyze the expression of signature genes in ACP samples compared with normal controls. Seven gene clusters were discovered in the differentially expressed genes identified from GSE94349 dataset. Enrichment analysis of each cluster identified 25 pathways that highly associated with ACP. PPI network was built and 46 hubs were determined. Twenty-five pathway-related genes that overlapped with the hubs in PPI network were used as signatures to establish the SVM diagnosis model for ACP. The prediction accuracy of SVM model for training, testing, and validation data were 94, 85, and 74%, respectively. The expression of CDH1, CCL2, ITGA2, COL8A1, COL6A2, and COL6A3 were significantly upregulated in ACP tumor samples, while CAMK2A, RIMS1, NEFL, SYT1, and STX1A were significantly downregulated, which were consistent with the differentially expressed gene analysis. SVM model is a promising classification tool for screening and early diagnosis of ACP. The ACP-related pathways and signature genes will advance our knowledge of ACP pathogenesis

  18. Color discrimination testing reveals early printshop solvent neurotoxicity better than a neuropsychological test battery.

    PubMed

    Braun, C M; Daigneault, S; Gilbert, B

    1989-01-01

    Twenty standardized neuropsychological tests were compared to the Lanthony D-15 desaturated panel test of chromotopsia to determine which measures would most effectively discriminate solvent-exposed print workers from controls. All the workers of the printing services of Université du Québec a Montréal (N = 29) were assessed excepted one who refused to participate. Twenty-nine workers (employed on a full time basis) matched for occupation, age, sex, education, vocabulary, and written arithmetic (p >.13) with the print workers served as controls. Air samples revealed exposure to ethanol, perchloroethylene, methyl chloride, xylene, toluene, and stoddard solvent in the print shop. None of the 20 neuropsychological measures yielded a statistically significant decrement in the print workers. On the other hand, the Lanthony D-15 test revealed a significant group difference (p <.01) and a highly significant interaction between job category within the print shop and dyschromatopsia (p <.001) - the graphists, photocopiers, and printers/binders manifesting increasing severity of impairment as a function of increasing magnitude, and/or type, of dose. The results were interpreted to mean that in a cohort of printers with low seniority (10.42 years) such as this one, neuro-opthalmotoxic effects can be observed earlier than putative neuropsychotoxic effects with the tools at hand.

  19. Rotigotine Effects on Early Morning Motor Function and Sleep in Parkinson's Disease: A Double-Blind, Randomized, pLacebo-Controlled Study (RECOVER)

    PubMed Central

    Trenkwalder, Claudia; Kies, Bryan; Rudzinska, Monika; Fine, Jennifer; Nikl, Janos; Honczarenko, Krystyna; Dioszeghy, Peter; Hill, Dennis; Anderson, Tim; Myllyla, Vilho; Kassubek, Jan; Steiger, Malcolm; Zucconi, Marco; Tolosa, Eduardo; Poewe, Werner; Surmann, Erwin; Whitesides, John; Boroojerdi, Babak; Chaudhuri, Kallol Ray

    2011-01-01

    In a multinational, double-blind, placebo-controlled trial (NCT00474058), 287 subjects with Parkinson's disease (PD) and unsatisfactory early-morning motor symptom control were randomized 2:1 to receive rotigotine (2–16 mg/24 hr [n = 190]) or placebo (n = 97). Treatment was titrated to optimal dose over 1–8 weeks with subsequent dose maintenance for 4 weeks. Early-morning motor function and nocturnal sleep disturbance were assessed as coprimary efficacy endpoints using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Examination) measured in the early morning prior to any medication intake and the modified Parkinson's Disease Sleep Scale (PDSS-2) (mean change from baseline to end of maintenance [EOM], last observation carried forward). At EOM, mean UPDRS Part III score had decreased by −7.0 points with rotigotine (from a baseline of 29.6 [standard deviation (SD) 12.3] and by −3.9 points with placebo (baseline 32.0 [13.3]). Mean PDSS-2 total score had decreased by −5.9 points with rotigotine (from a baseline of 19.3 [SD 9.3]) and by −1.9 points with placebo (baseline 20.5 [10.4]). This represented a significantly greater improvement with rotigotine compared with placebo on both the UPDRS Part III (treatment difference: −3.55 [95% confidence interval (CI) −5.37, −1.73]; P = 0.0002) and PDSS-2 (treatment difference: −4.26 [95% CI −6.08, −2.45]; P < 0.0001). The most frequently reported adverse events were nausea (placebo, 9%; rotigotine, 21%), application site reactions (placebo, 4%; rotigotine, 15%), and dizziness (placebo, 6%; rotigotine 10%). Twenty-four-hour transdermal delivery of rotigotine to PD patients with early-morning motor dysfunction resulted in significant benefits in control of both motor function and nocturnal sleep disturbances. © 2010 Movement Disorder Society PMID:21322021

  20. Targeted Metabolomics Reveals Early Dominant Optic Atrophy Signature in Optic Nerves of Opa1delTTAG/+ Mice.

    PubMed

    Chao de la Barca, Juan Manuel; Simard, Gilles; Sarzi, Emmanuelle; Chaumette, Tanguy; Rousseau, Guillaume; Chupin, Stéphanie; Gadras, Cédric; Tessier, Lydie; Ferré, Marc; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Gueguen, Naïg; Leruez, Stéphanie; Verny, Christophe; Miléa, Dan; Bonneau, Dominique; Amati-Bonneau, Patrizia; Procaccio, Vincent; Hamel, Christian; Lenaers, Guy; Reynier, Pascal; Prunier-Mirebeau, Delphine

    2017-02-01

    Dominant optic atrophy (MIM No. 165500) is a blinding condition related to mutations in OPA1, a gene encoding a large GTPase involved in mitochondrial inner membrane dynamics. Although several mouse models mimicking the disease have been developed, the pathophysiological mechanisms responsible for retinal ganglion cell degeneration remain poorly understood. Using a targeted metabolomic approach, we measured the concentrations of 188 metabolites in nine tissues, that is, brain, three types of skeletal muscle, heart, liver, retina, optic nerve, and plasma in symptomatic 11-month-old Opa1delTTAG/+ mice. Significant metabolic signatures were found only in the optic nerve and plasma of female mice. The optic nerve signature was characterized by altered concentrations of phospholipids, amino acids, acylcarnitines, and carnosine, whereas the plasma signature showed decreased concentrations of amino acids and sarcosine associated with increased concentrations of several phospholipids. In contrast, the investigation of 3-month-old presymptomatic Opa1delTTAG/+ mice showed no specific plasma signature but revealed a significant optic nerve signature in both sexes, although with a sex effect. The Opa1delTTAG/+ versus wild-type optic nerve signature was characterized by the decreased concentrations of 10 sphingomyelins and 10 lysophosphatidylcholines, suggestive of myelin sheath alteration, and by alteration in the concentrations of metabolites involved in neuroprotection, such as dimethylarginine, carnitine, spermine, spermidine, carnosine, and glutamate, suggesting a concomitant axonal metabolic dysfunction. Our comprehensive metabolomic investigations revealed in symptomatic as well as in presymptomatic Opa1delTTAG/+ mice, a specific sensitiveness of the optic nerve to Opa1 insufficiency, opening new routes for protective therapeutic strategies.

  1. Single-cell RNA sequencing reveals developmental heterogeneity among early lymphoid progenitors.

    PubMed

    Alberti-Servera, Llucia; von Muenchow, Lilly; Tsapogas, Panagiotis; Capoferri, Giuseppina; Eschbach, Katja; Beisel, Christian; Ceredig, Rhodri; Ivanek, Robert; Rolink, Antonius

    2017-12-15

    Single-cell RNA sequencing is a powerful technology for assessing heterogeneity within defined cell populations. Here, we describe the heterogeneity of a B220 + CD117 int CD19 - NK1.1 - uncommitted hematopoietic progenitor having combined lymphoid and myeloid potential. Phenotypic and functional assays revealed four subpopulations within the progenitor with distinct lineage developmental potentials. Among them, the Ly6D + SiglecH - CD11c - fraction was lymphoid-restricted exhibiting strong B-cell potential, whereas the Ly6D - SiglecH - CD11c - fraction showed mixed lympho-myeloid potential. Single-cell RNA sequencing of these subsets revealed that the latter population comprised a mixture of cells with distinct lymphoid and myeloid transcriptional signatures and identified a subgroup as the potential precursor of Ly6D + SiglecH - CD11c - Subsequent functional assays confirmed that B220 + CD117 int CD19 - NK1.1 - single cells are, with rare exceptions, not bipotent for lymphoid and myeloid lineages. A B-cell priming gradient was observed within the Ly6D + SiglecH - CD11c - subset and we propose a herein newly identified subgroup as the direct precursor of the first B-cell committed stage. Therefore, the apparent multipotency of B220 + CD117 int CD19 - NK1.1 - progenitors results from underlying heterogeneity at the single-cell level and highlights the validity of single-cell transcriptomics for resolving cellular heterogeneity and developmental relationships among hematopoietic progenitors. © 2017 The Authors.

  2. Multiplex lexical networks reveal patterns in early word acquisition in children

    NASA Astrophysics Data System (ADS)

    Stella, Massimo; Beckage, Nicole M.; Brede, Markus

    2017-04-01

    Network models of language have provided a way of linking cognitive processes to language structure. However, current approaches focus only on one linguistic relationship at a time, missing the complex multi-relational nature of language. In this work, we overcome this limitation by modelling the mental lexicon of English-speaking toddlers as a multiplex lexical network, i.e. a multi-layered network where N = 529 words/nodes are connected according to four relationship: (i) free association, (ii) feature sharing, (iii) co-occurrence, and (iv) phonological similarity. We investigate the topology of the resulting multiplex and then proceed to evaluate single layers and the full multiplex structure on their ability to predict empirically observed age of acquisition data of English speaking toddlers. We find that the multiplex topology is an important proxy of the cognitive processes of acquisition, capable of capturing emergent lexicon structure. In fact, we show that the multiplex structure is fundamentally more powerful than individual layers in predicting the ordering with which words are acquired. Furthermore, multiplex analysis allows for a quantification of distinct phases of lexical acquisition in early learners: while initially all the multiplex layers contribute to word learning, after about month 23 free associations take the lead in driving word acquisition.

  3. Early Miocene amber inclusions from Mexico reveal antiquity of mangrove-associated copepods

    PubMed Central

    Huys, Rony; Suárez-Morales, Eduardo; Serrano-Sánchez, María de Lourdes; Centeno-García, Elena; Vega, Francisco J.

    2016-01-01

    Copepods are aquatic microcrustaceans and represent the most abundant metazoans on Earth, outnumbering insects and nematode worms. Their position of numerical world predominance can be attributed to three principal radiation events, i.e. their major habitat shift into the marine plankton, the colonization of freshwater and semiterrestrial environments, and the evolution of parasitism. Their variety of life strategies has generated an incredible morphological plasticity and disparity in body form and shape that are arguably unrivalled among the Crustacea. Although their chitinous exoskeleton is largely resistant to chemical degradation copepods are exceedingly scarce in the geological record with limited body fossil evidence being available for only three of the eight currently recognized orders. The preservation of aquatic arthropods in amber is unusual but offers a unique insight into ancient subtropical and tropical ecosystems. Here we report the first discovery of amber-preserved harpacticoid copepods, represented by ten putative species belonging to five families, based on Early Miocene (22.8 million years ago) samples from Chiapas, southeast Mexico. Their close resemblance to Recent mangrove-associated copepods highlights the antiquity of the specialized harpacticoid fauna living in this habitat. With the taxa reported herein, the Mexican amber holds the greatest diversity of fossil copepods worldwide. PMID:27731321

  4. Early Miocene amber inclusions from Mexico reveal antiquity of mangrove-associated copepods.

    PubMed

    Huys, Rony; Suárez-Morales, Eduardo; Serrano-Sánchez, María de Lourdes; Centeno-García, Elena; Vega, Francisco J

    2016-10-12

    Copepods are aquatic microcrustaceans and represent the most abundant metazoans on Earth, outnumbering insects and nematode worms. Their position of numerical world predominance can be attributed to three principal radiation events, i.e. their major habitat shift into the marine plankton, the colonization of freshwater and semiterrestrial environments, and the evolution of parasitism. Their variety of life strategies has generated an incredible morphological plasticity and disparity in body form and shape that are arguably unrivalled among the Crustacea. Although their chitinous exoskeleton is largely resistant to chemical degradation copepods are exceedingly scarce in the geological record with limited body fossil evidence being available for only three of the eight currently recognized orders. The preservation of aquatic arthropods in amber is unusual but offers a unique insight into ancient subtropical and tropical ecosystems. Here we report the first discovery of amber-preserved harpacticoid copepods, represented by ten putative species belonging to five families, based on Early Miocene (22.8 million years ago) samples from Chiapas, southeast Mexico. Their close resemblance to Recent mangrove-associated copepods highlights the antiquity of the specialized harpacticoid fauna living in this habitat. With the taxa reported herein, the Mexican amber holds the greatest diversity of fossil copepods worldwide.

  5. Adaptive genomic evolution of opsins reveals that early mammals flourished in nocturnal environments.

    PubMed

    Borges, Rui; Johnson, Warren E; O'Brien, Stephen J; Gomes, Cidália; Heesy, Christopher P; Antunes, Agostinho

    2018-02-05

    Based on evolutionary patterns of the vertebrate eye, Walls (1942) hypothesized that early placental mammals evolved primarily in nocturnal habitats. However, not only Eutheria, but all mammals show photic characteristics (i.e. dichromatic vision, rod-dominated retina) suggestive of a scotopic eye design. Here, we used integrative comparative genomic and phylogenetic methodologies employing the photoreceptive opsin gene family in 154 mammals to test the likelihood of a nocturnal period in the emergence of all mammals. We showed that mammals possess genomic patterns concordant with a nocturnal ancestry. The loss of the RH2, VA, PARA, PARIE and OPN4x opsins in all mammals led us to advance a probable and most-parsimonious hypothesis of a global nocturnal bottleneck that explains the loss of these genes in the emerging lineage (> > 215.5 million years ago). In addition, ancestral character reconstruction analyses provided strong evidence that ancestral mammals possessed a nocturnal lifestyle, ultra-violet-sensitive vision, low visual acuity and low orbit convergence (i.e. panoramic vision). Overall, this study provides insight into the evolutionary history of the mammalian eye while discussing important ecological aspects of the photic paleo-environments ancestral mammals have occupied.

  6. Gene expression profiling at early organogenesis reveals both common and diverse mechanisms in foregut patterning

    PubMed Central

    Fagman, Henrik; Amendola, Elena; Parrillo, Luca; Zoppoli, Pietro; Marotta, Pina; Scarfò, Marzia; De Luca, Pasquale; de Carvalho, Denise Pires; Ceccarelli, Michele; De Felice, Mario; Di Lauro, Roberto

    2011-01-01

    The thyroid and lungs originate as neighboring bud shaped outgrowths from the midline of the embryonic foregut. When and how organ specific programs regulate development into structures of distinct shapes, positions and functions is incompletely understood. To characterize, at least in part, the genetic basis of these events, we have employed laser capture microdissection and microarray analysis to define gene expression in the mouse thyroid and lung primordia at E10.5. By comparing the transcriptome of each bud to that of the whole embryo as well as to each other, we broadly describe the genes that are preferentially expressed in each developing organ as well as those with an enriched expression common to both. The results thus obtained provide a valuable resource for further analysis of genes previously unrecognized to participate in thyroid and lung morphogenesis and to discover organ specific as well as common developmental mechanisms. As an initial step in this direction we describe a regulatory pathway involving the anti-apoptotic gene Bcl2 that controls cell survival in early thyroid development. PMID:21924257

  7. Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology.

    PubMed

    Radde, Rebecca; Bolmont, Tristan; Kaeser, Stephan A; Coomaraswamy, Janaky; Lindau, Dennis; Stoltze, Lars; Calhoun, Michael E; Jäggi, Fabienne; Wolburg, Hartwig; Gengler, Simon; Haass, Christian; Ghetti, Bernardino; Czech, Christian; Hölscher, Christian; Mathews, Paul M; Jucker, Mathias

    2006-09-01

    We have generated a novel transgenic mouse model on a C57BL/6J genetic background that coexpresses KM670/671NL mutated amyloid precursor protein and L166P mutated presenilin 1 under the control of a neuron-specific Thy1 promoter element (APPPS1 mice). Cerebral amyloidosis starts at 6-8 weeks and the ratio of human amyloid (A)beta42 to Abeta40 is 1.5 and 5 in pre-depositing and amyloid-depositing mice, respectively. Consistent with this ratio, extensive congophilic parenchymal amyloid but minimal amyloid angiopathy is observed. Amyloid-associated pathologies include dystrophic synaptic boutons, hyperphosphorylated tau-positive neuritic structures and robust gliosis, with neocortical microglia number increasing threefold from 1 to 8 months of age. Global neocortical neuron loss is not apparent up to 8 months of age, but local neuron loss in the dentate gyrus is observed. Because of the early onset of amyloid lesions, the defined genetic background of the model and the facile breeding characteristics, APPPS1 mice are well suited for studying therapeutic strategies and the pathomechanism of amyloidosis by cross-breeding to other genetically engineered mouse models.

  8. Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology

    PubMed Central

    Radde, Rebecca; Bolmont, Tristan; Kaeser, Stephan A; Coomaraswamy, Janaky; Lindau, Dennis; Stoltze, Lars; Calhoun, Michael E; Jäggi, Fabienne; Wolburg, Hartwig; Gengler, Simon; Haass, Christian; Ghetti, Bernardino; Czech, Christian; Hölscher, Christian; Mathews, Paul M; Jucker, Mathias

    2006-01-01

    We have generated a novel transgenic mouse model on a C57BL/6J genetic background that coexpresses KM670/671NL mutated amyloid precursor protein and L166P mutated presenilin 1 under the control of a neuron-specific Thy1 promoter element (APPPS1 mice). Cerebral amyloidosis starts at 6–8 weeks and the ratio of human amyloid (A)β42 to Aβ40 is 1.5 and 5 in pre-depositing and amyloid-depositing mice, respectively. Consistent with this ratio, extensive congophilic parenchymal amyloid but minimal amyloid angiopathy is observed. Amyloid-associated pathologies include dystrophic synaptic boutons, hyperphosphorylated tau-positive neuritic structures and robust gliosis, with neocortical microglia number increasing threefold from 1 to 8 months of age. Global neocortical neuron loss is not apparent up to 8 months of age, but local neuron loss in the dentate gyrus is observed. Because of the early onset of amyloid lesions, the defined genetic background of the model and the facile breeding characteristics, APPPS1 mice are well suited for studying therapeutic strategies and the pathomechanism of amyloidosis by cross-breeding to other genetically engineered mouse models. PMID:16906128

  9. Dusty starburst galaxies in the early Universe as revealed by gravitational lensing.

    PubMed

    Vieira, J D; Marrone, D P; Chapman, S C; De Breuck, C; Hezaveh, Y D; Weiβ, A; Aguirre, J E; Aird, K A; Aravena, M; Ashby, M L N; Bayliss, M; Benson, B A; Biggs, A D; Bleem, L E; Bock, J J; Bothwell, M; Bradford, C M; Brodwin, M; Carlstrom, J E; Chang, C L; Crawford, T M; Crites, A T; de Haan, T; Dobbs, M A; Fomalont, E B; Fassnacht, C D; George, E M; Gladders, M D; Gonzalez, A H; Greve, T R; Gullberg, B; Halverson, N W; High, F W; Holder, G P; Holzapfel, W L; Hoover, S; Hrubes, J D; Hunter, T R; Keisler, R; Lee, A T; Leitch, E M; Lueker, M; Luong-Van, D; Malkan, M; McIntyre, V; McMahon, J J; Mehl, J; Menten, K M; Meyer, S S; Mocanu, L M; Murphy, E J; Natoli, T; Padin, S; Plagge, T; Reichardt, C L; Rest, A; Ruel, J; Ruhl, J E; Sharon, K; Schaffer, K K; Shaw, L; Shirokoff, E; Spilker, J S; Stalder, B; Staniszewski, Z; Stark, A A; Story, K; Vanderlinde, K; Welikala, N; Williamson, R

    2013-03-21

    In the past decade, our understanding of galaxy evolution has been revolutionized by the discovery that luminous, dusty starburst galaxies were 1,000 times more abundant in the early Universe than at present. It has, however, been difficult to measure the complete redshift distribution of these objects, especially at the highest redshifts (z > 4). Here we report a redshift survey at a wavelength of three millimetres, targeting carbon monoxide line emission from the star-forming molecular gas in the direction of extraordinarily bright millimetre-wave-selected sources. High-resolution imaging demonstrates that these sources are strongly gravitationally lensed by foreground galaxies. We detect spectral lines in 23 out of 26 sources and multiple lines in 12 of those 23 sources, from which we obtain robust, unambiguous redshifts. At least 10 of the sources are found to lie at z > 4, indicating that the fraction of dusty starburst galaxies at high redshifts is greater than previously thought. Models of lens geometries in the sample indicate that the background objects are ultra-luminous infrared galaxies, powered by extreme bursts of star formation.

  10. EARLY ONSET OF CRANIOSYNOSTOSIS IN AN APERT MOUSE MODEL REVEALS CRITICAL FEATURES OF THIS PATHOLOGY

    PubMed Central

    Holmes, Greg; Rothschild, Gerson; Roy, Upal Basu; Deng, Chu-Xia; Mansukhani, Alka; Basilico, Claudio

    2009-01-01

    Activating mutations of FGFRs1–3 cause craniosynostosis (CS), the premature fusion of cranial bones, in man and mouse. The mechanisms by which such mutations lead to CS have been variously ascribed to increased osteoblast proliferation, differentiation, and apoptosis, but it is not always clear how these disturbances relate to the process of suture fusion. We have reassessed coronal suture fusion in an Apert Fgfr2 (S252W) mouse model. We find that the critical event of CS is the early loss of basal sutural mesenchyme as the osteogenic fronts, expressing activated Fgfr2, unite to form a contiguous skeletogenic membrane. A mild increase in osteoprogenitor proliferation precedes but does not accompany this event, and apoptosis is insignificant. On the other hand, the more apical coronal suture initially forms appropriately but then undergoes fusion, albeit at a slower rate, accompanied by a significant decrease in osteoprogenitor proliferation, and increased osteoblast maturation. Apoptosis now accompanies fusion, but is restricted to bone fronts in contact with one another. We correlated these in vivo observations with the intrinsic effects of the activated Fgfr2 S252W mutation in primary osteoblasts in culture, which show an increased capacity for both proliferation and differentiation. Our studies suggest that the major determinant of Fgfr2-induced craniosynostosis is the failure to respond to signals that would halt the recruitment or the advancement of osteoprogenitor cells at the sites where sutures should normally form. PMID:19389359

  11. Charcoal reflectance reveals early holocene boreal deciduous forests burned at high intensities.

    PubMed

    Hudspith, Victoria A; Belcher, Claire M; Kelly, Ryan; Hu, Feng Sheng

    2015-01-01

    Wildfire size, frequency, and severity are increasing in the Alaskan boreal forest in response to climate warming. One of the potential impacts of this changing fire regime is the alteration of successional trajectories, from black spruce to mixed stands dominated by aspen, a vegetation composition not experienced since the early Holocene. Such changes in vegetation composition may consequently alter the intensity of fires, influencing fire feedbacks to the ecosystem. Paleorecords document past wildfire-vegetation dynamics and as such, are imperative for our understanding of how these ecosystems will respond to future climate warming. For the first time, we have used reflectance measurements of macroscopic charcoal particles (>180μm) from an Alaskan lake-sediment record to estimate ancient charring temperatures (termed pyrolysis intensity). We demonstrate that pyrolysis intensity increased markedly from an interval of birch tundra 11 ky ago (mean 1.52%Ro; 485°C), to the expansion of trees on the landscape ~10.5 ky ago, remaining high to the present (mean 3.54%Ro; 640°C) irrespective of stand composition. Despite differing flammabilities and adaptations to fire, the highest pyrolysis intensities derive from two intervals with distinct vegetation compositions. 1) the expansion of mixed aspen and spruce woodland at 10 cal. kyr BP, and 2) the establishment of black spruce, and the modern boreal forest at 4 cal. kyr BP. Based on our analysis, we infer that predicted expansion of deciduous trees into the boreal forest in the future could lead to high intensity, but low severity fires, potentially moderating future climate-fire feedbacks.

  12. Charcoal Reflectance Reveals Early Holocene Boreal Deciduous Forests Burned at High Intensities

    PubMed Central

    Hudspith, Victoria A.; Belcher, Claire M.; Kelly, Ryan; Hu, Feng Sheng

    2015-01-01

    Wildfire size, frequency, and severity are increasing in the Alaskan boreal forest in response to climate warming. One of the potential impacts of this changing fire regime is the alteration of successional trajectories, from black spruce to mixed stands dominated by aspen, a vegetation composition not experienced since the early Holocene. Such changes in vegetation composition may consequently alter the intensity of fires, influencing fire feedbacks to the ecosystem. Paleorecords document past wildfire-vegetation dynamics and as such, are imperative for our understanding of how these ecosystems will respond to future climate warming. For the first time, we have used reflectance measurements of macroscopic charcoal particles (>180μm) from an Alaskan lake-sediment record to estimate ancient charring temperatures (termed pyrolysis intensity). We demonstrate that pyrolysis intensity increased markedly from an interval of birch tundra 11 ky ago (mean 1.52%Ro; 485°C), to the expansion of trees on the landscape ∼10.5 ky ago, remaining high to the present (mean 3.54%Ro; 640°C) irrespective of stand composition. Despite differing flammabilities and adaptations to fire, the highest pyrolysis intensities derive from two intervals with distinct vegetation compositions. 1) the expansion of mixed aspen and spruce woodland at 10 cal. kyr BP, and 2) the establishment of black spruce, and the modern boreal forest at 4 cal. kyr BP. Based on our analysis, we infer that predicted expansion of deciduous trees into the boreal forest in the future could lead to high intensity, but low severity fires, potentially moderating future climate-fire feedbacks. PMID:25853712

  13. Comparative Genomics of Early-Diverging Brucella Strains Reveals a Novel Lipopolysaccharide Biosynthesis Pathway

    PubMed Central

    Wattam, Alice R.; Inzana, Thomas J.; Williams, Kelly P.; Mane, Shrinivasrao P.; Shukla, Maulik; Almeida, Nalvo F.; Dickerman, Allan W.; Mason, Steven; Moriyón, Ignacio; O’Callaghan, David; Whatmore, Adrian M.; Sobral, Bruno W.; Tiller, Rebekah V.; Hoffmaster, Alex R.; Frace, Michael A.; De Castro, Cristina; Molinaro, Antonio; Boyle, Stephen M.; De, Barun K.; Setubal, João C.

    2012-01-01

    ABSTRACT Brucella species are Gram-negative bacteria that infect mammals. Recently, two unusual strains (Brucella inopinata BO1T and B. inopinata-like BO2) have been isolated from human patients, and their similarity to some atypical brucellae isolated from Australian native rodent species was noted. Here we present a phylogenomic analysis of the draft genome sequences of BO1T and BO2 and of the Australian rodent strains 83-13 and NF2653 that shows that they form two groups well separated from the other sequenced Brucella spp. Several important differences were noted. Both BO1T and BO2 did not agglutinate significantly when live or inactivated cells were exposed to monospecific A and M antisera against O-side chain sugars composed of N-formyl-perosamine. While BO1T maintained the genes required to synthesize a typical Brucella O-antigen, BO2 lacked many of these genes but still produced a smooth LPS (lipopolysaccharide). Most missing genes were found in the wbk region involved in O-antigen synthesis in classic smooth Brucella spp. In their place, BO2 carries four genes that other bacteria use for making a rhamnose-based O-antigen. Electrophoretic, immunoblot, and chemical analyses showed that BO2 carries an antigenically different O-antigen made of repeating hexose-rich oligosaccharide units that made the LPS water-soluble, which contrasts with the homopolymeric O-antigen of other smooth brucellae that have a phenol-soluble LPS. The results demonstrate the existence of a group of early-diverging brucellae with traits that depart significantly from those of the Brucella species described thus far. PMID:22930339

  14. Longitudinal urinary metabolomic profiling reveals metabolites for asthma development in early childhood.

    PubMed

    Chiu, Chih-Yung; Lin, Gigin; Cheng, Mei-Ling; Chiang, Meng-Han; Tsai, Ming-Han; Su, Kuan-Wen; Hua, Man-Chin; Liao, Sui-Ling; Lai, Shen-Hao; Yao, Tsung-Chieh; Yeh, Kuo-Wei; Huang, Jing-Long

    2018-04-21

    Several metabolites and altered metabolic pathways have been reported to be associated with asthma. However, longitudinal analysis of the dynamics of metabolites contributing to the development of asthma has not yet been fully clarified. We sought to identify the metabolic mechanisms underlying asthma development in early childhood. Thirty children with asthma and paired healthy controls from a prospective birth cohort were enrolled. Time-series analysis of urinary metabolites collected at ages 1, 2, 3, and 4 years were assessed using 1 H-nuclear magnetic resonance (NMR) spectroscopy coupled with partial least-squares discriminant analysis (PLS-DA). Metabolites identified were studied in relation to changes over time in a linear mixed model for repeated measures. A total of 172 urine samples collected from the enrolled children were analyzed. Urinary metabolomics identified four metabolites significantly associated with childhood asthma development, with longitudinal analysis. Among them, dimethylamine, a metabolite produced by intestinal bacteria, appeared to shift from higher to lower level during asthma development. A persistent lower level of 1-methylnicotinamide and allantoin was found in children with asthma, with a peak difference at age 3 years (P = 0.032 and P = 0.021 respectively). Furthermore, a significant inverse correlation was found between allantoin and house dust mite sensitization (Spearman's r = -0.297 P = 0.035). Longitudinal urinary metabolomic profiling provides a link of microbe-environment interactions in the development of childhood asthma. 1-Methylnicotinamide and allantoin may participate in allergic reactions in response to allergen exposure, potentially serving as specific biomarkers for asthma. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Genome-wide allelotyping of a new in vitro model system reveals early events in breast cancer progression.

    PubMed

    Li, Zheng; Meng, Zhen Hang; Sayeed, Aejaz; Shalaby, Refaat; Ljung, Britt-Marie; Dairkee, Shanaz H

    2002-10-15

    Toward the goal of identifying early genetic losses, which mediate the release of human breast epithelium from replicative suppression leading to cellular immortalization, we have used a newly developed in vitro model system. This system consists of epithelial cultures derived from noncancerous breast tissue, treated with the chemical carcinogen N-ethyl-N-nitrosourea, and continuously passaged to yield cell populations culminating in the immortal phenotype. Genome-wide allelotyping of early passage N-ethyl-N-nitrosourea-exposed cell populations revealed aberrations at >10% (18 of 169) loci examined. Allelic losses encompassing chromosomes 6q24-6q27, implicating immortalization-associated candidate genes, hZAC and SEN6, occurred in two independently derived cell lines before the Hayflick limit. Additional LOH sites were present in one cell line at 3p11-3p26, 11p15, and 20p12-13. Allelic losses reported in this cell line preceded detectable levels of telomerase activity and the occurrence of p53-related aberrations. Information gained from the search for early immortalization-associated genetic deletions in cultured cells was applied in a novel approach toward the analysis of morphologically normal terminal ductal lobular units microdissected from 20 cases of ductal carcinoma in situ. Notably, clonal allelic losses at chromosome 3p24 and 6q24 were an early occurrence in adjoining terminal ductal lobular units of a proportion of primary tumors, which displayed loss of heterozygosity (3 of 11 and 3 of 6, respectively). The biological insights provided by the new model system reported here strongly suggest that early allelic losses delineated in immortalized cultures and validated in vivo could serve as surrogate endpoints to assist in the identification and intervention of high-risk benign breast tissue, which sustains the potential for continuous proliferation.

  16. Lethality in PARP-1/Ku80 double mutant mice reveals physiologicalsynergy during early embryogenesis

    SciTech Connect

    Henrie, Melinda S.; Kurimasa, Akihiro; Burma, Sandeep

    2002-09-24

    Ku is an abundant heterodimeric nuclear protein, consisting of 70-kDa and 86-kDa tightly associated subunits that comprise the DNA binding component of DNA-dependent protein kinase. Poly(ADP)ribose polymerase-1 (PARP-1) is a 113-kDa protein that catalyzes the synthesis of poly(ADP-ribose) on target proteins. Both Ku and PARP-1 recognize and bind to DNA ends. Ku functions in the non-homologous end joining (NHEJ) repair pathway whereas PARP-1 functions in the single strand break repair and base excision repair (BER) pathways. Recent studies have revealed that PARP-1 and Ku80 interact in vitro. To determine whether the association of PARP-1 and Ku80 has any physiological significancemore » or synergistic function in vivo, mice lacking both PARP-1 and Ku80 were generated. The resulting offspring died during embryonic development displaying abnormalities around the gastrulation stage. In addition, PARP-1-/-Ku80-/- cultured blastocysts had an increased level of apoptosis. These data suggest that the functions of both Ku80 and PARP-1 are essential for normal embryogenesis and that a loss of genomic integrity leading to cell death through apoptosis is likely the cause of the embryonic lethality observed in these mice.« less

  17. Liquefaction along Late Pleistocene to early Holocene Faults as Revealed by Lidar in Northwest Tasmania, Australia

    NASA Astrophysics Data System (ADS)

    Webb, J.; Gardner, T.

    2016-12-01

    In northwest Tasmania well-preserved mid-Holocene beach ridges with maximum radiocarbon ages of 5.25 ka occur along the coast; inland are a parallel set of lower relief beach ridges of probable MIS 5e age. The latter are cut by northeast-striking faults clearly visible on LIDAR images, with a maximum vertical displacement (evident as difference in topographic elevation) of 3 m. Also distinct on the LIDAR images are large sand boils along the fault lines; they are up to 5 m in diameter and 2-3 m high and mostly occur on the hanging wall close to the fault traces. Without LIDAR it would have been almost impossible to distinguish either the fault scarps or the sand boils. Excavations through the sand boils show that they are massive, with no internal structure, suggesting that they formed in a single event. They are composed of well-sorted, very fine white sand, identical to the sand in the underlying beach ridges. The sand boils overlie a peaty paleosol; this formed in the tea-tree swamp that formerly covered the area, and has been offset along the faults. Radiocarbon dating of the buried organic-rich paleosol gave ages of 14.8-7.2 ka, suggesting that the faulting is latest Pleistocene to early Holocene in age; it occurred prior to deposition of the mid-Holocene beach ridges, which are not offset. The beach ridge sediments are up to 7 m thick and contain an iron-cemented hard pan 1-3 m below the surface. The water table is very shallow and close to the ground surface, so the sands of the beach ridges are mostly saturated. During faulting these sands experienced extensive liquefaction. The resulting sand boils rose to a substantial height of 2-3 m, probably possibly reflecting the elevation of the potentiometric surface within the confined part of the beach ridge sediments below the iron-cemented hard pan. Motion on the faults was predominantly dip slip (shown by an absence of horizontal offset) and probably reverse, which is consistent with the present-day northwest

  18. A zebrafish larval model reveals early tissue-specific innate immune responses to Mucor circinelloides.

    PubMed

    Voelz, Kerstin; Gratacap, Remi L; Wheeler, Robert T

    2015-11-01

    Mucormycosis is an emerging fungal infection that is clinically difficult to manage, with increasing incidence and extremely high mortality rates. Individuals with diabetes, suppressed immunity or traumatic injury are at increased risk of developing disease. These individuals often present with defects in phagocytic effector cell function. Research using mammalian models and phagocytic effector cell lines has attempted to decipher the importance of the innate immune system in host defence against mucormycosis. However, these model systems have not been satisfactory for direct analysis of the interaction between innate immune effector cells and infectious sporangiospores in vivo. Here, we report the first real-time in vivo analysis of the early innate immune response to mucormycete infection using a whole-animal zebrafish larval model system. We identified differential host susceptibility, dependent on the site of infection (hindbrain ventricle and swim bladder), as well as differential functions of the two major phagocyte effector cell types in response to viable and non-viable spores. Larval susceptibility to mucormycete spore infection was increased upon immunosuppressant treatment. We showed for the first time that macrophages and neutrophils were readily recruited in vivo to the site of infection in an intact host and that spore phagocytosis can be observed in real-time in vivo. While exploring innate immune effector recruitment dynamics, we discovered the formation of phagocyte clusters in response to fungal spores that potentially play a role in fungal spore dissemination. Spores failed to activate pro-inflammatory gene expression by 6 h post-infection in both infection models. After 24 h, induction of a pro-inflammatory response was observed only in hindbrain ventricle infections. Only a weak pro-inflammatory response was initiated after spore injection into the swim bladder during the same time frame. In the future, the zebrafish larva as a live whole

  19. A Rare Early-type Star Revealed in the Wing of the Small Magellanic Cloud

    NASA Astrophysics Data System (ADS)

    Evans, C. J.; Hainich, R.; Oskinova, L. M.; Gallagher, J. S., III; Chu, Y.-H.; Gruendl, R. A.; Hamann, W.-R.; Hénault-Brunet, V.; Todt, H.

    2012-07-01

    Sk 183 is the visually brightest star in the N90 nebula, a young star-forming region in the Wing of the Small Magellanic Cloud (SMC). We present new optical spectroscopy from the Very Large Telescope which reveals Sk 183 to be one of the most massive O-type stars in the SMC. Classified as an O3-type dwarf on the basis of its nitrogen spectrum, the star also displays broadened He I absorption, which suggests a later type. We propose that Sk 183 has a composite spectrum and that it is similar to another star in the SMC, MPG 324. This brings the number of rare O2- and O3-type stars known in the whole of the SMC to a mere four. We estimate physical parameters for Sk 183 from analysis of its spectrum. For a single-star model, we estimate an effective temperature of 46 ± 2 kK, a low mass-loss rate of ~10-7 M ⊙ yr-1, and a spectroscopic mass of 46+9 -8 M ⊙ (for an adopted distance modulus of 18.7 mag to the young population in the SMC Wing). An illustrative binary model requires a slightly hotter temperature (~47.5 kK) for the primary component. In either scenario, Sk 183 is the earliest-type star known in N90 and will therefore be the dominant source of hydrogen-ionizing photons. This suggests Sk 183 is the primary influence on the star formation along the inner edge of the nebula.

  20. NanoSIMS Reveals New Structural and Elemental Signatures of Early Life

    NASA Technical Reports Server (NTRS)

    Oehler, Dorothy Z.; Mostefaoui, Smail; Meibom, Anders; Selo, Madeleine; Robert, Francois; McKay, David S.

    2006-01-01

    The young technology of NanoSIMS is unlocking new information from organic matter in ancient sediments. We have used this technique to characterize sub-micron scale element composition of Proterozoic organics that are clearly biogenic as a guide for interpreting problematic structures in terrestrial or extraterrestrial samples. We used the NanoSIMS 50 of the National Museum of Natural History in Paris to map carbon, nitrogen (as CN), and sulfur in organic structures from the approximately 0.8 Ga Bitter Springs Formation. We analyzed spheroidal and filamentous microfossils as well as organic laminae that appeared amorphous by optical and scanning electron microscopy. In clear-cut microfossils, a coincidence between optical images and NanoSIMS element maps suggests a biological origin for the mapped carbon, sulfur, and nitrogen; this conclusion is supported by high resolution NanoSIMS maps showing identical spatial distributions of C, CN and S. High resolution images also demonstrate distinctive nano structure of the filaments and spheroids. In the amorphous laminae, NanoSIMS reveals morphologies reminiscent of compressed microfossils. Distinct CN/C ratios of the spheroids, filaments, and laminae may reflect their biological precursors (cell walls, cyanobacterial sheaths, and microbial communities/biofilms, respectively). Similar amorphous laminae comprise a preponderance of the organic matter in many Precambrian deposits. Thus it is possible that NanoSIMS will provide fresh insight into a large body of previously uninterpretable material. Additionally, NanoSIMS analysis may establish new biosignatures that will be helpful for assessing the origin and biogenicity of controversial Archean structures and any organic materials that may occur in Martian or other extraterrestrial samples.

  1. Early stages of carbonate mineralization revealed from molecular simulations: Implications for biomineral formation

    NASA Astrophysics Data System (ADS)

    Wallace, A. F.; DeYoreo, J.; Banfield, J. F.

    2011-12-01

    calcite-type lattice is also apparent. Continued growth results in expansion of the dehydrated core, however, complete desolvation and incorporation of cations into the growing carbonate phase is not achieved until the cluster grows to ~1.2 nm. Exploration of the system free energy along the crystallization path reveals "special" cluster sizes that correlate with ion desolvation milestones. The formation of these species comprise critical bottlenecks on the energy landscape and for the establishment of order within the growing clusters.

  2. Proteomic profiling reveals crucial retinal protein alterations in the early phase of an experimental glaucoma model.

    PubMed

    Anders, Fabian; Teister, Julia; Funke, Sebstian; Pfeiffer, Norbert; Grus, Franz; Solon, Thanos; Prokosch, Verena

    2017-07-01

    Clinical glaucoma is difficult to assess in terms of molecular pathophysiology, prompting studies in experimental models of glaucoma. The purpose of this study was to investigate quantitative changes in retinal protein expression at the onset of experimental glaucoma in rats. Analyzing the proteome provides a suitable tool to decipher the pathophysiological processes in glaucomatous degeneration. Thermic cauterization of episcleral veins was utilized to elevate the intraocular pressure in Sprague Dawley rats. Morphological changes were surveyed on a cellular level with a staining of Brn3a-positive cells. The retinal nerve fiber layer was investigated using optical coherence tomography (OCT, Heidelberg Engineering) and the optic nerve was analyzed by an axonal grading system. Mass spectrometry-featured quantitative proteomics and immunohistochemical staining was used to identify specifically altered proteins in the course of intraocular pressure elevation and initial neurodegeneration. Proteomic data were further analyzed with Ingenuity Pathway Analysis and Cytoscape to analyze further molecular associations. The intraocular pressure rose significantly (p < 0.001) for the follow-up period of 3 weeks after which animals were sacrificed. Eyes exposed to an elevated intraocular pressure showed an initial decrease of retinal ganglion cells, retinal nerve fiber layer (p < 0.05) and an impairment of the optic nerve (p < 0.01). Mass spectrometry led to the identification and quantification of 931 retinal proteins, whereas 32 were considerably altered. Bioinformatics-assisted clustering revealed that a majority of these proteins are functionally associated with cell differentiation, apoptosis and stress response. The creation of an interactive protein network showed that numerous altered proteins are connected regarding their cellular function. Protein kinase b, mitogen-activated protein kinase 1 and the NF-κB complex seem to be essential molecules in this context

  3. Early post-metamorphic, Carboniferous blastoid reveals the evolution and development of the digestive system in echinoderms.

    PubMed

    Rahman, Imran A; Waters, Johnny A; Sumrall, Colin D; Astolfo, Alberto

    2015-10-01

    Inferring the development of the earliest echinoderms is critical to uncovering the evolutionary assembly of the phylum-level body plan but has long proven problematic because early ontogenetic stages are rarely preserved as fossils. Here, we use synchrotron tomography to describe a new early post-metamorphic blastoid echinoderm from the Carboniferous (approx. 323 Ma) of China. The resulting three-dimensional reconstruction reveals a U-shaped tubular structure in the fossil interior, which is interpreted as the digestive tract. Comparisons with the developing gut of modern crinoids demonstrate that crinoids are an imperfect analogue for many extinct groups. Furthermore, consideration of our findings in a phylogenetic context allows us to reconstruct the evolution and development of the digestive system in echinoderms more broadly; there was a transition from a straight to a simple curved gut early in the phylum's evolution, but additional loops and coils of the digestive tract (as seen in crinoids) were not acquired until much later. © 2015 The Author(s).

  4. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis

    PubMed Central

    Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

    2014-01-01

    Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P<0.01), compared to normal controls. More than 80% of the VEGFR-2 in the diabetic retina was in the capillaries, compared to 47% in normal controls (P<0.01). Angiography in rabbit retinas revealed microvascular capillaries to be the location for VEGF-A-induced leakage, as expressed by significantly higher rate of fluorophore spreading with VEGF-A injection when compared to vehicle control (26±2 vs. 3±1 μm/s, P<0.05). Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals but not in normal controls. Macular vessels from diabetic patients (n=7) showed significantly more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral retinal regions of the same retinas (P<0.01 in both cases). Here we introduce a new approach for early diagnosis of DR and VEGFR-2 as a molecular marker. VEGFR-2 could become a key diagnostic target, one that might help to prevent retinal vascular leakage and proliferation in diabetic patients.—Sun, D., Nakao, S., Xie, F., Zandi, S., Bagheri, A., Kanavi, M. R., Samiei, S., Soheili, Z.-S., Frimmel, S., Zhang, Z., Ablonczy, Z., Ahmadieh, H., Hafezi-Moghadam, A. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis. PMID:24903276

  5. Ancient DNA reveals a migration of the ancient Di-qiang populations into Xinjiang as early as the early Bronze Age.

    PubMed

    Gao, Shi-Zhu; Zhang, Ye; Wei, Dong; Li, Hong-Jie; Zhao, Yong-Bin; Cui, Yin-Qiu; Zhou, Hui

    2015-05-01

    Xinjiang is at the crossroads between East and West Eurasia, and it harbors a relatively complex genetic history. In order to better understand the population movements and interactions in this region, mitochondrial and Y chromosome analyses on 40 ancient human remains from the Tianshanbeilu site in eastern Xinjiang were performed. Twenty-nine samples were successfully assigned to specific mtDNA haplogroups, including the west Eurasian maternal lineages of U and W and the east Eurasian maternal lineages of A, C, D, F, G, Z, M7, and M10. In the male samples, two Y chromosome haplogroups, C* and N1 (xN1a, N1c), were successfully assigned. Our mitochondrial and Y-chromosomal DNA analyses combined with the archaeological studies revealed that the Di-qiang populations from the Hexi Corridor had migrated to eastern Xinjiang and admixed with the Eurasian steppe populations in the early Bronze Age. © 2014 Wiley Periodicals, Inc.

  6. An epidemiological study of blindness in an Indian rural community.

    PubMed Central

    Srivastava, R N; Verma, B L

    1978-01-01

    A house-to-house survey of blindness in an Indian rural community covering a population of 20 134 in 12 villages revealed a prevalence rate of 35 blind and 144 partially blind persons per 10 000 population. Blindness was significantly associated with the age, sex, marital status, occupation, and socioeconomic status of the respondents. Caratact, glaucoma, smallpox and trachoma were the main causes of blindness. Preventive measures can reduce the toll of blindness in such a community. PMID:681587

  7. Transversus abdominis plane block reduces morphine consumption in the early postoperative period following microsurgical abdominal tissue breast reconstruction: a double-blind, placebo-controlled, randomized trial.

    PubMed

    Zhong, Toni; Ojha, M; Bagher, Shaghayegh; Butler, Kate; Srinivas, Coimbatore; McCluskey, Stuart A; Clarke, Hance; O'Neill, Anne C; Novak, Christine B; Hofer, Stefan O P

    2014-11-01

    The analgesic efficacy of the transversus abdominis plane peripheral nerve block following abdominal tissue breast reconstruction has not been studied in a randomized controlled trial. The authors conducted a double-blind, placebo-controlled, 1:1 allocation, two-arm parallel group, superiority design, randomized controlled trial in patients undergoing microsurgical abdominally based breast reconstruction. Intraoperatively, epidural catheters were inserted under direct vision through the triangle of Petit on both sides of the abdomen into the transversus abdominis plane just before rectus fascial closure. Patients received either bupivacaine (study group) or saline (placebo group) through the catheters for 2 postoperative days. All patients received hydromorphone by means of a patient-controlled analgesic pump. The primary outcome was the difference in the parenteral opioid consumption on each postoperative day between the groups. The secondary outcome measures included the following: total in-hospital opioid; antinausea medication; pain, nausea, and sedation scores; Quality of Recovery Score; time to ambulation; and hospital stay duration. Between September of 2011 and June of 2013, 93 patients were enrolled: 49 received bupivacaine and 44 received saline. There were 11 postoperative complications (13 percent); none were related to the catheter. Primary outcomes were completed by 85 of 93 patients (91.3 percent); the mean parenteral morphine consumption was significantly reduced on postoperative day 1 in the bupivacaine group (20.7±20.1 mg) compared with 30.0±19.1 mg in the control group (p=0.02). There were no significant differences in secondary outcomes. Following abdominally based breast reconstruction, transversus abdominis plane peripheral nerve block is safe and significantly reduces morphine consumption in the early postoperative period. Therapeutic, II.

  8. Comparison of Mifepristone Followed by Misoprostol with Misoprostol Alone for Treatment of Early Pregnancy Failure: A Randomized Double-Blind Placebo-Controlled Trial.

    PubMed

    Sinha, Priya; Suneja, Amita; Guleria, Kiran; Aggarwal, Richa; Vaid, Neelam B

    2018-02-01

    To compare the efficacy and safety of mifepristone followed by misoprostol with misoprostol alone in the management of early pregnancy failure (EPF). A randomized double-blind placebo-controlled clinical trial. Ninety-two women with EPF ≤12 weeks were recruited and randomly allocated to receive either mifepristone 200 mg ( n  = 46) or placebo ( n  = 46). Forty-eight hours later, patients in both the groups were given 800 µg misoprostol per-vaginum. If no expulsion occurred within 4 h, repeat doses of 400 µg misoprostol were given orally at 3-hourly interval to a maximum of 2 doses in women ≤9 weeks by scan and 4 doses in women >9 weeks by scan. Pre-treatment of misoprostol with mifepristone significantly increased the complete abortion rate (86.7 vs. 57.8%, p  = 0.009) and, hence, reduced the need for surgical evacuation (13.3 vs. 42.2%, p  = 0.002), induction to expulsion interval (4.74 ± 2.24 vs. 8.03 ± 2.77 h, p  = 0.000), mean number of additional doses of misoprostol required (0.68 vs. 1.91, p  = 0.000), and side effects. Use of mifepristone prior to misoprostol in EPF significantly improves the efficacy and reduces the side effects of misoprostol alone.

  9. Impact of hyperventilation on stimulus efficiency during the early phase of an electroconvulsive therapy course: a randomized double-blind study.

    PubMed

    Mayur, Prashanth; Bray, Amanda; Fernandes, Joanne; Bythe, Karen; Gilbett, David

    2010-06-01

    The question whether hyperventilation during electroconvulsive therapy (ECT) can improve stimulus efficiency is as yet unanswered. Twenty-five consecutive consenting patients (N = 25) with major depression who were administered ECT entered into the study. Right unilateral ECT at thrice the threshold dose was administered using Mecta spECTrum 5000Q (Mecta Corp, Lake Oswego, Ore), with standard titration procedures and stimulus configurations. At the second ECT session, they were randomly allocated to ECT either with hyperventilation or with no hyperventilation. Hyperventilation was actively administered by an anesthetist just after anesthetic paralysis and before the ECT stimulus during the second, third, and fourth ECT sessions. Assessments were double-blind and performed at baseline and 24 to 48 hours after the fourth ECT session. Time to reorient after ECT was assessed during the first up to the fourth ECT session. Ictal electroencephalogram (EEG) quality was visually assessed using standard scales. There were no significant differences across the 2 groups about depression severity and global cognitive impact. However, the orientation time was 34% longer among those who did not receive hyperventilation. The ratio of orientation time without hyperventilation to that with hyperventilation equals 1.34 (95% confidence interval, 0.94-1.92; P = 0.103). There was a significant increase in threshold over time across both groups (mean difference, 16.4; SE, 5.5; P = 0.006) with no significant main effect for the groups (P = 0.399). There were no significant group differences in the EEG quality. The addition of hyperventilation during the early phase of the ECT course shows a trend to lessen the impact on immediate orientation without impeding clinical response. This does not seem to be mediated by differential threshold changes or change to the ictal EEG quality.

  10. How does experience modulate auditory spatial processing in individuals with blindness?

    PubMed

    Tao, Qian; Chan, Chetwyn C H; Luo, Yue-jia; Li, Jian-jun; Ting, Kin-hung; Wang, Jun; Lee, Tatia M C

    2015-05-01

    Comparing early- and late-onset blindness in individuals offers a unique model for studying the influence of visual experience on neural processing. This study investigated how prior visual experience would modulate auditory spatial processing among blind individuals. BOLD responses of early- and late-onset blind participants were captured while performing a sound localization task. The task required participants to listen to novel "Bat-ears" sounds, analyze the spatial information embedded in the sounds, and specify out of 15 locations where the sound would have been emitted. In addition to sound localization, participants were assessed on visuospatial working memory and general intellectual abilities. The results revealed common increases in BOLD responses in the middle occipital gyrus, superior frontal gyrus, precuneus, and precentral gyrus during sound localization for both groups. Between-group dissociations, however, were found in the right middle occipital gyrus and left superior frontal gyrus. The BOLD responses in the left superior frontal gyrus were significantly correlated with accuracy on sound localization and visuospatial working memory abilities among the late-onset blind participants. In contrast, the accuracy on sound localization only correlated with BOLD responses in the right middle occipital gyrus among the early-onset counterpart. The findings support the notion that early-onset blind individuals rely more on the occipital areas as a result of cross-modal plasticity for auditory spatial processing, while late-onset blind individuals rely more on the prefrontal areas which subserve visuospatial working memory.

  11. Can Valeriana officinalis root extract prevent early postoperative cognitive dysfunction after CABG surgery? A randomized, double-blind, placebo-controlled trial.

    PubMed

    Hassani, Soghra; Alipour, Abbas; Darvishi Khezri, Hadi; Firouzian, Abolfazl; Emami Zeydi, Amir; Gholipour Baradari, Afshin; Ghafari, Rahman; Habibi, Wali-Allah; Tahmasebi, Homeyra; Alipour, Fatemeh; Ebrahim Zadeh, Pooneh

    2015-03-01

    We hypothesized that valerian root might prevent cognitive dysfunction in coronary artery bypass graft (CABG) surgery patients through stimulating serotonin receptors and anti-inflammatory activity. The aim of this study was to evaluate the effect of Valeriana officinalis root extract on prevention of early postoperative cognitive dysfunction after on-pump CABG surgery. In a randomized, double-blind, placebo-controlled trial, 61 patients, aged between 30 and 70 years, scheduled for elective CABG surgery using cardiopulmonary bypass (CPB), were recruited into the study. Patients were randomly divided into two groups who received either one valerian capsule containing 530 mg of valerian root extract (1,060 mg/daily) or placebo capsule each 12 h for 8 weeks, respectively. For all patients, cognitive brain function was evaluated before the surgery and at 10-day and 2-month follow-up by Mini Mental State Examination (MMSE) test. Mean MMSE score decreased from 27.03 ± 2.02 in the preoperative period to 26.52 ± 1.82 at the 10th day and then increased to 27.45 ± 1.36 at the 60th day in the valerian group. Conversely, its variation was reduced significantly after 60 days in the placebo group, 27.37 ± 1.87 at the baseline to 24 ± 1.91 at the 10th day, and consequently slightly increased to 24.83 ± 1.66 at the 60th day. Valerian prophylaxis reduced odds of cognitive dysfunction compared to placebo group (OR = 0.108, 95 % CI 0.022-0.545). We concluded that, based on this study, the cognitive state of patients in the valerian group was better than that in the placebo group after CABG; therefore, it seems that the use of V. officinalis root extract may prevent early postoperative cognitive dysfunction after on-pump CABG surgery.

  12. Effect of parecoxib sodium pretreatment combined with dexmedetomidine on early postoperative cognitive dysfunction in elderly patients after shoulder arthroscopy: A randomized double blinded controlled trial.

    PubMed

    Lu, Jian; Chen, Gang; Zhou, Hongmei; Zhou, Qinghe; Zhu, Zhipeng; Wu, Cheng

    2017-09-01

    To evaluate effect of parecoxib sodium pretreatment combined with dexmedetomidine on early postoperative cognitive dysfunction in elderly patients after shoulder arthroscopy. Randomized, double-blind study. University-affiliated teaching hospital. One hundred and fifty-two elderly patients scheduled for shoulder arthroscopy. At 15min before the induction of anesthesia, 152 patients received intravenously parecoxib sodium 40mg and dexmedetomidine at a dose of 0.5μg/kg over 15min, followed by a continuous infusion at a rate of 0.5μg/kg/h until the end of surgery. Then all patients who received postoperative patient-controlled intravenous analgesia were divided 2 groups: sufentanil(0.04μg/kg/h, S group), sufentanil (0.04μg/kg/h) plus dexmedetomidine(0.06μg/kg/h) (SD group). The mini-mental status examination score in SD group was significantly higher than S group at 1, 2 and 7days after surgery. The incidence of postoperative cognitive dysfunction during 7days after surgery in S and SD groups was respectively 17.1% and 6.7%. Compared with the S group, the visual analogue scale scores at rest and upon movement were significantly lower at 6, 14, 24, 36 and 48h after surgery in SD group; analgesia pump liquid amount during 24h after surgery and number of rescue analgesia during 48h after surgery were significantly lower in SD group. Jugular venous oxygen partial pressure and jugular venous oxygen saturation values in SD group were significantly higher than S group at postoperative 24h. The occurrence of nausea and vomiting within 48h after surgery in SD group were significantly lower than S group. We found no complications including respiratory depression and sinus bradycardia within 48h after surgery in all patients. Parecoxib sodium pretreatment combined with dexmedetomidine could reduce the incidence of early postoperative cognitive dysfunction in elderly patients. This might be related to the improvement of postoperative analgesia effect and cerebral oxygen

  13. A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories

    PubMed Central

    Akimoto, Chizuru; Volk, Alexander E; van Blitterswijk, Marka; Van den Broeck, Marleen; Leblond, Claire S; Lumbroso, Serge; Camu, William; Neitzel, Birgit; Onodera, Osamu; van Rheenen, Wouter; Pinto, Susana; Weber, Markus; Smith, Bradley; Proven, Melanie; Talbot, Kevin; Keagle, Pamela; Chesi, Alessandra; Ratti, Antonia; van der Zee, Julie; Alstermark, Helena; Birve, Anna; Calini, Daniela; Nordin, Angelica; Tradowsky, Daniela C; Just, Walter; Daoud, Hussein; Angerbauer, Sabrina; DeJesus-Hernandez, Mariely; Konno, Takuya; Lloyd-Jani, Anjali; de Carvalho, Mamede; Mouzat, Kevin; Landers, John E; Veldink, Jan H; Silani, Vincenzo; Gitler, Aaron D; Shaw, Christopher E; Rouleau, Guy A; van den Berg, Leonard H; Van Broeckhoven, Christine; Rademakers, Rosa; Andersen, Peter M; Kubisch, Christian

    2014-01-01

    Background The GGGGCC-repeat expansion in C9orf72 is the most frequent mutation found in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Most of the studies on C9orf72 have relied on repeat-primed PCR (RP-PCR) methods for detection of the expansions. To investigate the inherent limitations of this technique, we compared methods and results of 14 laboratories. Methods The 14 laboratories genotyped DNA from 78 individuals (diagnosed with ALS or FTD) in a blinded fashion. Eleven laboratories used a combination of amplicon-length analysis and RP-PCR, whereas three laboratories used RP-PCR alone; Southern blotting techniques were used as a reference. Results Using PCR-based techniques, 5 of the 14 laboratories got results in full accordance with the Southern blotting results. Only 50 of the 78 DNA samples got the same genotype result in all 14 laboratories. There was a high degree of false positive and false negative results, and at least one sample could not be genotyped at all in 9 of the 14 laboratories. The mean sensitivity of a combination of amplicon-length analysis and RP-PCR was 95.0% (73.9–100%), and the mean specificity was 98.0% (87.5–100%). Overall, a sensitivity and specificity of more than 95% was observed in only seven laboratories. Conclusions Because of the wide range seen in genotyping results, we recommend using a combination of amplicon-length analysis and RP-PCR as a minimum in a research setting. We propose that Southern blotting techniques should be the gold standard, and be made obligatory in a clinical diagnostic setting. PMID:24706941

  14. The blind men meet the elephant at the dam: Alternative spatial and taxonomic components reveal different insights about how low-head dams impact fish biodiversity

    USGS Publications Warehouse

    Fencl, Jane S.; Mather, Martha E.; Smith, Joseph M.; Hitchman, Sean M.

    2017-01-01

    Dams are ubiquitous environmental impacts that threaten aquatic ecosystems. The ability to compare across research studies is essential to conserve the native biodiversity that is impacted by the millions of low‐head dams that currently fragment streams and rivers. Here, we identify a previously unaddressed obstacle that impedes this generalization. Specifically, divergent spatial and taxonomic approaches that result from different conceptualizations of the dam‐biodiversity problem can produce conflicting science‐based conclusions about the same dam impact. In this research, using the same dammed and undammed sites, we evaluated the scientific generality of different conceptualizations of the dam‐biodiversity problem. We compared two different but commonly used spatial approaches—(1) above dam–below dam vs. (2) undammed–dammed comparisons—and 11 different, commonly used taxonomic approaches (three assemblage summaries, eight guilds). Sites above the dam structure had less diverse fish assemblages than sites below dams, whereas sites below the dam structure were similar to undammed sites. Thus, spatial approach 1 detected a large dam effect and spatial approach 2 detected a small dam effect. Similarly, some taxonomic responses (species richness, diversity, abundance, and number of guilds) detected large dam effects; other responses detected small (riffle specialist guild) or no dam effects (pool generalists). In summary, our results showed that how the problem was framed altered scientific conclusions and created different dam realities. The metaphor of how individual blind men disagree about the structure of an elephant, based on examinations of different body parts, reinforces the need for a coordinated, holistic perspective on dam research. Although no single approach is adequate for all problems, identifying the form, consequences of, and relationships among different research conceptualizations will set the stage for future syntheses of dam

  15. Blind Ambition

    ERIC Educational Resources Information Center

    Olson, Catherine Applefeld

    2009-01-01

    No matter how dedicated they may be, some teachers are daunted by extreme challenges. Carol Agler, music director at the Ohio State School for the Blind (OSSB), is not one of those teachers. Since joining the OSSB staff 11 years ago, Agler has revived the school's long-dormant band program and created its first marching band. Next January, she…

  16. Blindness Clues

    ERIC Educational Resources Information Center

    Science Teacher, 2005

    2005-01-01

    Age-related macular degeneration is the leading cause of blindness in older adults, yet researchers are still in the dark about many of the factors that cause this incurable disease. But new insight from University of Florida (UF) and German researchers about a genetic link between rhesus monkeys with macular degeneration and humans could unlock…

  17. Early transcriptional and epigenetic regulation of CD8+ T cell differentiation revealed by single-cell RNA-seq

    PubMed Central

    Kakaradov, Boyko; Arsenio, Janilyn; Widjaja, Christella E.; He, Zhaoren; Aigner, Stefan; Metz, Patrick J.; Yu, Bingfei; Wehrens, Ellen J.; Lopez, Justine; Kim, Stephanie H.; Zuniga, Elina I.; Goldrath, Ananda W.; Chang, John T.; Yeo, Gene W.

    2017-01-01

    SUMMARY During microbial infection, responding CD8+ T lymphocytes differentiate into heterogeneous subsets that together provide immediate and durable protection. To elucidate the dynamic transcriptional changes that underlie this process, we applied a single-cell RNA sequencing approach and analyzed individual CD8+ T lymphocytes sequentially throughout the course of a viral infection in vivo. Our analyses revealed a striking transcriptional divergence among cells that had undergone their first division and identified previously unknown molecular determinants controlling CD8+ T lymphocyte fate specification. These findings suggest a model of terminal effector cell differentiation initiated by an early burst of transcriptional activity and subsequently refined by epigenetic silencing of transcripts associated with memory lymphocytes, highlighting the power and necessity of single-cell approaches. PMID:28218746

  18. Local and Global Processing in Blind and Sighted Children in a Naming and Drawing Task

    ERIC Educational Resources Information Center

    Puspitawati, Ira; Jebrane, Ahmed; Vinter, Annie

    2014-01-01

    This study investigated the spatial analysis of tactile hierarchical patterns in 110 early-blind children aged 6-8 to 16-18 years, as compared to 90 blindfolded sighted children, in a naming and haptic drawing task. The results revealed that regardless of visual status, young children predominantly produced local responses in both tasks, whereas…

  19. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis.

    PubMed

    Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

    2014-09-01

    Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P<0.01), compared to normal controls. More than 80% of the VEGFR-2 in the diabetic retina was in the capillaries, compared to 47% in normal controls (P<0.01). Angiography in rabbit retinas revealed microvascular capillaries to be the location for VEGF-A-induced leakage, as expressed by significantly higher rate of fluorophore spreading with VEGF-A injection when compared to vehicle control (26±2 vs. 3±1 μm/s, P<0.05). Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals but not in normal controls. Macular vessels from diabetic patients (n=7) showed significantly more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral retinal regions of the same retinas (P<0.01 in both cases). Here we introduce a new approach for early diagnosis of DR and VEGFR-2 as a molecular marker. VEGFR-2 could become a key diagnostic target, one that might help to prevent retinal vascular leakage and proliferation in diabetic patients. © FASEB.

  20. Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection

    NASA Astrophysics Data System (ADS)

    Chu, Li-Wei; Huang, Yi-Lung; Lee, Jin-Hui; Huang, Long-Ying; Chen, Wei-Jun; Lin, Ya-Hsuan; Chen, Jyun-Yu; Xiang, Rui; Lee, Chau-Hwang; Ping, Yueh-Hsin

    2014-01-01

    Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV.

  1. Absolute pitch: evidence for early cognitive facilitation during passive listening as revealed by reduced P3a amplitudes.

    PubMed

    Rogenmoser, Lars; Elmer, Stefan; Jäncke, Lutz

    2015-03-01

    Absolute pitch (AP) is the rare ability to identify or produce different pitches without using reference tones. At least two sequential processing stages are assumed to contribute to this phenomenon. The first recruits a pitch memory mechanism at an early stage of auditory processing, whereas the second is driven by a later cognitive mechanism (pitch labeling). Several investigations have used active tasks, but it is unclear how these two mechanisms contribute to AP during passive listening. The present work investigated the temporal dynamics of tone processing in AP and non-AP (NAP) participants by using EEG. We applied a passive oddball paradigm with between- and within-tone category manipulations and analyzed the MMN reflecting the early stage of auditory processing and the P3a response reflecting the later cognitive mechanism during the second processing stage. Results did not reveal between-group differences in MMN waveforms. By contrast, the P3a response was specifically associated with AP and sensitive to the processing of different pitch types. Specifically, AP participants exhibited smaller P3a amplitudes, especially in between-tone category conditions, and P3a responses correlated significantly with the age of commencement of musical training, suggesting an influence of early musical exposure on AP. Our results reinforce the current opinion that the representation of pitches at the processing level of the auditory-related cortex is comparable among AP and NAP participants, whereas the later processing stage is critical for AP. Results are interpreted as reflecting cognitive facilitation in AP participants, possibly driven by the availability of multiple codes for tones.

  2. Efficacy of early administration of escitalopram on depressive and emotional symptoms and neurological dysfunction after stroke: a multicentre, double-blind, randomised, placebo-controlled study.

    PubMed

    Kim, Jong S; Lee, Eun-Jae; Chang, Dae-Il; Park, Jong-Ho; Ahn, Seong Hwan; Cha, Jae-Kwan; Heo, Ji Hoe; Sohn, Sung-Il; Lee, Byung-Chul; Kim, Dong-Eog; Kim, Hahn Young; Kim, Seongheon; Kwon, Do-Young; Kim, Jei; Seo, Woo-Keun; Lee, Jun; Park, Sang-Won; Koh, Seong-Ho; Kim, Jin Young; Choi-Kwon, Smi

    2017-01-01

    Mood and emotional disturbances are common in patients with stroke, and adversely affect the clinical outcome. We aimed to evaluate the efficacy of early administration of escitalopram to reduce moderate or severe depressive symptoms and improve emotional and neurological dysfunction in patients with stroke. This was a placebo controlled, double-blind trial done at 17 centres in South Korea. Patients who had had an acute stroke within the past 21 days were randomly assigned in a 1:1 ratio to receive oral escitalopram (10 mg/day) or placebo for 3 months. Randomisation was done with permuted blocks stratified by centre, via a web-based system. The primary endpoint was the frequency of moderate or severe depressive symptoms (Montgomery-Åsberg Depression Rating Scale [MADRS] ≥16). Endpoints were assessed at 3 months after randomisation in the full analysis set (patients who took study medication and underwent assessment of primary endpoint after randomisation), in all patients who were enrolled and randomly assigned (intention to treat), and in all patients who completed the trial (per-protocol analysis). This trial is registered with ClinicalTrials.gov, number NCT01278498. Between Jan 27, 2011, and June 30, 2014, 478 patients were assigned to placebo (n=237) or escitalopram (n=241); 405 were included in the full analysis set (195 in the placebo group, 210 in the escitalopram group). The primary outcome did not differ by study group in the full analysis set (25 [13%] patients in the placebo group vs 27 [13%] in the escitalopram group; odds ratio [OR] 1·00, 95% CI 0·56-1·80; p>0·99) or in the intention-to-treat analysis (34 [14%] vs 35 [15%]; OR 1·01, 95% CI 0·61-1·69, p=0·96). The study medication was generally well tolerated; the most common adverse events were constipation (14 [6%] patients who received placebo vs 14 [6%] who received escitalopram), muscle pain (16 [7%] vs ten [4%]), and insomnia (12 [5%] vs 12 [5%]). Diarrhoea was more common in the

  3. Acute Blindness.

    PubMed

    Meekins, Jessica M

    2015-09-01

    Sudden loss of vision is an ophthalmic emergency with numerous possible causes. Abnormalities may occur at any point within the complex vision pathway, from retina to optic nerve to the visual center in the occipital lobe. This article reviews specific prechiasm (retina and optic nerve) and cerebral cortical diseases that lead to acute blindness. Information regarding specific etiologies, pathophysiology, diagnosis, treatment, and prognosis for vision is discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Childhood Fears among Children Who Are Blind: The Perspective of Teachers Who Are Blind

    ERIC Educational Resources Information Center

    Al-Zboon, Eman

    2017-01-01

    The aim of this study was to investigate childhood fears in children who are blind from the perspective of teachers who are blind. The study was conducted in Jordan. Forty-six teachers were interviewed. Results revealed that the main fear content in children who are blind includes fear of the unknown; environment-, transportation- and…

  5. Rbm20-deficient cardiogenesis reveals early disruption of RNA processing and sarcomere remodeling establishing a developmental etiology for dilated cardiomyopathy.

    PubMed

    Beraldi, Rosanna; Li, Xing; Martinez Fernandez, Almudena; Reyes, Santiago; Secreto, Frank; Terzic, Andre; Olson, Timothy M; Nelson, Timothy J

    2014-07-15

    Dilated cardiomyopathy (DCM) due to mutations in RBM20, a gene encoding an RNA-binding protein, is associated with high familial penetrance, risk of progressive heart failure and sudden death. Although genetic investigations and physiological models have established the linkage of RBM20 with early-onset DCM, the underlying basis of cellular and molecular dysfunction is undetermined. Modeling human genetics using a high-throughput pluripotent stem cell platform was herein designed to pinpoint the initial transcriptome dysfunction and mechanistic corruption in disease pathogenesis. Tnnt2-pGreenZeo pluripotent stem cells were engineered to knockdown Rbm20 (shRbm20) to determine the cardiac-pathogenic phenotype during cardiac differentiation. Intracellular Ca(2+) transients revealed Rbm20-dependent alteration in Ca(2+) handling, coinciding with known pathological splice variants of Titin and Camk2d genes by Day 24 of cardiogenesis. Ultrastructural analysis demonstrated elongated and thinner sarcomeres in the absence of Rbm20 that is consistent with human cardiac biopsy samples. Furthermore, Rbm20-depleted transcriptional profiling at Day 12 identified Rbm20-dependent dysregulation with 76% of differentially expressed genes linked to known cardiac pathology ranging from primordial Nkx2.5 to mature cardiac Tnnt2 as the initial molecular aberrations. Notably, downstream consequences of Rbm20-depletion at Day 24 of differentiation demonstrated significant dysregulation of extracellular matrix components such as the anomalous overexpression of the Vtn gene. By using the pluripotent stem cell platform to model human cardiac disease according to a stage-specific cardiogenic roadmap, we established a new paradigm of familial DCM pathogenesis as a developmental disorder that is patterned during early cardiogenesis and propagated with cellular mechanisms of pathological cardiac remodeling. © The Author 2014. Published by Oxford University Press. All rights reserved. For

  6. Analysis of NUAK1 and NUAK2 expression during early chick development reveals specific patterns in the developing head.

    PubMed

    Bekri, Abdelhamid; Billaud, Marc; Thélu, Jacques

    2014-01-01

    Several human diseases are associated with the NUAK1 and NUAK2 genes. These genes encode kinases, members of the AMPK-related kinases (ARK) gene family. Both NUAK1 and NUAK2 are known targets of the serine threonine kinase LKB1, a tumor suppressor involved in regulating cell polarity. While much is known about their functions in disease, their expression pattern in normal development has not been extensively studied. Here, we present the expression patterns for NUAK1 and NUAK2 in the chick during early-stage embryogenesis, until day 3 (Hamburger and Hamilton stage HH20). Several embryonic structures, in particular the nascent head, showed distinct expression levels. NUAK1 expression was first detected at stage HH6 in the rostral neural folds. It was then expressed (HH7-11) throughout the encephalalon, predominantly in the telencephalon and mesencephalon. NUAK1 expression was also detected in the splanchnic endoderm area at HH8-10, and in the vitellin vein derived from this area, but not in the heart. NUAK2 expression was first detected at stage HH6 in the neural folds. It was then found throughout the encephalon at stage HH20. Particular attention was paid in this study to the dorsal ectoderm at stages HH7 and HH8, where a local deficit or accumulation of NUAK2 mRNA were found to correlate with the direction of curvature of the neural plate. This is the first description of NUAK1 and NUAK2 expression patterns in the chick during early development; it reveals non-identical expression profiles for both genes in neural development.

  7. Longitudinal assessment of retinal structure and function reveals a rod-cone degeneration in a guinea pig model initially presented as night blind.

    PubMed

    Racine, Julie; Joly, Sandrine; Lachapelle, Pierre

    2011-08-01

    We have previously reported a naturally occurring retinopathy in a population of guinea pigs, where the affected animals presented a defect of the rod-mediated vision. The purpose of this study was to investigate if the mutants were affected with a stationary or degenerative retinopathy and to identify the cellular origin of this unique disorder. Electroretinogram (ERG) [postnatal day 1 (P1) to P450], light (LM) and electron microscopy (EM) [P5, P150, P450], and immunohistochemistry [P30, P150, P450] were evaluated from normal and mutant animals. Irrespective of age, the scotopic ERGs of mutants could only be evoked by bright flashes, and the resulting ERGs were of photopic waveform. Interestingly, the amplitude of the cone and the rod/cone a-waves was always of smaller amplitude in mutants, but this difference tended to decrease with age. In contrast, the b-waves were of larger amplitude than normal in photopic ERGs obtained prior to age 25 (days) and prior to age 10 for rod/cone ERGs. LM revealed, in mutants, an absence of the outer segment layer (OSL) with a reduction in the outer nuclear layer (ONL) thickness. EM disclosed the presence of cone outer segment (OS) while no rod OS could be evidenced. Immunohistochemistry revealed the presence of rhodopsin, both cone opsins as well as normal synaptophysin immunoreactivity. Finally, neither the retinal structure nor the function in the mutants achieved normal development. Results suggest that mutant animals are suffering from a degenerative retinal disorder that affects the structure and function of rods and cones.

  8. Brain morphometry in blind and sighted subjects.

    PubMed

    Maller, Jerome J; Thomson, Richard H; Ng, Amanda; Mann, Collette; Eager, Michael; Ackland, Helen; Fitzgerald, Paul B; Egan, Gary; Rosenfeld, Jeffrey V

    2016-11-01

    Previous neuroimaging studies have demonstrated structural brain alterations in blind subjects, but most have focused on primary open angle glaucoma or retinopathy of prematurity, used low-field scanners, a limited number of receive channels, or have presented uncorrected results. We recruited 10 blind and 10 age and sex-matched controls to undergo high-resolution MRI using a 3T scanner and a 32-channel receive coil. We evaluated whole-brain morphological differences between the groups as well as manual segmentation of regional hippocampal volumes. There were no hippocampal volume differences between the groups. Whole-brain morphometry showed white matter volume differences between blind and sighted groups including localised larger regions in the visual cortex (occipital gyral volume and thickness) among those with blindness early in life compared to those with blindness later in life. Hence, in our patients, blindness resulted in brain volumetric differences that depend upon duration of blindness. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Watch Me Grow! A Text for the Early Education of the Blind Child = Miradme! Texto para la Educacion Precoz del Nino Ciego.

    ERIC Educational Resources Information Center

    Blind Children's Fund, Aburndale, MA.

    This text assists parents and other caregivers in stimulating the young child with a severe visual impairment, in order to encourage development of normal behaviors which blindness delays and to prevent the appearance of psychological disturbances. Simple language and illustrations describe the stages of child development from newborn to 3 years…

  10. Multiple Polyploidization Events across Asteraceae with Two Nested Events in the Early History Revealed by Nuclear Phylogenomics

    PubMed Central

    Huang, Chien-Hsun; Zhang, Caifei; Liu, Mian; Hu, Yi; Gao, Tiangang; Qi, Ji; Ma, Hong

    2016-01-01

    Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae–Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity. PMID:27604225

  11. Visible induced luminescence reveals invisible rays shining from Christ in the early Christian wall painting of the Transfiguration in Shivta

    PubMed Central

    Tepper, Yotam; Bar-Oz, Guy

    2017-01-01

    The Transfiguration scene depicted in a Byzantine church at Shivta, Israel, is one of two figurative examples of the scene from the early Christian period. The use of Egyptian blue pigment in the wall painting was investigated with various analytical methods. Visible Induced Luminescence (VIL) imaging was used in-situ in order to map the distribution of the Egyptian blue pigment in the painting. The VIL imaging revealed surprising insights into the understanding of the iconography and the technology of this rare painting. Previously undetected elements of the painting include rays of light that were discovered emerging from the body of Christ and illuminating the other figures in the painting. Although this motif is an important part of the Transfiguration narrative and appears in most of its scenes depicted elsewhere, it had not been previously identified in this painting as it was undetectable by any other inspection technique. Another important result is the identification of Egyptian blue as a common blue pigment used at Shivta during the Byzantine period, when it is considered to be very rare. PMID:28949982

  12. Sulfur Geochemistry of a Lacustrine Record from Taiwan Reveals Enhanced Marine Aerosol Input during the Early Holocene

    PubMed Central

    Ding, Xiaodong; Li, Dawei; Zheng, Liwei; Bao, Hongyan; Chen, Huei-Fen; Kao, Shuh-Ji

    2016-01-01

    Lacustrine record of marine aerosol input has rarely been documented. Here, we present the sulfur geochemistry during the last deglaciation and early Holocene of a sediment core retrieved from the Dongyuan Lake in southern Taiwan. An unusually high sulfur peak accompanying pyrite presence is observed at 10.5 ka BP. Such high sulfur content in lacustrine record is unusual. The δ34S of sulfur varied from +9.5 to + 17.1‰ with two significant positive shifts at 10.5 and 9.4 ka BP. The sources of sulfur and potential processes involving the sulfur isotope variation including bacterial sulfate reduction, volcanic emissions, in-catchment sulfide oxidation and marine aerosol input are discussed. Enhanced marine aerosol input is the most likely explanation for such sulfur peaks and δ34S shifts. The positive δ34S shifts appeared concurrently with the maximum landslide events over Taiwan resulted from enhanced typhoon activities. The synchronicity among records suggests that increased typhoon activities promoted sea spray, and consequently enhanced the marine aerosol input with 34S-enriched sulfate. Our sulfur geochemistry data revealed sea spray history and marine influence onto terrestrial environment at coastal regions. Wider coverage of spatial-temporal lacustrine sulfur geochemistry record is needed to validate the applicability of sulfur proxy in paleoenvironmental research. PMID:27941864

  13. Visible induced luminescence reveals invisible rays shining from Christ in the early Christian wall painting of the Transfiguration in Shivta.

    PubMed

    Linn, Ravit; Tepper, Yotam; Bar-Oz, Guy

    2017-01-01

    The Transfiguration scene depicted in a Byzantine church at Shivta, Israel, is one of two figurative examples of the scene from the early Christian period. The use of Egyptian blue pigment in the wall painting was investigated with various analytical methods. Visible Induced Luminescence (VIL) imaging was used in-situ in order to map the distribution of the Egyptian blue pigment in the painting. The VIL imaging revealed surprising insights into the understanding of the iconography and the technology of this rare painting. Previously undetected elements of the painting include rays of light that were discovered emerging from the body of Christ and illuminating the other figures in the painting. Although this motif is an important part of the Transfiguration narrative and appears in most of its scenes depicted elsewhere, it had not been previously identified in this painting as it was undetectable by any other inspection technique. Another important result is the identification of Egyptian blue as a common blue pigment used at Shivta during the Byzantine period, when it is considered to be very rare.

  14. Epigenomic profiling of men exposed to early-life stress reveals DNA methylation differences in association with current mental state.

    PubMed

    Khulan, B; Manning, J R; Dunbar, D R; Seckl, J R; Raikkonen, K; Eriksson, J G; Drake, A J

    2014-09-23

    Early-life stress (ELS) is known to be associated with an increased risk of neuropsychiatric and cardiometabolic disease in later life. One of the potential mechanisms underpinning this is through effects on the epigenome, particularly changes in DNA methylation. Using a well-phenotyped cohort of 83 men from the Helsinki Birth Cohort Study, who experienced ELS in the form of separation from their parents during childhood, and a group of 83 matched controls, we performed a genome-wide analysis of DNA methylation in peripheral blood. We found no differences in DNA methylation between men who were separated from their families and non-separated men; however, we did identify differences in DNA methylation in association with the development of at least mild depressive symptoms over the subsequent 5-10 years. Notably, hypomethylation was identified at a number of genes with roles in brain development and/or function in association with depressive symptoms. Pathway analysis revealed an enrichment of DNA methylation changes in pathways associated with development and morphogenesis, DNA and transcription factor binding and programmed cell death. Our results support the concept that DNA methylation differences may be important in the pathogenesis of psychiatric disease.

  15. Novel genes involved in severe early-onset obesity revealed by rare copy number and sequence variants.

    PubMed

    Serra-Juhé, Clara; Martos-Moreno, Gabriel Á; Bou de Pieri, Francesc; Flores, Raquel; González, Juan R; Rodríguez-Santiago, Benjamín; Argente, Jesús; Pérez-Jurado, Luis A

    2017-05-01

    Obesity is a multifactorial disorder with high heritability (50-75%), which is probably higher in early-onset and severe cases. Although rare monogenic forms and several genes and regions of susceptibility, including copy number variants (CNVs), have been described, the genetic causes underlying the disease still remain largely unknown. We searched for rare CNVs (>100kb in size, altering genes and present in <1/2000 population controls) in 157 Spanish children with non-syndromic early-onset obesity (EOO: body mass index >3 standard deviations above the mean at <3 years of age) using SNP array molecular karyotypes. We then performed case control studies (480 EOO cases/480 non-obese controls) with the validated CNVs and rare sequence variants (RSVs) detected by targeted resequencing of selected CNV genes (n = 14), and also studied the inheritance patterns in available first-degree relatives. A higher burden of gain-type CNVs was detected in EOO cases versus controls (OR = 1.71, p-value = 0.0358). In addition to a gain of the NPY gene in a familial case with EOO and attention deficit hyperactivity disorder, likely pathogenic CNVs included gains of glutamate receptors (GRIK1, GRM7) and the X-linked gastrin-peptide receptor (GRPR), all inherited from obese parents. Putatively functional RSVs absent in controls were also identified in EOO cases at NPY, GRIK1 and GRPR. A patient with a heterozygous deletion disrupting two contiguous and related genes, SLCO4C1 and SLCO6A1, also had a missense RSV at SLCO4C1 on the other allele, suggestive of a recessive model. The genes identified showed a clear enrichment of shared co-expression partners with known genes strongly related to obesity, reinforcing their role in the pathophysiology of the disease. Our data reveal a higher burden of rare CNVs and RSVs in several related genes in patients with EOO compared to controls, and implicate NPY, GRPR, two glutamate receptors and SLCO4C1 in highly penetrant forms of familial obesity.

  16. Novel genes involved in severe early-onset obesity revealed by rare copy number and sequence variants

    PubMed Central

    Flores, Raquel; González, Juan R.; Argente, Jesús; Pérez-Jurado, Luis A.

    2017-01-01

    Obesity is a multifactorial disorder with high heritability (50–75%), which is probably higher in early-onset and severe cases. Although rare monogenic forms and several genes and regions of susceptibility, including copy number variants (CNVs), have been described, the genetic causes underlying the disease still remain largely unknown. We searched for rare CNVs (>100kb in size, altering genes and present in <1/2000 population controls) in 157 Spanish children with non-syndromic early-onset obesity (EOO: body mass index >3 standard deviations above the mean at <3 years of age) using SNP array molecular karyotypes. We then performed case control studies (480 EOO cases/480 non-obese controls) with the validated CNVs and rare sequence variants (RSVs) detected by targeted resequencing of selected CNV genes (n = 14), and also studied the inheritance patterns in available first-degree relatives. A higher burden of gain-type CNVs was detected in EOO cases versus controls (OR = 1.71, p-value = 0.0358). In addition to a gain of the NPY gene in a familial case with EOO and attention deficit hyperactivity disorder, likely pathogenic CNVs included gains of glutamate receptors (GRIK1, GRM7) and the X-linked gastrin-peptide receptor (GRPR), all inherited from obese parents. Putatively functional RSVs absent in controls were also identified in EOO cases at NPY, GRIK1 and GRPR. A patient with a heterozygous deletion disrupting two contiguous and related genes, SLCO4C1 and SLCO6A1, also had a missense RSV at SLCO4C1 on the other allele, suggestive of a recessive model. The genes identified showed a clear enrichment of shared co-expression partners with known genes strongly related to obesity, reinforcing their role in the pathophysiology of the disease. Our data reveal a higher burden of rare CNVs and RSVs in several related genes in patients with EOO compared to controls, and implicate NPY, GRPR, two glutamate receptors and SLCO4C1 in highly penetrant forms of familial obesity

  17. The complete mitochondrial genome of Pauropus longiramus (Myriapoda: Pauropoda): implications on early diversification of the myriapods revealed from comparative analysis.

    PubMed

    Dong, Yan; Sun, Hongying; Guo, Hua; Pan, Da; Qian, Changyuan; Hao, Sijing; Zhou, Kaiya

    2012-08-15

    Myriapods are among the earliest arthropods and may have evolved to become part of the terrestrial biota more than 400 million years ago. A noticeable lack of mitochondrial genome data from Pauropoda hampers phylogenetic and evolutionary studies within the subphylum Myriapoda. We sequenced the first complete mitochondrial genome of a microscopic pauropod, Pauropus longiramus (Arthropoda: Myriapoda), and conducted comprehensive mitogenomic analyses across the Myriapoda. The pauropod mitochondrial genome is a circular molecule of 14,487 bp long and contains the entire set of thirty-seven genes. Frequent intergenic overlaps occurred between adjacent tRNAs, and between tRNA and protein-coding genes. This is the first example of a mitochondrial genome with multiple intergenic overlaps and reveals a strategy for arthropods to effectively compact the mitochondrial genome by overlapping and truncating tRNA genes with neighbor genes, instead of only truncating tRNAs. Phylogenetic analyses based on protein-coding genes provide strong evidence that the sister group of Pauropoda is Symphyla. Additionally, approximately unbiased (AU) tests strongly support the Progoneata and confirm the basal position of Chilopoda in Myriapoda. This study provides an estimation of myriapod origins around 555 Ma (95% CI: 444-704 Ma) and this date is comparable with that of the Cambrian explosion and candidate myriapod-like fossils. A new time-scale suggests that deep radiations during early myriapod diversification occurred at least three times, not once as previously proposed. A Carboniferous origin of pauropods is congruent with the idea that these taxa are derived, rather than basal, progoneatans. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Multiple Polyploidization Events across Asteraceae with Two Nested Events in the Early History Revealed by Nuclear Phylogenomics.

    PubMed

    Huang, Chien-Hsun; Zhang, Caifei; Liu, Mian; Hu, Yi; Gao, Tiangang; Qi, Ji; Ma, Hong

    2016-11-01

    Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae-Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  19. Time-resolved dual transcriptomics reveal early induced Nicotiana benthamiana root genes and conserved infection-promoting Phytophthora palmivora effectors.

    PubMed

    Evangelisti, Edouard; Gogleva, Anna; Hainaux, Thomas; Doumane, Mehdi; Tulin, Frej; Quan, Clément; Yunusov, Temur; Floch, Kévin; Schornack, Sebastian

    2017-05-11

    Plant-pathogenic oomycetes are responsible for economically important losses in crops worldwide. Phytophthora palmivora, a tropical relative of the potato late blight pathogen, causes rotting diseases in many tropical crops including papaya, cocoa, oil palm, black pepper, rubber, coconut, durian, mango, cassava and citrus. Transcriptomics have helped to identify repertoires of host-translocated microbial effector proteins which counteract defenses and reprogram the host in support of infection. As such, these studies have helped in understanding how pathogens cause diseases. Despite the importance of P. palmivora diseases, genetic resources to allow for disease resistance breeding and identification of microbial effectors are scarce. We employed the model plant Nicotiana benthamiana to study the P. palmivora root infections at the cellular and molecular levels. Time-resolved dual transcriptomics revealed different pathogen and host transcriptome dynamics. De novo assembly of P. palmivora transcriptome and semi-automated prediction and annotation of the secretome enabled robust identification of conserved infection-promoting effectors. We show that one of them, REX3, suppresses plant secretion processes. In a survey for early transcriptionally activated plant genes we identified a N. benthamiana gene specifically induced at infected root tips that encodes a peptide with danger-associated molecular features. These results constitute a major advance in our understanding of P. palmivora diseases and establish extensive resources for P. palmivora pathogenomics, effector-aided resistance breeding and the generation of induced resistance to Phytophthora root infections. Furthermore, our approach to find infection-relevant secreted genes is transferable to other pathogen-host interactions and not restricted to plants.

  20. What Equivocal Data from Single Case Comparison Studies Reveal about Evidence-Based Practices in Early Childhood Special Education

    ERIC Educational Resources Information Center

    Ledford, Jennifer R.; Barton, Erin E.; Hardy, Jessica K.; Elam, Katie; Seabolt, Jordan; Shanks, Meredith; Hemmeter, M. L.; Kaiser, Ann

    2016-01-01

    Although comparison studies are important in early intervention/early childhood special education (EI/ECSE), results of well-designed comparison studies are likely to be unpublished because of undifferentiated or differently differentiated results across participants. The purpose of this article is to highlight the utility of comparison designs in…

  1. Upwelling history of the Mediterranean Sea revealed by stunted growth in the planktic foraminifera Orbulina universa (early Messinian, Crete, Greece)

    NASA Astrophysics Data System (ADS)

    Brachert, T. C.; Bornemann, A.; Reuter, M.; Galer, S. J.; Grimm, K. I.; Fassoulas, C.

    2015-01-01

    Microfossil and stable isotope data (δ13C, δ18O) from deep-water sediments of Late Miocene age in the Mediterranean region have revealed a stepwise restriction of the Mediterranean prior to the Messinian Salinity Crisis which was modulated by a cyclicity responding to orbital precession. Very little is known with regard to the effects of these changes on shallow water environments of carbonate platforms and ramps. This work is based on a geological section on Crete (Greece) exposing sediments of early Messinian age, which documents the coeval response of pelagic and neritic systems to oceanographic changes. We discuss a dataset of planktic and benthic foraminifera assemblages in conjunction with size measurements ( n = 6,777) and isotope analyses (δ18O, δ13C) of the planktic foraminifera Orbulina universa with regard to reef growth patterns. The planktic foraminifera fauna displays pronounced cyclical abundance changes of warm, oligotrophic ( O. universa) and cold, meso- to eu-trophic taxa (globigerinids, neogloboquadrinids). This cyclicity corresponds to lithological changes from laminated to homogeneous marls on the precessional frequency band. In beds rich in mesotrophic foraminifera, O. universa is rare and the test is ~50 % smaller than average. Growth and size of O. universa is affected by various environmental factors, including temperature, trophic resources, illumination and O2 content of ambient water. Explaining size variability by water temperature implies a change of ~11 °C over one precessional cycle. This estimate is in disagreement with growth patterns and stable isotope data of displaced reef corals ( Porites, Tarbellastraea) documenting almost constant sea-surface temperatures, but substantial evaporation. Therefore, moderate temperature changes in a context of intense evaporation (high salinity) and water column destabilization associated with upward mixing of colder water masses with higher nutrient concentrations and low O2 content better

  2. Exome Sequencing Analysis Reveals Variants in Primary Immunodeficiency Genes in Patients With Very Early Onset Inflammatory Bowel Disease

    PubMed Central

    Kelsen, Judith R.; Dawany, Noor; Moran, Christopher J.; Petersen, Britt-Sabina; Sarmady, Mahdi; Sasson, Ariella; Pauly-Hubbard, Helen; Martinez, Alejandro; Maurer, Kelly; Soong, Joanne; Rappaport, Eric; Franke, Andre; Keller, Andreas; Winter, Harland S.; Mamula, Petar; Piccoli, David; Artis, David; Sonnenberg, Gregory F.; Daly, Mark; Sullivan, Kathleen E.; Baldassano, Robert N.; Devoto, Marcella

    2016-01-01

    Background & Aims Very early onset inflammatory bowel disease (VEO-IBD), IBD diagnosed ≤5 y of age, frequently presents with a different and more severe phenotype than older-onset IBD. We investigated whether patients with VEO-IBD carry rare or novel variants in genes associated with immunodeficiencies that might contribute to disease development. Methods Patients with VEO-IBD and parents (when available) were recruited from the Children's Hospital of Philadelphia from March 2013 through July 2014. We analyzed DNA from 125 patients with VEO-IBD (ages 3 weeks to 4 y) and 19 parents, 4 of whom also had IBD. Exome capture was performed by Agilent SureSelect V4, and sequencing was performed using the Illumina HiSeq platform. Alignment to human genome GRCh37 was achieved followed by post-processing and variant calling. Following functional annotation, candidate variants were analyzed for change in protein function, minor allele frequency <0.1%, and scaled combined annotation dependent depletion scores ≤10. We focused on genes associated with primary immunodeficiencies and related pathways. An additional 210 exome samples from patients with pediatric IBD (n=45) or adult-onset Crohn's disease (n=20) and healthy individuals (controls, n=145) were obtained from the University of Kiel, Germany and used as control groups. Results Four-hundred genes and regions associated with primary immunodeficiency, covering approximately 6500 coding exons totaling > 1 Mbp of coding sequence, were selected from the whole exome data. Our analysis revealed novel and rare variants within these genes that could contribute to the development of VEO-IBD, including rare heterozygous missense variants in IL10RA and previously unidentified variants in MSH5 and CD19. Conclusions In an exome sequence analysis of patients with VEO-IBD and their parents, we identified variants in genes that regulate B- and T-cell functions and could contribute to pathogenesis. Our analysis could lead to the

  3. Social recovery therapy in combination with early intervention services for enhancement of social recovery in patients with first-episode psychosis (SUPEREDEN3): a single-blind, randomised controlled trial.

    PubMed

    Fowler, David; Hodgekins, Jo; French, Paul; Marshall, Max; Freemantle, Nick; McCrone, Paul; Everard, Linda; Lavis, Anna; Jones, Peter B; Amos, Tim; Singh, Swaran; Sharma, Vimal; Birchwood, Max

    2018-01-01

    Provision of early intervention services has increased the rate of social recovery in patients with first-episode psychosis; however, many individuals have continuing severe and persistent problems with social functioning. We aimed to assess the efficacy of early intervention services augmented with social recovery therapy in patients with first-episode psychosis. The primary hypothesis was that social recovery therapy plus early intervention services would lead to improvements in social recovery. We did this single-blind, phase 2, randomised controlled trial (SUPEREDEN3) at four specialist early intervention services in the UK. We included participants who were aged 16-35 years, had non-affective psychosis, had been clients of early intervention services for 12-30 months, and had persistent and severe social disability, defined as engagement in less than 30 h per week of structured activity. Participants were randomly assigned (1:1), via computer-generated randomisation with permuted blocks (sizes of four to six), to receive social recovery therapy plus early intervention services or early intervention services alone. Randomisation was stratified by sex and recruitment centre (Norfolk, Birmingham, Lancashire, and Sussex). By necessity, participants were not masked to group allocation, but allocation was concealed from outcome assessors. The primary outcome was time spent in structured activity at 9 months, as measured by the Time Use Survey. Analysis was by intention to treat. This trial is registered with ISRCTN, number ISRCTN61621571. Between Oct 1, 2012, and June 20, 2014, we randomly assigned 155 participants to receive social recovery therapy plus early intervention services (n=76) or early intervention services alone (n=79); the intention-to-treat population comprised 154 patients. At 9 months, 143 (93%) participants had data for the primary outcome. Social recovery therapy plus early intervention services was associated with an increase in structured

  4. Synchrotron FTIR microspectroscopy reveals early adipogenic differentiation of human mesenchymal stem cells at single-cell level

    SciTech Connect

    Liu, Zhixiao; University of Chinese Academy of Science, Beijing 100049; Tang, Yuzhao

    Human mesenchymal stem cells (hMSCs) have been used as an ideal in vitro model to study human adipogenesis. However, little knowledge of the early stage differentiation greatly hinders our understanding on the mechanism of the adipogenesis processes. In this study, synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy was applied to track the global structural and compositional changes of lipids, proteins and nucleic acids inside individual hMSCs along the time course. The multivariate analysis of the SR-FTIR spectra distinguished the dynamic and significant changes of the lipids and nucleic acid at early differentiation stage. Importantly, changes of lipid structure during early daysmore » (Day 1–3) of differentiation might serve as a potential biomarker in identifying the state in early differentiation at single cell level. These results proved that SR-FTIR is a powerful tool to study the stem cell fate determination and early lipogenesis events. - Highlights: • Molecular events occur in the early adipogenic differentiation stage of hMSCs are studied by SR-FTIR. • SR-FTIR data suggest that lipids may play an important role in hMSCs determination. • As potential biomarkers, lipids peaks can identify the state of cell in early differentiation stage at single-cell level.« less

  5. A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

    PubMed

    Stevens, R B; Wrenshall, L E; Miles, C D; Farney, A C; Jie, T; Sandoz, J P; Rigley, T H; Osama Gaber, A

    2016-06-01

    A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.). © Copyright 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of the American Society of Transplantation and the American Society of Transplant Surgeons.

  6. Diabetic Retinopathy Screening and Monitoring of Early Stage Disease in Australian General Practice: Tackling Preventable Blindness within a Chronic Care Model.

    PubMed

    Crossland, Lisa; Askew, Deborah; Ware, Robert; Cranstoun, Peter; Mitchell, Paul; Bryett, Andrew; Jackson, Claire

    2016-01-01

    Diabetic retinopathy (DR) is the leading cause of preventable blindness in Australia. Up to 50% of people with proliferative DR who do not receive timely treatment will become legally blind within five years. Innovative and accessible screening, involving a variety of primary care providers, will become increasingly important if patients with diabetes are to receive optimal eye care. An open controlled trial design was used. Five intervention practices in urban, regional, and rural Australia partnered with ophthalmologists via telehealth undertook DR screening and monitoring of type 2 diabetes patients and were compared with control practices undertaking usual care 2011-2014. Recorded screening rates were 100% across intervention practices, compared with 22-53% in control practices. 31/577 (5%) of patients in the control practices were diagnosed with mild-moderate DR, of whom 9 (29%) had appropriate follow-up recorded. This was compared with 39/447 (9%) of patients in the intervention group, of whom 37 (95%) had appropriate follow-up recorded. General practice-based DR screening via Annual Cycle of Care arrangements is effective across differing practice locations. It offers improved recording of screening outcomes for Australians with type 2 diabetes and better follow-up of those with screen abnormalities.

  7. Enhanced tactile encoding and memory recognition in congenital blindness.

    PubMed

    D'Angiulli, Amedeo; Waraich, Paul

    2002-06-01

    Several behavioural studies have shown that early-blind persons possess superior tactile skills. Since neurophysiological data show that early-blind persons recruit visual as well as somatosensory cortex to carry out tactile processing (cross-modal plasticity), blind persons' sharper tactile skills may be related to cortical re-organisation resulting from loss of vision early in their life. To examine the nature of blind individuals' tactile superiority and its implications for cross-modal plasticity, we compared the tactile performance of congenitally totally blind, low-vision and sighted children on raised-line picture identification test and re-test, assessing effects of task familiarity, exploratory strategy and memory recognition. What distinguished the blind from the other children was higher memory recognition and higher tactile encoding associated with efficient exploration. These results suggest that enhanced perceptual encoding and recognition memory may be two cognitive correlates of cross-modal plasticity in congenital blindness.

  8. Blindness enhances tactile acuity and haptic 3-D shape discrimination.

    PubMed

    Norman, J Farley; Bartholomew, Ashley N

    2011-10-01

    This study compared the sensory and perceptual abilities of the blind and sighted. The 32 participants were required to perform two tasks: tactile grating orientation discrimination (to determine tactile acuity) and haptic three-dimensional (3-D) shape discrimination. The results indicated that the blind outperformed their sighted counterparts (individually matched for both age and sex) on both tactile tasks. The improvements in tactile acuity that accompanied blindness occurred for all blind groups (congenital, early, and late). However, the improvements in haptic 3-D shape discrimination only occurred for the early-onset and late-onset blindness groups; the performance of the congenitally blind was no better than that of the sighted controls. The results of the present study demonstrate that blindness does lead to an enhancement of tactile abilities, but they also suggest that early visual experience may play a role in facilitating haptic 3-D shape discrimination.

  9. [Blindness: Three Papers.

    ERIC Educational Resources Information Center

    Jernigan, Kenneth

    Three papers by the president of the National Federation of the Blind are presented. The first, "A Definition of Blindness," examines definitions of blindness, asserting the advantages of a functional or sociological definition over a physical or medical definition. He cites harm in legal distinctions between partial and full blindness and between…

  10. Multimodal Swallowing Evaluation with High-Resolution Manometry Reveals Subtle Swallowing Changes in Early and Mid-Stage Parkinson Disease.

    PubMed

    Jones, Corinne A; Ciucci, Michelle R

    2016-01-01

    Parkinson disease (PD) has detrimental effects on swallowing function. Treatment options are largely behavioral; thus, patients would benefit from an earlier start to therapy. Early swallowing changes in PD are not well-known, so patients do not typically receive swallowing treatment until later in the progression of PD. We used predictive modeling to determine what quantitative swallowing variables best differentiate individuals with early to mid-stage PD from healthy controls. Participants included twenty-six individuals with early to mid-stage PD and 26 healthy, age- and sex-matched controls. Swallowing was evaluated by simultaneous high-resolution manometry and videofluoroscopy as well as the Sydney Swallow Questionnaire (SSQ). Binomial logistic regression was performed on 4 sets of data: 1) high-resolution manometry only; 2) videofluoroscopy only; 3) SSQ only; and 4) all data combined. A model from a combined data set had the highest accuracy in differentiating individuals with PD from controls. The model included maximum pressure in the velopharynx (soft palate), pressure variability in the velopharynx, and the SSQ item concerning difficulty with swallowing saliva. No significant models could be generated using the videofluoroscopy data. Individuals with PD show quantitative changes in pressure generation and are able to self-assess aspects of swallowing function in the early and mid-stages of PD, even in the absence of swallowing changes seen on videofluoroscopy. A multimodal approach for the assessment of swallowing may be more accurate for determining subtle swallowing changes that occur in the early stages of PD.

  11. Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold

    PubMed Central

    2010-01-01

    Background The common cold, the most prevalent contagious viral disease in humans still lacks a safe and effective antiviral treatment. Iota-Carrageenan is broadly active against respiratory viruses in-vitro and has an excellent safety profile. This study investigated the efficacy and safety of an Iota-Carrageenan nasal spray in patients with common cold symptoms. Methods In a randomized, double-blind, placebo-controlled exploratory trial, 35 human subjects suffering from early symptoms of common cold received Iota-Carrageenan (0.12%) in a saline solution three times daily for 4 days, compared to placebo. Results Administration of Iota-Carrageenan nasal spray reduced the symptoms of common cold (p = 0.046) and the viral load in nasal lavages (p = 0.009) in patients with early symptoms of common cold. Pro-inflammatory mediators FGF-2, Fractalkine, GRO, G-CSF, IL-8, IL-1α, IP-10, IL-10, and IFN-α2 were reduced in the Iota-Carrageenan group. Conclusions Iota-Carrageenan nasal spray appears to be a promising treatment for safe and effective treatment of early symptoms of common cold. Larger trials are indicated to confirm the results. PMID:20696083

  12. Safety and Efficacy of the ACE-Inhibitor Ramipril in Alport Syndrome: The Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase III EARLY PRO-TECT Alport Trial in Pediatric Patients.

    PubMed

    Gross, Oliver; Friede, Tim; Hilgers, Reinhard; Görlitz, Anke; Gavénis, Karsten; Ahmed, Raees; Dürr, Ulrike

    2012-01-01

    Introduction. Retrospective observational data show that ACE-inhibitor therapy delays renal failure and improves life expectancy in Alport patients with proteinuria. The EARLY PRO-TECT Alport trial assesses the safety and efficacy of early therapy onset with ramipril in pediatric Alport patients. Methods and analysis. This double-blind, randomized, placebo-controlled, multicenter phase III trial (NCT01485978; EudraCT-number 2010-024300-10) includes 120 pediatric patients aged 24 months to 18 years with early stages of Alport syndrome (isolated hematuria or microalbuminuria). From March 2012, up to 80 patients will be randomized 1:1 to ramipril or placebo. In the event of disease progression during 3-year treatment, patients are unblinded and ramipril is initiated, if applicable. Approximately 40 patients receive open-label ramipril contributing to the safety database. Primary end-points are "time to progression to next disease level" and "incidence of adverse drug events before disease progression." Treatment effect estimates from the randomized comparison and Alport registry data will be combined in supportive analyses to maximize evidence. Conclusion. Without this trial, ACE inhibitors may become standard off-label treatment in Alport syndrome without satisfactory evidence base. The results are expected to be of relevance for therapy of all pediatric patients with kidney disease, and the trial protocol might serve as a model for other rare pediatric glomerulopathies.

  13. Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold.

    PubMed

    Eccles, Ron; Meier, Christiane; Jawad, Martez; Weinmüllner, Regina; Grassauer, Andreas; Prieschl-Grassauer, Eva

    2010-08-10

    The common cold, the most prevalent contagious viral disease in humans still lacks a safe and effective antiviral treatment. Iota-Carrageenan is broadly active against respiratory viruses in-vitro and has an excellent safety profile. This study investigated the efficacy and safety of an Iota-Carrageenan nasal spray in patients with common cold symptoms. In a randomized, double-blind, placebo-controlled exploratory trial, 35 human subjects suffering from early symptoms of common cold received Iota-Carrageenan (0.12%) in a saline solution three times daily for 4 days, compared to placebo. Administration of Iota-Carrageenan nasal spray reduced the symptoms of common cold (p = 0.046) and the viral load in nasal lavages (p = 0.009) in patients with early symptoms of common cold. Pro-inflammatory mediators FGF-2, Fractalkine, GRO, G-CSF, IL-8, IL-1alpha, IP-10, IL-10, and IFN-alpha2 were reduced in the Iota-Carrageenan group. Iota-Carrageenan nasal spray appears to be a promising treatment for safe and effective treatment of early symptoms of common cold. Larger trials are indicated to confirm the results.

  14. Multimodal swallowing evaluation with high-resolution manometry reveals subtle swallowing changes in early and mid-stage Parkinson disease

    PubMed Central

    Jones, Corinne A; Ciucci, Michelle R

    2015-01-01

    Background Parkinson disease (PD) has detrimental effects on swallowing function. Treatment options are largely behavioral; thus, patients would benefit from an earlier start to therapy. Early swallowing changes in PD are not well-known, so patients do not typically receive swallowing treatment until later in the progression of PD. Objective We used predictive modeling to determine what quantitative swallowing variables best differentiate individuals with early to mid-stage PD from healthy controls. Methods Participants included twenty-six individuals with early to mid-stage PD and 26 healthy, age- and sex-matched controls. Swallowing was evaluated by simultaneous high-resolution manometry and videofluoroscopy as well as the Sydney Swallow Questionnaire (SSQ). Binomial logistic regression was performed on 4 sets of data: 1) high-resolution manometry only; 2) videofluoroscopy only; 3) SSQ only; and 4) all data combined. Results A model from a combined data set had the highest accuracy in differentiating individuals with PD from controls. The model included maximum pressure in the velopharynx (soft palate), pressure variability in the velopharynx, and the SSQ item concerning difficulty with saliva swallowing. No significant models could be generated using the videofluoroscopy data. Conclusions Individuals with PD show quantitative changes in pressure generation and are able to self-assess aspects of swallowing function in the early and mid-stages of PD, even in the absence of swallowing changes seen on videofluoroscopy. A multimodal approach for the assessment of swallowing may be more accurate for determining subtle swallowing changes that occur in the early stages of PD. PMID:26891176

  15. Research: Treatment Study to determine the durability of glycaemic control with early treatment with a vildagliptin–metformin combination regimen vs. standard-of-care metformin monotherapy—the VERIFY trial: a randomized double-blind trial

    PubMed Central

    Del Prato, S; Foley, J E; Kothny, W; Kozlovski, P; Stumvoll, M; Paldánius, P M; Matthews, D R

    2014-01-01

    Aims Durability of good glycaemic control (HbA1c) is of importance as it can be the foundation for delaying diabetic complications. It has been hypothesized that early initiation of treatment with the combination of oral anti-diabetes agents with complementary mechanisms of action can increase the durability of glycaemic control compared with metformin monotherapy followed by a stepwise addition of oral agents. Dipeptidyl peptidase-4 inhibitors are good candidates for early use as they are efficacious in combination with metformin, show weight neutrality and a low risk of hypoglycaemia. We aimed to test the hypothesis that early combined treatment of metformin and vildagliptin slows β-cell deterioration as measured by HbA1c. Methods Approximately 2000 people with Type 2 diabetes mellitus who were drug-naive or who were treated with metformin for less than 1 month, and who have HbA1c of 48–58 mmol/mol (6.5–7.5%), will be randomized in a 1:1 ratio in VERIFY, a 5-year multinational, double-blind, parallel-group study designed to compare early initiation of a vildagliptin–metformin combination with standard-of-care initiation of metformin monotherapy, followed by the stepwise addition of vildagliptin when glycaemia deteriorates. Further deterioration will be treated with insulin. The primary analysis for treatment failure will be from a Cox proportional hazard regression model and the durability of glycaemic control will be evaluated by assessing treatment failure rate and the rate of loss in glycaemic control over time as co-primary endpoints. Summary VERIFY is the first study to investigate the long-term clinical benefits of early combination treatment vs. the standard-of-care metformin monotherapy with a second agent added by threshold criteria. PMID:24863949

  16. Gene expression profiling reveals underlying molecular mechanisms of the early stages of tamoxifen-induced rat hepatocarcinogenesis

    SciTech Connect

    Pogribny, Igor P.; Bagnyukova, Tetyana V.; Tryndyak, Volodymyr P.

    2007-11-15

    Tamoxifen is a widely used anti-estrogenic drug for chemotherapy and, more recently, for the chemoprevention of breast cancer. Despite the indisputable benefits of tamoxifen in preventing the occurrence and re-occurrence of breast cancer, the use of tamoxifen has been shown to induce non-alcoholic steatohepatitis, which is a life-threatening fatty liver disease with a risk of progression to cirrhosis and hepatocellular carcinoma. In recent years, the high-throughput microarray technology for large-scale analysis of gene expression has become a powerful tool for increasing the understanding of the molecular mechanisms of carcinogenesis and for identifying new biomarkers with diagnostic and predictive values. Inmore » the present study, we used the high-throughput microarray technology to determine the gene expression profiles in the liver during early stages of tamoxifen-induced rat hepatocarcinogenesis. Female Fisher 344 rats were fed a 420 ppm tamoxifen containing diet for 12 or 24 weeks, and gene expression profiles were determined in liver of control and tamoxifen-exposed rats. The results indicate that early stages of tamoxifen-induced liver carcinogenesis are characterized by alterations in several major cellular pathways, specifically those involved in the tamoxifen metabolism, lipid metabolism, cell cycle signaling, and apoptosis/cell proliferation control. One of the most prominent changes during early stages of tamoxifen-induced hepatocarcinogenesis is dysregulation of signaling pathways in cell cycle progression from the G{sub 1} to S phase, evidenced by the progressive and sustained increase in expression of the Pdgfc, Calb3, Ets1, and Ccnd1 genes accompanied by the elevated level of the PI3K, p-PI3K, Akt1/2, Akt3, and cyclin B, D1, and D3 proteins. The early appearance of these alterations suggests their importance in the mechanism of neoplastic cell transformation induced by tamoxifen.« less

  17. Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever

    PubMed Central

    Thein, Tun Linn; Fang, Jinling; Pang, Junxiong; Ooi, Eng Eong; Leo, Yee Sin; Ong, Choon Nam; Tannenbaum, Steven R.

    2016-01-01

    Effective triage of dengue patients early in the disease course for in- or out-patient management would be useful for optimal healthcare resource utilization while minimizing poor clinical outcome due to delayed intervention. Yet, early prognosis of severe dengue is hampered by the heterogeneity in clinical presentation and routine hematological and biochemical measurements in dengue patients that collectively correlates poorly with eventual clinical outcome. Herein, untargeted liquid-chromatography mass spectrometry metabolomics of serum from patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) in the febrile phase (<96 h) was used to globally probe the serum metabolome to uncover early prognostic biomarkers of DHF. We identified 20 metabolites that are differentially enriched (p<0.05, fold change >1.5) in the serum, among which are two products of tryptophan metabolism–serotonin and kynurenine. Serotonin, involved in platelet aggregation and activation decreased significantly, whereas kynurenine, an immunomodulator, increased significantly in patients with DHF, consistent with thrombocytopenia and immunopathology in severe dengue. To sensitively and accurately evaluate serotonin levels as prognostic biomarkers, we implemented stable-isotope dilution mass spectrometry and used convalescence samples as their own controls. DHF serotonin was significantly 1.98 fold lower in febrile compared to convalescence phase, and significantly 1.76 fold lower compared to DF in the febrile phase of illness. Thus, serotonin alone provided good prognostic utility (Area Under Curve, AUC of serotonin = 0.8). Additionally, immune mediators associated with DHF may further increase the predictive ability than just serotonin alone. Nine cytokines, including IFN-γ, IL-1β, IL-4, IL-8, G-CSF, MIP-1β, FGF basic, TNFα and RANTES were significantly different between DF and DHF, among which IFN-γ ranked top by multivariate statistics. Combining serotonin and IFN-γ improved

  18. A mouse model for creatine transporter deficiency reveals early onset cognitive impairment and neuropathology associated with brain aging.

    PubMed

    Baroncelli, Laura; Molinaro, Angelo; Cacciante, Francesco; Alessandrì, Maria Grazia; Napoli, Debora; Putignano, Elena; Tola, Jonida; Leuzzi, Vincenzo; Cioni, Giovanni; Pizzorusso, Tommaso

    2016-10-01

    Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and autistic-like behavioural disturbances, language and speech impairment. Since no data are available about the neural and molecular underpinnings of this disease, we performed a longitudinal analysis of behavioural and pathological alterations associated with CrT deficiency in a CCDS1 mouse model. We found precocious cognitive and autistic-like defects, mimicking the early key features of human CCDS1. Moreover, mutant mice displayed a progressive impairment of short and long-term declarative memory denoting an early brain aging. Pathological examination showed a prominent loss of GABAergic synapses, marked activation of microglia, reduction of hippocampal neurogenesis and the accumulation of autofluorescent lipofuscin. Our data suggest that brain Cr depletion causes both early intellectual disability and late progressive cognitive decline, and identify novel targets to design intervention strategies aimed at overcoming brain CCDS1 alterations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Representing vision and blindness.

    PubMed

    Ray, Patrick L; Cox, Alexander P; Jensen, Mark; Allen, Travis; Duncan, William; Diehl, Alexander D

    2016-01-01

    There have been relatively few attempts to represent vision or blindness ontologically. This is unsurprising as the related phenomena of sight and blindness are difficult to represent ontologically for a variety of reasons. Blindness has escaped ontological capture at least in part because: blindness or the employment of the term 'blindness' seems to vary from context to context, blindness can present in a myriad of types and degrees, and there is no precedent for representing complex phenomena such as blindness. We explore current attempts to represent vision or blindness, and show how these attempts fail at representing subtypes of blindness (viz., color blindness, flash blindness, and inattentional blindness). We examine the results found through a review of current attempts and identify where they have failed. By analyzing our test cases of different types of blindness along with the strengths and weaknesses of previous attempts, we have identified the general features of blindness and vision. We propose an ontological solution to represent vision and blindness, which capitalizes on resources afforded to one who utilizes the Basic Formal Ontology as an upper-level ontology. The solution we propose here involves specifying the trigger conditions of a disposition as well as the processes that realize that disposition. Once these are specified we can characterize vision as a function that is realized by certain (in this case) biological processes under a range of triggering conditions. When the range of conditions under which the processes can be realized are reduced beyond a certain threshold, we are able to say that blindness is present. We characterize vision as a function that is realized as a seeing process and blindness as a reduction in the conditions under which the sight function is realized. This solution is desirable because it leverages current features of a major upper-level ontology, accurately captures the phenomenon of blindness, and can be

  20. Mechanism and early intervention research on ALI during emergence surgery of Stanford type-A AAD: Study protocol for a prospective, double-blind, clinical trial.

    PubMed

    Cheng, Yi; Jin, Mu; Dong, Xiuhua; Sun, Lizhong; Liu, Jing; Wang, Rong; Yang, Yanwei; Lin, Peirong; Hou, Siyu; Ma, Yuehua; Wang, Yuefeng; Pan, Xudong; Lu, Jiakai; Cheng, Weiping

    2016-10-01

    Stanford type-A acute aortic dissection (AAD) is a severe cardiovascular disease demonstrating the characteristics of acute onset and rapid development, with high morbidity and mortality. The available evidence shows that preoperative acute lung injury (ALI) induced by Stanford type-A AAD is a frequent and important cause for a number of untoward consequences. However, there is no study assessing the incidence of preoperative ALI and its independent determinants before Standford type-A AAD surgery in Chinese adult patients. This is a prospective, double-blind, signal-center clinical trial. We will recruit 130 adult patients undergoing Stanford type-A AAD surgery. The incidence of preoperative ALI will be evaluated. Perioperative clinical baselines and serum variables including coagulation, fibrinolysis, inflammatory, reactive oxygen species, and endothelial cell function will be assayed. The independent factors affecting the occurrence of preoperative ALI will be identified by multiple logistic regression analysis. ClinicalTrials.gov (https://register.clinicaltrials.gov/), Registration number NCT01894334.

  1. Immediate versus early loading of two implants placed with a flapless technique supporting mandibular bar-retained overdentures: a single-blinded, randomised controlled clinical trial.

    PubMed

    Cannizzaro, Gioacchino; Leone, Michele; Esposito, Marco

    2008-01-01

    To evaluate the efficacy of immediate loading versus early loading at 6 weeks of bar-retained mandibular overdentures supported by two implants placed with a flapless technique. Sixty patients were randomised: 30 to the immediately loaded group and 30 to the early loaded group. To be immediately loaded, implants had to be inserted with a minimum torque > 48 Ncm. Outcome measures were prosthesis and implant failures, biological and biomechanical complications, patient satisfaction, and Implant Stability Quotient (ISQ) assessed with a resonance frequency analysis instrument. Sixty implants were placed in each group. Flaps had to be raised in nine patients to check drill direction or to better visualise the area after multiple teeth extraction. Two implants in two patients did not reach the planned insertion torque and were immediately replaced by larger diameters ones. After 1 year no drop out occurred and two early loaded implants failed in two patients. There were no statistically significant differences between groups for prosthesis failures, implant losses, complications, and mean ISQ values; however, patients in the immediately loaded group were significantly more satisfied than those loaded early. When comparing mean ISQ values taken 6 weeks after placement with 1-year data within each group, values decreased significantly. Mandibular overdentures can be successfully loaded the same day of implant placement with a minimally invasive surgery, increasing patient satisfaction while decreasing treatment time and patient discomfort. No apparent advantages were seen when loading the overdentures at 6 weeks.

  2. Blind extraction of exoplanetary spectra

    NASA Astrophysics Data System (ADS)

    Morello, Giuseppe; Waldmann, Ingo P.; Tinetti, Giovanna

    2016-06-01

    In the last decade, remote sensing spectroscopy enabled characterization of the atmospheres of extrasolar planets. Transmission and emission spectra of tens of transiting exoplanets have been measured with multiple instruments aboard Spitzer and Hubble Space Telescopes as well as ground-based facilities, revealing the presence of atomic, ionic and molecular species in their atmospheres, and constraining their temperature and pressure profiles.Early analyses were somehow heuristic both in measuring the spectra and in their interpretation, leading to some controversies in the literature.A photometric precision of 0.01% is necessary to detect the atmospheric spectral modulations. Current observatories, except Kepler, were not designed to achieve this precision. Data reduction is necessary to minimize the effect of instrument systematics in order to achieve the target precision. In the past, parametric models have extensively been used by most teams to remove correlated noise with the aid of auxiliary information of the instrument, the so-called optical state vectors (OSVs). Such OSVs can include inter- and intra-pixel position of the star or its spectrum, instrument temperatures and inclinations, and/or other parameters. In some cases, different parameterizations led to discrepant results.We recommend the use of blind non-parametric data detrending techniques to overcome those issues. In particular, we adopt Independent Component Analysis (ICA), i.e. a blind source separation (BSS) technique to disentangle the multiple instrument systematics and astrophysical signals in transit/eclipse light curves. ICA does not require a model for the systematics, and for this reason, it can be applied to any instrument with little changes, if any. ICA-based algorithms have been applied to Spitzer/IRAC and synthetic observations in photometry (Morello et al. 2014, 2015, 2016; Morello 2015) and to Hubble/NICMOS and Spitzer/IRS in spectroscopy (Waldmann 2012, 2014, Waldmann et al. 2013

  3. fMRI-constrained source analysis reveals early top-down modulations of interference processing using a flanker task.

    PubMed

    Siemann, Julia; Herrmann, Manfred; Galashan, Daniela

    2016-08-01

    Usually, incongruent flanker stimuli provoke conflict processing whereas congruent flankers should facilitate task performance. Various behavioral studies reported improved or even absent conflict processing with correctly oriented selective attention. In the present study we attempted to reinvestigate these behavioral effects and to disentangle neuronal activity patterns underlying the attentional cueing effect taking advantage of a combination of the high temporal resolution of Electroencephalographic (EEG) and the spatial resolution of functional magnetic resonance imaging (fMRI). Data from 20 participants were acquired in different sessions per method. We expected the conflict-related N200 event-related potential (ERP) component and areas associated with flanker processing to show validity-specific modulations. Additionally, the spatio-temporal dynamics during cued flanker processing were examined using an fMRI-constrained source analysis approach. In the ERP data we found early differences in flanker processing between validity levels. An early centro-parietal relative positivity for incongruent stimuli occurred only with valid cueing during the N200 time window, while a subsequent fronto-central negativity was specific to invalidly cued interference processing. The source analysis additionally pointed to separate neural generators of these effects. Regional sources in visual areas were involved in conflict processing with valid cueing, while a regional source in the anterior cingulate cortex (ACC) seemed to contribute to the ERP differences with invalid cueing. Moreover, the ACC and precentral gyrus demonstrated an early and a late phase of congruency-related activity differences with invalid cueing. We discuss the first effect to reflect conflict detection and response activation while the latter more likely originated from conflict monitoring and control processes during response competition. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Small RNA Sequencing Reveals Differential miRNA Expression in the Early Development of Broccoli (Brassica oleracea var. italica) Pollen

    PubMed Central

    Li, Hui; Wang, Yu; Wu, Mei; Li, Lihong; Jin, Chuan; Zhang, Qingli; Chen, Chengbin; Song, Wenqin; Wang, Chunguo

    2017-01-01

    Pollen development is an important and complex biological process in the sexual reproduction of flowering plants. Although the cytological characteristics of pollen development are well defined, the regulation of its early stages remains largely unknown. In the present study, miRNAs were explored in the early development of broccoli (Brassica oleracea var. italica) pollen. A total of 333 known miRNAs that originated from 235 miRNA families were detected. Fifty-five novel miRNA candidates were identified. Sixty of the 333 known miRNAs and 49 of the 55 predicted novel miRNAs exhibited significantly differential expression profiling in the three distinct developmental stages of broccoli pollen. Among these differentially expressed miRNAs, miRNAs that would be involved in the developmental phase transition from uninucleate microspores to binucleate pollen grains or from binucleate to trinucleate pollen grains were identified. miRNAs that showed significantly enriched expression in a specific early stage of broccoli pollen development were also observed. In addition, 552 targets for 127 known miRNAs and 69 targets for 40 predicted novel miRNAs were bioinformatically identified. Functional annotation and GO (Gene Ontology) analysis indicated that the putative miRNA targets showed significant enrichment in GO terms that were related to plant organ formation and morphogenesis. Some of enriched GO terms were detected for the targets directly involved in plant male reproduction development. These findings provided new insights into the functions of miRNA-mediated regulatory networks in broccoli pollen development. PMID:28392797

  5. Small RNA Sequencing Reveals Differential miRNA Expression in the Early Development of Broccoli (Brassica oleracea var. italica) Pollen.

    PubMed

    Li, Hui; Wang, Yu; Wu, Mei; Li, Lihong; Jin, Chuan; Zhang, Qingli; Chen, Chengbin; Song, Wenqin; Wang, Chunguo

    2017-01-01

    Pollen development is an important and complex biological process in the sexual reproduction of flowering plants. Although the cytological characteristics of pollen development are well defined, the regulation of its early stages remains largely unknown. In the present study, miRNAs were explored in the early development of broccoli ( Brassica oleracea var. italica ) pollen. A total of 333 known miRNAs that originated from 235 miRNA families were detected. Fifty-five novel miRNA candidates were identified. Sixty of the 333 known miRNAs and 49 of the 55 predicted novel miRNAs exhibited significantly differential expression profiling in the three distinct developmental stages of broccoli pollen. Among these differentially expressed miRNAs, miRNAs that would be involved in the developmental phase transition from uninucleate microspores to binucleate pollen grains or from binucleate to trinucleate pollen grains were identified. miRNAs that showed significantly enriched expression in a specific early stage of broccoli pollen development were also observed. In addition, 552 targets for 127 known miRNAs and 69 targets for 40 predicted novel miRNAs were bioinformatically identified. Functional annotation and GO (Gene Ontology) analysis indicated that the putative miRNA targets showed significant enrichment in GO terms that were related to plant organ formation and morphogenesis. Some of enriched GO terms were detected for the targets directly involved in plant male reproduction development. These findings provided new insights into the functions of miRNA-mediated regulatory networks in broccoli pollen development.

  6. Small RNA profiling and degradome analysis reveal regulation of microRNA in peanut embryogenesis and early pod development.

    PubMed

    Gao, Chao; Wang, Pengfei; Zhao, Shuzhen; Zhao, Chuanzhi; Xia, Han; Hou, Lei; Ju, Zheng; Zhang, Ye; Li, Changsheng; Wang, Xingjun

    2017-03-02

    As a typical geocarpic plant, peanut embryogenesis and pod development are complex processes involving many gene regulatory pathways and controlled by appropriate hormone level. MicroRNAs (miRNAs) are small non-coding RNAs that play indispensable roles in post-transcriptional gene regulation. Recently, identification and characterization of peanut miRNAs has been described. However, whether miRNAs participate in the regulation of peanut embryogenesis and pod development has yet to be explored. In this study, small RNA and degradome libraries from peanut early pod of different developmental stages were constructed and sequenced. A total of 70 known and 24 novel miRNA families were discovered. Among them, 16 miRNA families were legume-specific and 12 families were peanut-specific. 30 known and 10 novel miRNA families were differentially expressed during pod development. In addition, 115 target genes were identified for 47 miRNA families by degradome sequencing. Several new targets that might be specific to peanut were found and further validated by RNA ligase-mediated rapid amplification of 5' cDNA ends (RLM 5'-RACE). Furthermore, we performed profiling analysis of intact and total transcripts of several target genes, demonstrating that SPL (miR156/157), NAC (miR164), PPRP (miR167 and miR1088), AP2 (miR172) and GRF (miR396) are actively modulated during early pod development, respectively. Large numbers of miRNAs and their related target genes were identified through deep sequencing. These findings provided new information on miRNA-mediated regulatory pathways in peanut pod, which will contribute to the comprehensive understanding of the molecular mechanisms that governing peanut embryo and early pod development.

  7. Ancient DNA from South-East Europe Reveals Different Events during Early and Middle Neolithic Influencing the European Genetic Heritage

    PubMed Central

    Hervella, Montserrat; Rotea, Mihai; Izagirre, Neskuts; Constantinescu, Mihai; Alonso, Santos; Ioana, Mihai; Lazăr, Cătălin; Ridiche, Florin; Soficaru, Andrei Dorian; Netea, Mihai G.; de-la-Rua, Concepcion

    2015-01-01

    The importance of the process of Neolithization for the genetic make-up of European populations has been hotly debated, with shifting hypotheses from a demic diffusion (DD) to a cultural diffusion (CD) model. In this regard, ancient DNA data from the Balkan Peninsula, which is an important source of information to assess the process of Neolithization in Europe, is however missing. In the present study we show genetic information on ancient populations of the South-East of Europe. We assessed mtDNA from ten sites from the current territory of Romania, spanning a time-period from the Early Neolithic to the Late Bronze Age. mtDNA data from Early Neolithic farmers of the Starčevo Criş culture in Romania (Cârcea, Gura Baciului and Negrileşti sites), confirm their genetic relationship with those of the LBK culture (Linienbandkeramik Kultur) in Central Europe, and they show little genetic continuity with modern European populations. On the other hand, populations of the Middle-Late Neolithic (Boian, Zau and Gumelniţa cultures), supposedly a second wave of Neolithic migration from Anatolia, had a much stronger effect on the genetic heritage of the European populations. In contrast, we find a smaller contribution of Late Bronze Age migrations to the genetic composition of Europeans. Based on these findings, we propose that permeation of mtDNA lineages from a second wave of Middle-Late Neolithic migration from North-West Anatolia into the Balkan Peninsula and Central Europe represent an important contribution to the genetic shift between Early and Late Neolithic populations in Europe, and consequently to the genetic make-up of modern European populations. PMID:26053041

  8. Ancient DNA from South-East Europe Reveals Different Events during Early and Middle Neolithic Influencing the European Genetic Heritage.

    PubMed

    Hervella, Montserrat; Rotea, Mihai; Izagirre, Neskuts; Constantinescu, Mihai; Alonso, Santos; Ioana, Mihai; Lazăr, Cătălin; Ridiche, Florin; Soficaru, Andrei Dorian; Netea, Mihai G; de-la-Rua, Concepcion

    2015-01-01

    The importance of the process of Neolithization for the genetic make-up of European populations has been hotly debated, with shifting hypotheses from a demic diffusion (DD) to a cultural diffusion (CD) model. In this regard, ancient DNA data from the Balkan Peninsula, which is an important source of information to assess the process of Neolithization in Europe, is however missing. In the present study we show genetic information on ancient populations of the South-East of Europe. We assessed mtDNA from ten sites from the current territory of Romania, spanning a time-period from the Early Neolithic to the Late Bronze Age. mtDNA data from Early Neolithic farmers of the Starčevo Criş culture in Romania (Cârcea, Gura Baciului and Negrileşti sites), confirm their genetic relationship with those of the LBK culture (Linienbandkeramik Kultur) in Central Europe, and they show little genetic continuity with modern European populations. On the other hand, populations of the Middle-Late Neolithic (Boian, Zau and Gumelniţa cultures), supposedly a second wave of Neolithic migration from Anatolia, had a much stronger effect on the genetic heritage of the European populations. In contrast, we find a smaller contribution of Late Bronze Age migrations to the genetic composition of Europeans. Based on these findings, we propose that permeation of mtDNA lineages from a second wave of Middle-Late Neolithic migration from North-West Anatolia into the Balkan Peninsula and Central Europe represent an important contribution to the genetic shift between Early and Late Neolithic populations in Europe, and consequently to the genetic make-up of modern European populations.

  9. Effects of Repeated Concussions and Sex on Early Processing of Emotional Facial Expressions as Revealed by Electrophysiology.

    PubMed

    Carrier-Toutant, Frédérike; Guay, Samuel; Beaulieu, Christelle; Léveillé, Édith; Turcotte-Giroux, Alexandre; Papineau, Samaël D; Brisson, Benoit; D'Hondt, Fabien; De Beaumont, Louis

    2018-05-06

    Concussions affect the processing of emotional stimuli. This study aimed to investigate how sex interacts with concussion effects on early event-related brain potentials (ERP) measures (P1, N1) of emotional facial expressions (EFE) processing in asymptomatic, multi-concussion athletes during an EFE identification task. Forty control athletes (20 females and 20 males) and 43 multi-concussed athletes (22 females and 21 males), recruited more than 3 months after their last concussion, were tested. Participants completed the Beck Depression Inventory II, the Beck Anxiety Inventory, the Post-Concussion Symptom Scale, and an Emotional Facial Expression Identification Task. Pictures of male and female faces expressing neutral, angry, and happy emotions were randomly presented and the emotion depicted had to be identified as fast as possible during EEG acquisition. Relative to controls, concussed athletes of both sex exhibited a significant suppression of P1 amplitude recorded from the dominant right hemisphere while performing the emotional face expression identification task. The present study also highlighted a sex-specific suppression of the N1 component amplitude after concussion which affected male athletes. These findings suggest that repeated concussions alter the typical pattern of right-hemisphere response dominance to EFE in early stages of EFE processing and that the neurophysiological mechanisms underlying the processing of emotional stimuli are distinctively affected across sex. (JINS, 2018, 24, 1-11).

  10. Genome-wide gene expression profiling reveals aberrant MAPK and Wnt signaling pathways associated with early parthenogenesis.

    PubMed

    Liu, Na; Enkemann, Steven A; Liang, Ping; Hersmus, Remko; Zanazzi, Claudia; Huang, Junjiu; Wu, Chao; Chen, Zhisheng; Looijenga, Leendert H J; Keefe, David L; Liu, Lin

    2010-12-01

    Mammalian parthenogenesis could not survive but aborted during mid-gestation, presumably because of lack of paternal gene expression. To understand the molecular mechanisms underlying the failure of parthenogenesis at early stages of development, we performed global gene expression profiling and functional analysis of parthenogenetic blastocysts in comparison with those of blastocysts from normally fertilized embryos. Parthenogenetic blastocysts exhibited changes in the expression of 749 genes, of which 214 had lower expression and 535 showed higher expressions than fertilized embryos using a minimal 1.8-fold change as a cutoff. Genes important for placenta development were decreased in their expression in parthenote blastocysts. Some maternally expressed genes were up-regulated and paternal-related genes were down-regulated. Moreover, aberrantly increased Wnt signaling and reduced mitogen-activated protein kinase (MAPK) signaling were associated with early parthenogenesis. The protein level of extracellular signal-regulated kinase 2 (ERK2) was low in parthenogenetic blastocysts compared with that of fertilized blastocysts 120 h after fertilization. 6-Bromoindirubin-3'-oxime, a specific glycogen synthase kinase-3 (GSK-3) inhibitor, significantly decreased embryo hatching. The expression of several imprinted genes was altered in parthenote blastocysts. Gene expression also linked reduced expression of Xist to activation of X chromosome. Our findings suggest that failed X inactivation, aberrant imprinting, decreased ERK/MAPK signaling and possibly elevated Wnt signaling, and reduced expression of genes for placental development collectively may contribute to abnormal placenta formation and failed fetal development in parthenogenetic embryos.

  11. Historical DNA reveals the demographic history of Atlantic cod (Gadus morhua) in medieval and early modern Iceland

    PubMed Central

    Ólafsdóttir, Guðbjörg Ásta; Westfall, Kristen M.; Edvardsson, Ragnar; Pálsson, Snæbjörn

    2014-01-01

    Atlantic cod (Gadus morhua) vertebrae from archaeological sites were used to study the history of the Icelandic Atlantic cod population in the time period of 1500–1990. Specifically, we used coalescence modelling to estimate population size and fluctuations from the sequence diversity at the cytochrome b (cytb) and Pantophysin I (PanI) loci. The models are consistent with an expanding population during the warm medieval period, large historical effective population size (NE), a marked bottleneck event at 1400–1500 and a decrease in NE in early modern times. The model results are corroborated by the reduction of haplotype and nucleotide variation over time and pairwise population distance as a significant portion of nucleotide variation partitioned across the 1550 time mark. The mean age of the historical fished stock is high in medieval times with a truncation in age in early modern times. The population size crash coincides with a period of known cooling in the North Atlantic, and we conclude that the collapse may be related to climate or climate-induced ecosystem change. PMID:24403343

  12. Transcriptome Assessment of Erythema Migrans Skin Lesions in Patients With Early Lyme Disease Reveals Predominant Interferon Signaling.

    PubMed

    Marques, Adriana; Schwartz, Ira; Wormser, Gary P; Wang, Yanmei; Hornung, Ronald L; Demirkale, Cumhur Y; Munson, Peter J; Turk, Siu-Ping; Williams, Carla; Lee, Chyi-Chia Richard; Yang, Jun; Petzke, Mary M

    2017-12-27

    The most common clinical manifestation of early Lyme disease is the erythema migrans (EM) skin lesion that develops at the tick bite site typically between 7 and 14 days after infection with Borreliella burgdorferi. The host-pathogen interactions that occur in the skin may have a critical role in determining outcome of infection. Gene arrays were used to characterize the global transcriptional alterations in skin biopsy samples of EM lesions from untreated adult patients with Lyme disease in comparison to controls. The transcriptional pattern in EM biopsies consisted of 254 differentially regulated genes (180 induced and 74 repressed) characterized by the induction of chemokines, cytokines, Toll-like receptors, antimicrobial peptides, monocytoid cell activation markers, and numerous genes annotated as interferon (IFN)-inducible. The IFN-inducible genes included 3 transcripts involved in tryptophan catabolism (IDO1, KMO, KYNU) that play a pivotal role in immune evasion by certain other microbial pathogens by driving the differentiation of regulatory T cells. This is the first study to globally assess the human skin transcriptional response during early Lyme disease. Borreliella burgdorferi elicits a predominant IFN signature in the EM lesion, suggesting a potential mechanism for spirochetal dissemination via IDO1-mediated localized immunosuppression. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  13. Historical DNA reveals the demographic history of Atlantic cod (Gadus morhua) in medieval and early modern Iceland.

    PubMed

    Ólafsdóttir, Guðbjörg Ásta; Westfall, Kristen M; Edvardsson, Ragnar; Pálsson, Snæbjörn

    2014-02-22

    Atlantic cod (Gadus morhua) vertebrae from archaeological sites were used to study the history of the Icelandic Atlantic cod population in the time period of 1500-1990. Specifically, we used coalescence modelling to estimate population size and fluctuations from the sequence diversity at the cytochrome b (cytb) and Pantophysin I (PanI) loci. The models are consistent with an expanding population during the warm medieval period, large historical effective population size (NE), a marked bottleneck event at 1400-1500 and a decrease in NE in early modern times. The model results are corroborated by the reduction of haplotype and nucleotide variation over time and pairwise population distance as a significant portion of nucleotide variation partitioned across the 1550 time mark. The mean age of the historical fished stock is high in medieval times with a truncation in age in early modern times. The population size crash coincides with a period of known cooling in the North Atlantic, and we conclude that the collapse may be related to climate or climate-induced ecosystem change.

  14. Blind Quantum Signature with Blind Quantum Computation

    NASA Astrophysics Data System (ADS)

    Li, Wei; Shi, Ronghua; Guo, Ying

    2017-04-01

    Blind quantum computation allows a client without quantum abilities to interact with a quantum server to perform a unconditional secure computing protocol, while protecting client's privacy. Motivated by confidentiality of blind quantum computation, a blind quantum signature scheme is designed with laconic structure. Different from the traditional signature schemes, the signing and verifying operations are performed through measurement-based quantum computation. Inputs of blind quantum computation are securely controlled with multi-qubit entangled states. The unique signature of the transmitted message is generated by the signer without leaking information in imperfect channels. Whereas, the receiver can verify the validity of the signature using the quantum matching algorithm. The security is guaranteed by entanglement of quantum system for blind quantum computation. It provides a potential practical application for e-commerce in the cloud computing and first-generation quantum computation.

  15. The efficacy of early initiated, supervised, progressive resistance training compared to unsupervised, home-based exercise after unicompartmental knee arthroplasty: a single-blinded randomized controlled trial.

    PubMed

    Jørgensen, Peter B; Bogh, Søren B; Kierkegaard, Signe; Sørensen, Henrik; Odgaard, Anders; Søballe, Kjeld; Mechlenburg, Inger

    2017-01-01

    To examine if supervised progressive resistance training was superior to home-based exercise in rehabilitation after unicompartmental knee arthroplasty. Single blinded, randomized clinical trial. Surgery, progressive resistance training and testing was carried out at Aarhus University Hospital and home-based exercise was carried out in the home of the patient. Fifty five patients were randomized to either progressive resistance training or home-based exercise. Patients were randomized to either progressive resistance training (home based exercise five days/week and progressive resistance training two days/week) or control group (home based exercise seven days/week). Preoperative assessment, 10-week (primary endpoint) and one-year follow-up were performed for leg extension power, spatiotemporal gait parameters and knee injury and osteoarthritis outcome score (KOOS). Forty patients (73%) completed 1-year follow-up. Patients in the progressive resistance training group participated in average 11 of 16 training sessions. Leg extension power increased from baseline to 10-week follow-up in progressive resistance training group (progressive resistance training: 0.28 W/kg, P= 0.01, control group: 0.01 W/kg, P=0.93) with no between-group difference. Walking speed and KOOS scores increased from baseline to 10-week follow-up in both groups with no between-group difference (six minutes walk test P=0.63, KOOS P>0.29). Progressive resistance training two days/week combined with home based exercise five days/week was not superior to home based exercise seven days/week in improving leg extension power of the operated leg.

  16. Beneficial immunostimulatory effect of short-term Chlorella supplementation: enhancement of Natural Killer cell activity and early inflammatory response (Randomized, double-blinded, placebo-controlled trial)

    PubMed Central

    2012-01-01

    Background In vitro and animal studies have demonstrated that Chlorella is a potent biological response modifier on immunity. However, there were no direct evidences for the effect of Chlorella supplementation on immune/inflammation response in healthy humans. Methods This study was designed for an 8-week randomized, double-blinded, placebo-controlled trial: 5g of Chlorella (n=23) or Placebo (n=28) as form of tablets. Mainly, cytotoxic activities of Natural killer (NK) cells and serum concentrations of interferon-γ, interleukin-1β and interleukin-12 were measured. Results After the 8-week, serum concentrations of interferon-γ (p<0.05) and interleukin-1β (p<0.001) significantly increased and that of interleukin-12 (p<0.1) tended to increase in the Chlorella group. The increments of these cytokines after the intervention were significantly bigger in the Chlorella group than those in the placebo group. In addition, NK cell activities (%) were significantly increased in Chlorella group, but not in Placebo group. The increments of NK cell activities (%) were also significantly bigger in the Chlorella group than the placebo group. Additionally, changed levels of NK cell activity were positively correlated with those of serum interleukin-1β (r=0.280, p=0.047) and interferon-γ (r=0.271, p<0.005). Signficantly positive correlations were also observed among the changed levels of serum cytokines; between interferon-γ and interleukin-1β (r=0.448, p<0.001), between interleukin-12 and interleukin-1β (r=0.416, p=0.003) and between interleukin-12 and interferon-γ (r=0.570, p<001). Conclusion These results may suggest a beneficial immunostimulatory effect of short-term Chlorella supplementation which enhances the NK cell activity and produces interferon-γ and interleukin-12 as well as interleukin-1β, the Th-1 cell-induced cytokines in healthy people. PMID:22849818

  17. Shape Perception and Navigation in Blind Adults

    PubMed Central

    Gori, Monica; Cappagli, Giulia; Baud-Bovy, Gabriel; Finocchietti, Sara

    2017-01-01

    Different sensory systems interact to generate a representation of space and to navigate. Vision plays a critical role in the representation of space development. During navigation, vision is integrated with auditory and mobility cues. In blind individuals, visual experience is not available and navigation therefore lacks this important sensory signal. In blind individuals, compensatory mechanisms can be adopted to improve spatial and navigation skills. On the other hand, the limitations of these compensatory mechanisms are not completely clear. Both enhanced and impaired reliance on auditory cues in blind individuals have been reported. Here, we develop a new paradigm to test both auditory perception and navigation skills in blind and sighted individuals and to investigate the effect that visual experience has on the ability to reproduce simple and complex paths. During the navigation task, early blind, late blind and sighted individuals were required first to listen to an audio shape and then to recognize and reproduce it by walking. After each audio shape was presented, a static sound was played and the participants were asked to reach it. Movements were recorded with a motion tracking system. Our results show three main impairments specific to early blind individuals. The first is the tendency to compress the shapes reproduced during navigation. The second is the difficulty to recognize complex audio stimuli, and finally, the third is the difficulty in reproducing the desired shape: early blind participants occasionally reported perceiving a square but they actually reproduced a circle during the navigation task. We discuss these results in terms of compromised spatial reference frames due to lack of visual input during the early period of development. PMID:28144226

  18. Effects of modified constraint-induced movement therapy with trunk restraint in early stroke patients: A single-blinded, randomized, controlled, pilot trial.

    PubMed

    Bang, Dae-Hyouk; Shin, Won-Seob; Choi, Ho-Suk

    2018-01-01

    Reducing compensatory strategies during repetitive upper-limb training may be helpful in relearning motor skills. To explore the effects of modified constraint-induced movement therapy (mCIMT), additionally modified by adding trunk restraint (TR), on upper-limb function and activities of daily living (ADLs) in early post-stroke patients. Twenty-four participants with early stroke were randomly assigned to mCIMT combined with TR (mCIMT + TR) or mCIMT alone. Each group underwent twenty sessions (1 h/d, 5 d/wk for 4 weeks). Patients were assessed with the action research arm test (ARAT), the Fugl-Meyer Assessment-Upper extremity (FMA-UE), the Modified Barthel index (MBI), the Maximal elbow extension angle during reaching (MEEAR), and Motor Activity Logs (MAL-AOU and MAL-QOM). The mCIMT + TR group exhibited greater improvement in the ARAT, FMA-UE, MBI, MEEAR, and MAL-AOU, and MAL-QOM than the mCIMT group. Statistical analyses showed significant differences in ARAT (P = 0.003), FMA-UE (P = 0.042), MBI (P = 0.001), MEEAR (P = 0.002), and MAL-AOU (P = 0.005) between the groups. Modified CIMT combined with TR may be more effective than mCIMT alone in improving upper-limb function and ADLs in patients with early stroke.

  19. Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment.

    PubMed

    Chaudhry, Imran B; Hallak, Jaime; Husain, Nusrat; Minhas, Fareed; Stirling, John; Richardson, Paul; Dursun, Serdar; Dunn, Graham; Deakin, Bill

    2012-09-01

    The onset and early course of schizophrenia is associated with subtle loss of grey matter which may be responsible for the evolution and persistence of symptoms such as apathy, emotional blunting, and social withdrawal. Such 'negative' symptoms are unaffected by current antipsychotic therapies. There is evidence that the antibiotic minocycline has neuroprotective properties. We investigated whether the addition of minocycline to treatment as usual (TAU) for 1 year in early psychosis would reduce negative symptoms compared with placebo. In total, 144 participants within 5 years of first onset in Brazil and Pakistan were randomised to receive TAU plus placebo or minocycline. The primary outcome measures were the negative and positive syndrome ratings using the Positive and Negative Syndrome Scale. Some 94 patients completed the trial. The mean improvement in negative symptoms for the minocycline group was 9.2 and in the placebo group 4.7, an adjusted difference of 3.53 (s.e. 1.01) 95% CI: 1.55, 5.51; p < 0.001 in the intention-to-treat population. The effect was present in both countries. The addition of minocycline to TAU early in the course of schizophrenia predominantly improves negative symptoms. Whether this is mediated by neuroprotective, anti-inflammatory or others actions is under investigation.

  20. [Aiming for zero blindness].

    PubMed

    Nakazawa, Toru

    2015-03-01

    field sectors within a 10 x 10 grid displayed by an OCT map of the macula. By analyzing both the visual field and the macular map sectors, we anticipate that a more accurate and sensitive detection of glaucoma progression can become possible. We also used laser speckle flowgraphy (LSFG) to assess optic nerve blood flow. We found that compared to healthy eyes, eyes with early-stage NTG had decreased blood flow, and the peak of the blood flow wave form of each heartbeat was delayed. Finally, we used a method combining swept source OCT (SS-OCT) and newly developed analysis software to reconstruct the entire lamina cribrosa, a structure situated deep in the optic nerve head. This morphological analysis returned preliminary data suggesting that alterations in the morphology of the lamina cribrosa are already present in the early stages of glaucoma. This result indicates that axonal injury, mediated by morphological abnormalities of the lamina cribrosa, is involved in the pathogenesis of glaucoma. The next topic discussed is the pathology-based drug research and development, focusing on the use of comprehensive gene expression analysis and the development of molecule-targeting drugs in a murine model of optic nerve injury. Learning from clinical data on glaucoma and the lamina cribrosa, we carried out basic research to first determine what factors regulate axonal injury, and then develop drugs targeting these factors. Specifically, we performed a comprehensive gene expression analysis, using a next generation sequencer, and pathway analysis of retinal samples obtained from a murine model of axonal injury. This analysis revealed a characteristic upregulation of genes (such as Chop) that belongs to the endoplasmic reticulum stress pathway. An immunohistological analysis revealed that these changes in gene expression took place in the retinal ganglion cells, suggesting that endoplasmic reticulum stress molecules may be suitable therapeutic targets. Among these molecules, we

  1. Combined Chromatin and Expression Analysis Reveals Specific Regulatory Mechanisms within Cytokine Genes in the Macrophage Early Immune Response

    PubMed Central

    Emanuelsson, Olof; Sennblad, Bengt; Pirmoradian Najafabadi, Mohammad; Folkersen, Lasse; Mälarstig, Anders; Lagergren, Jens; Eriksson, Per; Hamsten, Anders; Odeberg, Jacob

    2012-01-01

    Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS). To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches - gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq) analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac) and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII), which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of up-regulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF), was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines), was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/−LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40%) was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at the

  2. Comparison of multi-modal early oral nutrition for the tolerance of oral nutrition with conventional care after major abdominal surgery: a prospective, randomized, single-blind trial.

    PubMed

    Sun, Da-Li; Li, Wei-Ming; Li, Shu-Min; Cen, Yun-Yun; Xu, Qing-Wen; Li, Yi-Jun; Sun, Yan-Bo; Qi, Yu-Xing; Lin, Yue-Ying; Yang, Ting; Lu, Qi-Ping; Xu, Peng-Yuan

    2017-02-10

    Early oral nutrition (EON) has been shown to improve recovery of gastrointestinal function, length of stay and mortality after abdominal surgery; however, early oral nutrition often fails during the first week after surgery. Here, a multi-modal early oral nutrition program is introduced to promote recovery of gastrointestinal function and tolerance of oral nutrition. Consecutive patients scheduled for abdominal surgery were randomized to the multimodal EON group or a group receiving conventional care. The primary endpoint was the time of first defecation. The secondary endpoints were outcomes and the cost-effectiveness ratio in treating infectious complications. The rate of infectious-free patients was regarded as the index of effectiveness. One hundred seven patients were randomly assigned to groups. Baseline characteristics were similar for both groups. In intention-to-treat analysis, the success rate of oral nutrition during the first week after surgery in the multimodal EON group was 44 (83.0%) versus 31 (57.4%) in the conventional care group (P = 0.004). Time to first defecation, time to flatus, recovery time of bowel sounds, and prolonged postoperative ileus were all less in the multimodal EON group (P < 0.05). The median postoperative length of stay in the multimodal EON group was 8 days (6, 12) versus 10 days (7, 18) in the conventional care group (P < 0.001). The total cost of treatment and nutritional support were also less in the multi-modal early oral nutrition group (P < 0.001). The effectiveness was 84.9 and 79.9% in the multimodal EON and conventional care group, respectively (P = 0.475). However, the cost-effectiveness ratio was USD 537.6 (506.1, 589.3) and USD 637.8 (593.9, 710.3), respectively (P < 0.001). The multi-modal early oral nutrition program was an effective way to improve tolerance of oral nutrition during the first week after surgery, decrease the length of stay and improve cost-effectiveness after abdominal

  3. Automated analysis of connected speech reveals early biomarkers of Parkinson's disease in patients with rapid eye movement sleep behaviour disorder.

    PubMed

    Hlavnička, Jan; Čmejla, Roman; Tykalová, Tereza; Šonka, Karel; Růžička, Evžen; Rusz, Jan

    2017-02-02

    For generations, the evaluation of speech abnormalities in neurodegenerative disorders such as Parkinson's disease (PD) has been limited to perceptual tests or user-controlled laboratory analysis based upon rather small samples of human vocalizations. Our study introduces a fully automated method that yields significant features related to respiratory deficits, dysphonia, imprecise articulation and dysrhythmia from acoustic microphone data of natural connected speech for predicting early and distinctive patterns of neurodegeneration. We compared speech recordings of 50 subjects with rapid eye movement sleep behaviour disorder (RBD), 30 newly diagnosed, untreated PD patients and 50 healthy controls, and showed that subliminal parkinsonian speech deficits can be reliably captured even in RBD patients, which are at high risk of developing PD or other synucleinopathies. Thus, automated vocal analysis should soon be able to contribute to screening and diagnostic procedures for prodromal parkinsonian neurodegeneration in natural environments.

  4. Weighted gene co-expression network analysis reveals potential genes involved in early metamorphosis process in sea cucumber Apostichopus japonicus.

    PubMed

    Li, Yongxin; Kikuchi, Mani; Li, Xueyan; Gao, Qionghua; Xiong, Zijun; Ren, Yandong; Zhao, Ruoping; Mao, Bingyu; Kondo, Mariko; Irie, Naoki; Wang, Wen

    2018-01-01

    Sea cucumbers, one main class of Echinoderms, have a very fast and drastic metamorphosis process during their development. However, the molecular basis under this process remains largely unknown. Here we systematically examined the gene expression profiles of Japanese common sea cucumber (Apostichopus japonicus) for the first time by RNA sequencing across 16 developmental time points from fertilized egg to juvenile stage. Based on the weighted gene co-expression network analysis (WGCNA), we identified 21 modules. Among them, MEdarkmagenta was highly expressed and correlated with the early metamorphosis process from late auricularia to doliolaria larva. Furthermore, gene enrichment and differentially expressed gene analysis identified several genes in the module that may play key roles in the metamorphosis process. Our results not only provide a molecular basis for experimentally studying the development and morphological complexity of sea cucumber, but also lay a foundation for improving its emergence rate. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. An Alternative Model for the Early Peopling of Southern South America Revealed by Analyses of Three Mitochondrial DNA Haplogroups

    PubMed Central

    de Saint Pierre, Michelle; Bravi, Claudio M.; Motti, Josefina M. B.; Fuku, Noriyuki; Tanaka, Masashi; Llop, Elena; Bonatto, Sandro L.; Moraga, Mauricio

    2012-01-01

    After several years of research, there is now a consensus that America was populated from Asia through Beringia, probably at the end of the Pleistocene. But many details such as the timing, route(s), and origin of the first settlers remain uncertain. In the last decade genetic evidence has taken on a major role in elucidating the peopling of the Americas. To study the early peopling of South America, we sequenced the control region of mitochondrial DNA from 300 individuals belonging to indigenous populations of Chile and Argentina, and also obtained seven complete mitochondrial DNA sequences. We identified two novel mtDNA monophyletic clades, preliminarily designated B2l and C1b13, which together with the recently described D1g sub-haplogroup have locally high frequencies and are basically restricted to populations from the extreme south of South America. The estimated ages of D1g and B2l, about ∼15,000 years BP, together with their similar population dynamics and the high haplotype diversity shown by the networks, suggests that they probably appeared soon after the arrival of the first settlers and agrees with the dating of the earliest archaeological sites in South America (Monte Verde, Chile, 14,500 BP). One further sub-haplogroup, D4h3a5, appears to be restricted to Fuegian-Patagonian populations and reinforces our hypothesis of the continuity of the current Patagonian populations with the initial founders. Our results indicate that the extant native populations inhabiting South Chile and Argentina are a group which had a common origin, and suggest a population break between the extreme south of South America and the more northern part of the continent. Thus the early colonization process was not just an expansion from north to south, but also included movements across the Andes. PMID:22970129

  6. An alternative model for the early peopling of southern South America revealed by analyses of three mitochondrial DNA haplogroups.

    PubMed

    de Saint Pierre, Michelle; Bravi, Claudio M; Motti, Josefina M B; Fuku, Noriyuki; Tanaka, Masashi; Llop, Elena; Bonatto, Sandro L; Moraga, Mauricio

    2012-01-01

    After several years of research, there is now a consensus that America was populated from Asia through Beringia, probably at the end of the Pleistocene. But many details such as the timing, route(s), and origin of the first settlers remain uncertain. In the last decade genetic evidence has taken on a major role in elucidating the peopling of the Americas. To study the early peopling of South America, we sequenced the control region of mitochondrial DNA from 300 individuals belonging to indigenous populations of Chile and Argentina, and also obtained seven complete mitochondrial DNA sequences. We identified two novel mtDNA monophyletic clades, preliminarily designated B2l and C1b13, which together with the recently described D1g sub-haplogroup have locally high frequencies and are basically restricted to populations from the extreme south of South America. The estimated ages of D1g and B2l, about ~15,000 years BP, together with their similar population dynamics and the high haplotype diversity shown by the networks, suggests that they probably appeared soon after the arrival of the first settlers and agrees with the dating of the earliest archaeological sites in South America (Monte Verde, Chile, 14,500 BP). One further sub-haplogroup, D4h3a5, appears to be restricted to Fuegian-Patagonian populations and reinforces our hypothesis of the continuity of the current Patagonian populations with the initial founders. Our results indicate that the extant native populations inhabiting South Chile and Argentina are a group which had a common origin, and suggest a population break between the extreme south of South America and the more northern part of the continent. Thus the early colonization process was not just an expansion from north to south, but also included movements across the Andes.

  7. Specific cerebellar activation during Braille reading in blind subjects.

    PubMed

    Gizewski, Elke R; Timmann, Dagmar; Forsting, Michael

    2004-07-01

    The traditional view that the cerebellum is involved only in the control of movements has been changed recently. It has been suggested that the human cerebellum is involved in cognition and language. Likewise, besides cortical activity in sensorimotor and visual areas, an increased global activation of the cerebellum has been revealed during Braille reading in blind subjects. Our purpose was to investigate whether there is cerebellar activation during Braille reading by blind subjects other than sensorimotor activation related to finger movements. Early blind and normal sighted subjects were studied with functional magnetic resonance imaging (fMRI) during Braille reading, tactile discrimination of nonsense dots, dots forming symbols, and finger tapping. The experiments were done in block design. Echo planar imaging sequences were carried out on a 1.5-T MR scanner. All blind individuals reading Braille showed robust activation of the posterior and lateral aspects of cerebellar hemispheral lobules Crus I bilaterally but more predominately on the right side. Additionally, activation was present in the medial cerebellum within lobules IV, V, and VIIIA, predominantly on the right. Discriminating nonsense dots did not reveal any activation of Crus I, but did reveal activation within the medial part of lobules IV, V, and VIIIA, predominately on the right. Analysis of sighted subjects during reading of printed text revealed activation of the posterolateral cerebellar hemisphere in Crus I bilaterally, predominantly on the right. Tactile analysis of dots representing symbols revealed an activation in lobules IV and VIII and in right Crus II but not in Crus I. In conclusion, parts of cerebellar activation during Braille reading in blind subjects (i.e., within lobules IV, V, and VIII) overlap with the known hand representation within the cerebellum and are likely related to the sensorimotor part of the task. Cerebellar activation during Braille reading within bilateral Crus I

  8. Epidemiological evaluation quality of life in patients suffering from early rheumatoid arthritis: a pragmatic, prospective, randomized, blind allocation controlled of a modular program group intervention.

    PubMed

    Yousefi, Hadi; Chopra, Arvind; Farrokhseresht, Reza; Sarmukaddam, Sanjeev; Noghabi, Fariba Asadi; Bedekar, Nilima; Madani, Abdolhosain

    2015-01-01

    Epidemiology has taken on new roles in the management of health care services. In this study, we developed a non-pharmacological self-management modular program group intervention and evaluated its efficacy as an adjunct therapy in patients suffering from early rheumatoid arthritis (RA). Patients were randomized to either participate in a non-equivalent intervention group along with the standard of care or only receive standard-of-care treatment at a community rheumatology center. The outcomes measured were a pain visual analog scale (VAS), patient general health (GH) on a VAS, and the Short Form 36 Health Survey version 2 scale measuring quality of life. These parameters were evaluated in the first week to obtain baseline values, and at 20, 32, 48, and 60 weeks to evaluate the efficacy of the intervention group. The patients were randomized, with 100 patients in the intervention group and 106 in the control group. The intervention and control groups were similar with regard to the percentage of women (86% vs. 89.6%), tobacco usage (25% vs. 19.8%), mean age (42.6±13.2 years vs. 46.6±10.9 years), and disease duration (15.3±6.7 months vs. 14.5±6.6 months). The mean outcomes were significantly different between the two groups, and post-hoc pairwise analysis demonstrated significant deterioration in the control group in contrast to improvement in the intervention group at the second, third, fourth, and fifth evaluations. Improvements were often seen as early as the 12-week and 24-week follow-up visits. Epidemiology contributes to the evaluation of how well specific therapies or other health interventions prevent or control health problems. The modular program group intervention implemented in this study appears to be a suitable and feasible method to facilitate much more comprehensive management of early RA in socioeconomically challenged communities.

  9. Epidemiological evaluation quality of life in patients suffering from early rheumatoid arthritis: a pragmatic, prospective, randomized, blind allocation controlled of a modular program group intervention

    PubMed Central

    2015-01-01

    OBJECTIVES: Epidemiology has taken on new roles in the management of health care services. In this study, we developed a non-pharmacological self-management modular program group intervention and evaluated its efficacy as an adjunct therapy in patients suffering from early rheumatoid arthritis (RA). METHODS: Patients were randomized to either participate in a non-equivalent intervention group along with the standard of care or only receive standard-of-care treatment at a community rheumatology center. The outcomes measured were a pain visual analog scale (VAS), patient general health (GH) on a VAS, and the Short Form 36 Health Survey version 2 scale measuring quality of life. These parameters were evaluated in the first week to obtain baseline values, and at 20, 32, 48, and 60 weeks to evaluate the efficacy of the intervention group. RESULTS: The patients were randomized, with 100 patients in the intervention group and 106 in the control group. The intervention and control groups were similar with regard to the percentage of women (86% vs. 89.6%), tobacco usage (25% vs. 19.8%), mean age (42.6±13.2 years vs. 46.6±10.9 years), and disease duration (15.3±6.7 months vs. 14.5±6.6 months). The mean outcomes were significantly different between the two groups, and post-hoc pairwise analysis demonstrated significant deterioration in the control group in contrast to improvement in the intervention group at the second, third, fourth, and fifth evaluations. Improvements were often seen as early as the 12-week and 24-week follow-up visits. CONCLUSIONS: Epidemiology contributes to the evaluation of how well specific therapies or other health interventions prevent or control health problems. The modular program group intervention implemented in this study appears to be a suitable and feasible method to facilitate much more comprehensive management of early RA in socioeconomically challenged communities. PMID:26552423

  10. In vivo whole animal body imaging reveals colonization of Chlamydia muridarum to the lower genital tract at early stages of infection.

    PubMed

    Gupta, Rishein; Wali, Shradha; Yu, Jieh-Juen; Chambers, James P; Zhong, Guangming; Murthy, Ashlesh K; Bakar, Sazaly Abu; Guentzel, M N; Arulanandam, Bernard P

    2014-10-01

    The leading cause of sexually transmitted bacterial infection is Chlamydia trachomatis. The aim of this study is to investigate the early events in colonization of this bacterium within the murine genital tract. An in vivo animal body imaging technology was used to track fluorophore labeled C. muridarum elementary bodies (EBs) inoculated intravaginally in C57BL/6 mice during the first 24 h of infection. Ascension of viable EBs was observed (1) to be localized to the lower regions of the murine genital tract within the first 24 h post challenge and (2) was dose independent during this early exposure period. Molecular detection revealed enhanced bacterial load in lower regions of the genital tract with increasing bacterial load in the upper region beginning 12 h post inoculation. This study provides additional insight into chlamydial colonization in the murine genital tract during the first 12-24 h following inoculation.

  11. The effect of caudal vs intravenous morphine on early extubation and postoperative analgesic requirements for stage 2 and 3 single-ventricle palliation: a double blind randomized trial.

    PubMed

    Stuth, Eckehard A E; Berens, Richard J; Staudt, Susan R; Robertson, Frederick A; Scott, John P; Stucke, Astrid G; Hoffman, George M; Troshynski, Todd J; Tweddell, James S T; Zuperku, Edward J

    2011-04-01

    High-dose single-shot caudal morphine has been postulated to facilitate early extubation and to lower initial analgesic requirements after staged single-ventricle (SV) palliation. With Institutional Review Board approval and written informed parental consent, 64 SV children aged 75-1667 days were randomized to pre-incisional caudal morphine-bupivacaine (100 μg·kg(-1) morphine (concentration 0.1%), mixed with 0.25% bupivacaine with 1 : 200,000 epinephrine, total 1 ml·kg(-1)) and postcardiopulmonary bypass (CPB) intravenous (IV) droperidol (75 μg·kg(-1)) ('active caudal group') or pre-incisional caudal saline (1 ml·kg(-1)) and post-CPB IV morphine (150 μg·kg(-1)) with droperidol (75 μg·kg(-1)) ('active IV group'). Assignment remained concealed from families and the care teams throughout the trial. Early extubation failure rates (primary or reintubation within 24 h), time to first postoperative rescue morphine analgesia, and 12-h postoperative morphine requirements were assessed for extubated patients. Thirty-one (12 stage 2) SV patients received caudal morphine and 32 (15 stage 2) received IV morphine. Extubation failure rates were 6/31 (19%) for caudal and 5/32 (16%) for IV morphine. For successfully extubated patients (n = 54), active caudal treatment significantly delayed the need for postoperative rescue morphine in stage 3 patients (P = 0.02) but not in stage 2 patients (P = 0.189) (Kaplan-Meier survival analysis with LogRank test). The reduction in 12-h postoperative morphine requirements with active caudal treatment did not reach significance (P = 0.085) but morphine requirements were significantly higher for stage 2 compared with stage 3 patients (P < 0.001) (two-way anova in n = 50 extubated patients). High-dose caudal morphine with bupivacaine delayed the need for rescue morphine analgesia in stage 3 patients. All stage 2 patients required early rescue morphine and had significantly higher postoperative 12-h morphine requirements than stage 3

  12. Behavioral Characterization of A53T Mice Reveals Early and Late Stage Deficits Related to Parkinson’s Disease

    PubMed Central

    Paumier, Katrina L.; Sukoff Rizzo, Stacey J.; Berger, Zdenek; Chen, Yi; Gonzales, Cathleen; Kaftan, Edward; Li, Li; Lotarski, Susan; Monaghan, Michael; Shen, Wei; Stolyar, Polina; Vasilyev, Dmytro; Zaleska, Margaret; D. Hirst, Warren; Dunlop, John

    2013-01-01

    Parkinson's disease (PD) pathology is characterized by the formation of intra-neuronal inclusions called Lewy bodies, which are comprised of alpha-synuclein (α-syn). Duplication, triplication or genetic mutations in α-syn (A53T, A30P and E46K) are linked to autosomal dominant PD; thus implicating its role in the pathogenesis of PD. In both PD patients and mouse models, there is increasing evidence that neuronal dysfunction occurs before the accumulation of protein aggregates (i.e., α-syn) and neurodegeneration. Characterization of the timing and nature of symptomatic dysfunction is important for understanding the impact of α-syn on disease progression. Furthermore, this knowledge is essential for identifying pathways and molecular targets for therapeutic intervention. To this end, we examined various functional and morphological endpoints in the transgenic mouse model expressing the human A53T α-syn variant directed by the mouse prion promoter at specific ages relating to disease progression (2, 6 and 12 months of age). Our findings indicate A53T mice develop fine, sensorimotor, and synaptic deficits before the onset of age-related gross motor and cognitive dysfunction. Results from open field and rotarod tests show A53T mice develop age-dependent changes in locomotor activity and reduced anxiety-like behavior. Additionally, digigait analysis shows these mice develop an abnormal gait by 12 months of age. A53T mice also exhibit spatial memory deficits at 6 and 12 months, as demonstrated by Y-maze performance. In contrast to gross motor and cognitive changes, A53T mice display significant impairments in fine- and sensorimotor tasks such as grooming, nest building and acoustic startle as early as 1–2 months of age. These mice also show significant abnormalities in basal synaptic transmission, paired-pulse facilitation and long-term depression (LTD). Combined, these data indicate the A53T model exhibits early- and late-onset behavioral and synaptic impairments

  13. Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (III) Clinical responses of early-postmenopausal women to Maca in double blind, randomized, Placebo-controlled, crossover configuration, outpatient study

    PubMed Central

    Meissner, H. O.; Mscisz, A.; Reich-Bilinska, H.; Mrozikiewicz, P.; Bobkiewicz-Kozlowska, T.; Kedzia, B.; Lowicka, A.; Barchia, I.

    2006-01-01

    This is the second, conclusive part of the clinical study on clinical responses of early-postmenopausal women to standardized doses of pre-Gelatinized Organic Maca (Maca-GO). Total of 34 Caucasian women volunteers participated in a double-blind, randomized, four months outpatient crossover configuration Trial. After fulfilling the criteria of being early-postmenopausal: blood Estrogen (E2<40 pg/ml) and Follicle Stimulating Hormone (FSH>30 IU/ml) at admission, they were randomly allocated to Placebo (P) and Maca-GO (M) treatments (2 groups of 11 participants each). Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day). At admission and follow-up monthly intervals, body mass index (BMI), blood pressure, levels of gonadal, pituitary, thyroid and adrenal hormones, lipids and key minerals were measured. Bone markers were determined after four months M and P use in 12 participants. Menopausal symptoms were assessed according to Greene’s Score (GMS) and Kupperman’s Index (KMI). Data were analyzed using multivariate technique on blocs of monthly. Results and canonical variate technique was applied to GMS and KMI matrices. Two months application of Maca-GO stimulated (P<0.05) production of E2, suppressed (P<0.05) blood FSH, Thyroid (T3) and Adrenocorticotropic hormones, Cortisol, and BMI, increased (P<0.05) low density lipoproteins, blood Iron and alleviated (P<0.001) menopausal symptoms. Maca-GO noticeably increased bone density markers. In conclusion, Maca-GO applied to early-postmenopausal women (i) acted as a toner of hormonal processes along the Hypothalamus-Pituitary-Ovarian axis, (ii) balanced hormone levels and (iii) relieved symptoms of menopausal discomfort, (hot flushes and night sweating in particular), thus, (iv) exhibited a distinctive function peculiar to adaptogens, providing an alternative non-hormonal plant option to reduce dependence on hormone therapy programs (HRT). PMID

  14. Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (III) Clinical responses of early-postmenopausal women to Maca in double blind, randomized, Placebo-controlled, crossover configuration, outpatient study.

    PubMed

    Meissner, H O; Mscisz, A; Reich-Bilinska, H; Mrozikiewicz, P; Bobkiewicz-Kozlowska, T; Kedzia, B; Lowicka, A; Barchia, I

    2006-12-01

    This is the second, conclusive part of the clinical study on clinical responses of early-postmenopausal women to standardized doses of pre-Gelatinized Organic Maca (Maca-GO). Total of 34 Caucasian women volunteers participated in a double-blind, randomized, four months outpatient crossover configuration Trial. After fulfilling the criteria of being early-postmenopausal: blood Estrogen (E2<40 pg/ml) and Follicle Stimulating Hormone (FSH>30 IU/ml) at admission, they were randomly allocated to Placebo (P) and Maca-GO (M) treatments (2 groups of 11 participants each). Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day). At admission and follow-up monthly intervals, body mass index (BMI), blood pressure, levels of gonadal, pituitary, thyroid and adrenal hormones, lipids and key minerals were measured. Bone markers were determined after four months M and P use in 12 participants. Menopausal symptoms were assessed according to Greene's Score (GMS) and Kupperman's Index (KMI). Data were analyzed using multivariate technique on blocs of monthly. Results and canonical variate technique was applied to GMS and KMI matrices. Two months application of Maca-GO stimulated (P<0.05) production of E2, suppressed (P<0.05) blood FSH, Thyroid (T3) and Adrenocorticotropic hormones, Cortisol, and BMI, increased (P<0.05) low density lipoproteins, blood Iron and alleviated (P<0.001) menopausal symptoms. Maca-GO noticeably increased bone density markers. In conclusion, Maca-GO applied to early-postmenopausal women (i) acted as a toner of hormonal processes along the Hypothalamus-Pituitary-Ovarian axis, (ii) balanced hormone levels and (iii) relieved symptoms of menopausal discomfort, (hot flushes and night sweating in particular), thus, (iv) exhibited a distinctive function peculiar to adaptogens, providing an alternative non-hormonal plant option to reduce dependence on hormone therapy programs (HRT).

  15. Can levothyroxine treatment reduce urinary albumin excretion rate in patients with early type 2 diabetic nephropathy and subclinical hypothyroidism? A randomized double-blind and placebo-controlled study.

    PubMed

    Liu, Peng; Liu, Ruidong; Chen, Xia; Chen, Yingying; Wang, Debao; Zhang, Fengmei; Wang, Yangang

    2015-12-01

    To investigate the effect of levothyroxine (LT4) therapy on urinary albumin excretion rate (UAER) in early type 2 diabetic nephropathy (DN) and subclinical hypothyroidism (SCH) patients with mildly increased thyroid stimulating hormone (TSH) levels and serum thyroid peroxidase antibody (TPO-Ab) positivity. Application of randomized double-blind and placebo-controlled methods. A total of 136 normotensive patients with early type 2 DN and SCH (TSH 4.0-7.0 mIU/L and TPO-Ab positive) were selected, and were randomly divided into two groups for LT4 or placebo treatments, respectively. Changes in UAER, serum creatinine, glomerular filtration rate (GFR), blood pressure, serum uric acid and lipids in patients before and after 48 weeks of treatment were examined and compared between groups. There were no statistically significant differences in the baseline characteristics of study participants between two treatment groups (p > 0.05 for all). After 48 weeks of treatment, compared to the placebo treatment, the LT4 treatment was more effective in reducing total cholesterol (p < 0.05). Further comparison of therapy-related differences between groups showed that the LT4 treatment was better in reducing UAER, low-density lipoprotein cholesterol and uric acid than the placebo group (p < 0.01 for all). The LT4 treatment may decrease UAER and exert kidney protection effects in early type 2 DN and SCH patients with mildly increased TSH levels and serum TPO-Ab positivity. However, due to the short duration of follow-up and small number of cases, the results of this study need future trials with larger numbers of patients and longer follow-up periods to verify whether such a strategy can provide durable benefits.

  16. Effects of a platelet gel on early graft revascularization after anterior cruciate ligament reconstruction: a prospective, randomized, double-blind, clinical trial.

    PubMed

    Vogrin, M; Rupreht, M; Dinevski, D; Hašpl, M; Kuhta, M; Jevsek, M; Knežević, M; Rožman, P

    2010-01-01

    Slow graft healing in bone tunnels and a slow graft ligamentization process after anterior cruciate ligament (ACL) reconstruction are some of the reasons for prolonged rehabilitation. The purpose of this study was to determine if the use of platelet gel (PG) accelerates early graft revascularization after ACL reconstruction. PG was produced from autologous platelet-rich plasma and applied locally. We quantitatively evaluated the revascularization process in the osteoligamentous interface zone in the bone tunnels and in the intra-articular part of the graft by means of contrast-enhanced magnetic resonance imaging (MRI). After 4-6 weeks, the PG-treated group demonstrated a significantly higher level of vascularization in the osteoligamentous interface (0.33 ± 0.09) than the control group (0.16 ± 0.09, p < 0.001). In the intra-articular part of the graft, we found no evidence of revascularization in either group. Locally applied PG enhanced early revascularization of the graft in the osteoligamentous interface zone after ACL reconstruction. Copyright © 2010 S. Karger AG, Basel.

  17. Connectivity Reveals Sources of Predictive Coding Signals in Early Visual Cortex During Processing of Visual Optic Flow.

    PubMed

    Schindler, Andreas; Bartels, Andreas

    2017-05-01

    Superimposed on the visual feed-forward pathway, feedback connections convey higher level information to cortical areas lower in the hierarchy. A prominent framework for these connections is the theory of predictive coding where high-level areas send stimulus interpretations to lower level areas that compare them with sensory input. Along these lines, a growing body of neuroimaging studies shows that predictable stimuli lead to reduced blood oxygen level-dependent (BOLD) responses compared with matched nonpredictable counterparts, especially in early visual cortex (EVC) including areas V1-V3. The sources of these modulatory feedback signals are largely unknown. Here, we re-examined the robust finding of relative BOLD suppression in EVC evident during processing of coherent compared with random motion. Using functional connectivity analysis, we show an optic flow-dependent increase of functional connectivity between BOLD suppressed EVC and a network of visual motion areas including MST, V3A, V6, the cingulate sulcus visual area (CSv), and precuneus (Pc). Connectivity decreased between EVC and 2 areas known to encode heading direction: entorhinal cortex (EC) and retrosplenial cortex (RSC). Our results provide first evidence that BOLD suppression in EVC for predictable stimuli is indeed mediated by specific high-level areas, in accord with the theory of predictive coding. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Microscopy reveals disease control through novel effects on fungal development: a case study with an early-generation benzophenone fungicide.

    PubMed

    Schmitt, Mark R; Carzaniga, Raffaella; Cotter, H Van T; O'Connell, Richard; Hollomon, Derek

    2006-05-01

    The benzophenones are a new class of agricultural fungicides that demonstrate protectant, curative and eradicative/antisporulant activity against powdery mildews. The chemistry is represented in the marketplace by the fungicide metrafenone, recently introduced by BASF and discussed in the following paper. The benzophenones show no evidence of acting by previously identified biochemical mechanisms, nor do they show cross-resistance with existing fungicides. The value of microscopy in elucidating fungicide mode of action is demonstrated through identification of the effects of an early benzophenone, eBZO, on mildew development. eBZO caused profound alterations in the morphology of powdery mildews of both monocotyledons and dicotyledons, affecting multiple stages of fungal development, including spore germination, appressorial formation, penetration, surface hyphal morphology and sporogenesis. Identification of analogous effects of eBZO on sporulation in the model organism Aspergillus nidulans (Eidam) Winter provides a unique opportunity to elucidate important morphogenetic regulatory sites in the economically important obligate pathogens, the powdery mildews. Benzophenones provide a further example of the benefits of whole-organism testing in the search for novel fungicide modes of action. Copyright 2006 Society of Chemical Industry.

  19. Exome capture sequencing reveals new insights into hepatitis B virus-induced hepatocellular carcinoma at the early stage of tumorigenesis.

    PubMed

    Chen, Yong; Wang, Lijuan; Xu, Hexiang; Liu, Xingxiang; Zhao, Yingren

    2013-10-01

    Hepatocellular carcinoma (HCC), the most common type of liver cancer, is the third primary cause of cancer-related mortality worldwide. The molecular mechanisms underlying the initiation and formation of HCC remain obscure. In the present study, we performed exome sequencing using tumor and normal tissues from 3 hepatitis B virus (HBV)-positive BCLC stage A HCC patients. Bioinformatic analysis was performed to find candidate protein-altering somatic mutations. Eighty damaging mutations were validated and 59 genes were reported to be mutated in HBV-related HCCs for the first time here. Further analysis using whole genome sequencing (WGS) data of 88 HBV-related HCC patients from the European Genome-phenome Archive database showed that mutations in 33 of the 59 genes were also detected in other samples. Variants of two newly found genes, ZNF717 and PARP4, were detected in more than 10% of the WGS samples. Several other genes, such as FLNA and CNTN2, are also noteworthy. Thus, the exome sequencing analysis of three BCLC stage A patients provides new insights into the molecular events governing the early steps of HBV-induced HCC tumorigenesis.

  20. Early stages of functional diversification in the Rab GTPase gene family revealed by genomic and localization studies in Paramecium species

    PubMed Central

    Bright, Lydia J.; Gout, Jean-Francois; Lynch, Michael

    2017-01-01

    New gene functions arise within existing gene families as a result of gene duplication and subsequent diversification. To gain insight into the steps that led to the functional diversification of paralogues, we tracked duplicate retention patterns, expression-level divergence, and subcellular markers of functional diversification in the Rab GTPase gene family in three Paramecium aurelia species. After whole-genome duplication, Rab GTPase duplicates are more highly retained than other genes in the genome but appear to be diverging more rapidly in expression levels, consistent with early steps in functional diversification. However, by localizing specific Rab proteins in Paramecium cells, we found that paralogues from the two most recent whole-genome duplications had virtually identical localization patterns, and that less closely related paralogues showed evidence of both conservation and diversification. The functionally conserved paralogues appear to target to compartments associated with both endocytic and phagocytic recycling functions, confirming evolutionary and functional links between the two pathways in a divergent eukaryotic lineage. Because the functionally diversifying paralogues are still closely related to and derived from a clade of functionally conserved Rab11 genes, we were able to pinpoint three specific amino acid residues that may be driving the change in the localization and thus the function in these proteins. PMID:28251922

  1. Horizontal Transfers and Gene Losses in the Phospholipid Pathway of Bartonella Reveal Clues about Early Ecological Niches

    PubMed Central

    Zhu, Qiyun; Kosoy, Michael; Olival, Kevin J.; Dittmar, Katharina

    2014-01-01

    Bartonellae are mammalian pathogens vectored by blood-feeding arthropods. Although of increasing medical importance, little is known about their ecological past, and host associations are underexplored. Previous studies suggest an influence of horizontal gene transfers in ecological niche colonization by acquisition of host pathogenicity genes. We here expand these analyses to metabolic pathways of 28 Bartonella genomes, and experimentally explore the distribution of bartonellae in 21 species of blood-feeding arthropods. Across genomes, repeated gene losses and horizontal gains in the phospholipid pathway were found. The evolutionary timing of these patterns suggests functional consequences likely leading to an early intracellular lifestyle for stem bartonellae. Comparative phylogenomic analyses discover three independent lineage-specific reacquisitions of a core metabolic gene—NAD(P)H-dependent glycerol-3-phosphate dehydrogenase (gpsA)—from Gammaproteobacteria and Epsilonproteobacteria. Transferred genes are significantly closely related to invertebrate Arsenophonus-, and Serratia-like endosymbionts, and mammalian Helicobacter-like pathogens, supporting a cellular association with arthropods and mammals at the base of extant Bartonella spp. Our studies suggest that the horizontal reacquisitions had a key impact on bartonellae lineage specific ecological and functional evolution. PMID:25106622

  2. Knockdown of Fanconi anemia genes in human embryonic stem cells reveals early developmental defects in the hematopoietic lineage.

    PubMed

    Tulpule, Asmin; Lensch, M William; Miller, Justine D; Austin, Karyn; D'Andrea, Alan; Schlaeger, Thorsten M; Shimamura, Akiko; Daley, George Q

    2010-04-29

    Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies. The effect of FA gene deficiency on hematopoietic development in utero remains poorly described as mouse models of FA do not develop hematopoietic failure and such studies cannot be performed on patients. We have created a human-specific in vitro system to study early hematopoietic development in FA using a lentiviral RNA interference (RNAi) strategy in human embryonic stem cells (hESCs). We show that knockdown of FANCA and FANCD2 in hESCs leads to a reduction in hematopoietic fates and progenitor numbers that can be rescued by FA gene complementation. Our data indicate that hematopoiesis is impaired in FA from the earliest stages of development, suggesting that deficiencies in embryonic hematopoiesis may underlie the progression to bone marrow failure in FA. This work illustrates how hESCs can provide unique insights into human development and further our understanding of genetic disease.

  3. 7T T₂*-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer's disease.

    PubMed

    van Rooden, Sanneke; Doan, Nhat Trung; Versluis, Maarten J; Goos, Jeroen D C; Webb, Andrew G; Oleksik, Ania M; van der Flier, Wiesje M; Scheltens, Philip; Barkhof, Frederik; Weverling-Rynsburger, Annelies W E; Blauw, Gerard Jan; Reiber, Johan H C; van Buchem, Mark A; Milles, Julien; van der Grond, Jeroen

    2015-01-01

    The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of Alzheimer's disease pathology, between early- and late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T magnetic resonance phase images. High-resolution T2(∗)-weighted scans were acquired in 12 EOAD patients and 17 LOAD patients with mild to moderate disease and 27 healthy elderly control subjects. Lobar peak-to-peak phase shifts and regional mean phase contrasts were computed. An increased peak-to-peak phase shift was found for all lobar regions in EOAD patients compared with LOAD patients (p < 0.05). Regional mean phase contrast in EOAD patients was higher than in LOAD patients in the superior medial and middle frontal gyrus, anterior and middle cingulate gyrus, postcentral gyrus, superior and inferior parietal gyrus, and precuneus (p ≤ 0.042). These data suggest that EOAD patients have an increased iron accumulation, possibly related to an increased amyloid deposition, in specific cortical regions as compared with LOAD patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression

    DOE PAGES

    Liu, Chih-Wei; Bramer, Lisa; Webb-Robertson, Bobbie-Jo; ...

    2017-10-07

    We report that blood markers other than islet autoantibodies are greatly needed to indicate the pancreatic beta cell destruction process as early as possible, and more accurately reflect the progression of Type 1 Diabetes Mellitus (T1D). To this end, a longitudinal proteomic profiling of human plasma using TMT-10plex-based LC-MS/MS analysis was performed to track temporal proteomic changes of T1D patients (n = 11) across 9 serial time points, spanning the period of T1D natural progression, in comparison with those of the matching healthy controls (n = 10). To our knowledge, the current study represents the largest (> 2000 proteins measured)more » longitudinal expression profiles of human plasma proteome in T1D research. By applying statistical trend analysis on the temporal expression patterns between T1D and controls, and Benjamini-Hochberg procedure for multiple-testing correction, 13 protein groups were regarded as having statistically significant differences during the entire follow-up period. Moreover, 16 protein groups, which play pivotal roles in response to oxidative stress, have consistently abnormal expression trend before seroconversion to islet autoimmunity. Importantly, the expression trends of two key reactive oxygen species-decomposing enzymes, Catalase and Superoxide dismutase were verified independently by ELISA.« less

  5. Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression

    SciTech Connect

    Liu, Chih-Wei; Bramer, Lisa; Webb-Robertson, Bobbie-Jo

    We report that blood markers other than islet autoantibodies are greatly needed to indicate the pancreatic beta cell destruction process as early as possible, and more accurately reflect the progression of Type 1 Diabetes Mellitus (T1D). To this end, a longitudinal proteomic profiling of human plasma using TMT-10plex-based LC-MS/MS analysis was performed to track temporal proteomic changes of T1D patients (n = 11) across 9 serial time points, spanning the period of T1D natural progression, in comparison with those of the matching healthy controls (n = 10). To our knowledge, the current study represents the largest (> 2000 proteins measured)more » longitudinal expression profiles of human plasma proteome in T1D research. By applying statistical trend analysis on the temporal expression patterns between T1D and controls, and Benjamini-Hochberg procedure for multiple-testing correction, 13 protein groups were regarded as having statistically significant differences during the entire follow-up period. Moreover, 16 protein groups, which play pivotal roles in response to oxidative stress, have consistently abnormal expression trend before seroconversion to islet autoimmunity. Importantly, the expression trends of two key reactive oxygen species-decomposing enzymes, Catalase and Superoxide dismutase were verified independently by ELISA.« less

  6. The First Molecular Phylogeny of Strepsiptera (Insecta) Reveals an Early Burst of Molecular Evolution Correlated with the Transition to Endoparasitism

    PubMed Central

    McMahon, Dino P.; Hayward, Alexander; Kathirithamby, Jeyaraney

    2011-01-01

    A comprehensive model of evolution requires an understanding of the relationship between selection at the molecular and phenotypic level. We investigate this in Strepsiptera, an order of endoparasitic insects whose evolutionary biology is poorly studied. We present the first molecular phylogeny of Strepsiptera, and use this as a framework to investigate the association between parasitism and molecular evolution. We find evidence of a significant burst in the rate of molecular evolution in the early history of Strepsiptera. The evolution of morphological traits linked to parasitism is significantly correlated with the pattern in molecular rate. The correlated burst in genotypic-phenotypic evolution precedes the main phase of strepsipteran diversification, which is characterised by the return to a low and even molecular rate, and a period of relative morphological stability. These findings suggest that the transition to endoparasitism led to relaxation of selective constraint in the strepsipteran genome. Our results indicate that a parasitic lifestyle can affect the rate of molecular evolution, although other causal life-history traits correlated with parasitism may also play an important role. PMID:21738621

  7. Enhancer and Transcription Factor Dynamics during Myeloid Differentiation Reveal an Early Differentiation Block in Cebpa null Progenitors.

    PubMed

    Pundhir, Sachin; Bratt Lauridsen, Felicia Kathrine; Schuster, Mikkel Bruhn; Jakobsen, Janus Schou; Ge, Ying; Schoof, Erwin Marten; Rapin, Nicolas; Waage, Johannes; Hasemann, Marie Sigurd; Porse, Bo Torben

    2018-05-29

    Transcription factors PU.1 and CEBPA are required for the proper coordination of enhancer activity during granulocytic-monocytic (GM) lineage differentiation to form myeloid cells. However, precisely how these factors control the chronology of enhancer establishment during differentiation is not known. Through integrated analyses of enhancer dynamics, transcription factor binding, and proximal gene expression during successive stages of murine GM-lineage differentiation, we unravel the distinct kinetics by which PU.1 and CEBPA coordinate GM enhancer activity. We find no evidence of a pioneering function of PU.1 during late GM-lineage differentiation. Instead, we delineate a set of enhancers that gain accessibility in a CEBPA-dependent manner, suggesting a pioneering function of CEBPA. Analyses of Cebpa null bone marrow demonstrate that CEBPA controls PU.1 levels and, unexpectedly, that the loss of CEBPA results in an early differentiation block. Taken together, our data provide insights into how PU.1 and CEBPA functionally interact to drive GM-lineage differentiation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Front blind spot crashes in Hong Kong.

    PubMed

    Cheng, Yuk Ki; Wong, Koon Hung; Tao, Chi Hang; Tam, Cheok Ning; Tam, Yiu Yan; Tsang, Cheuk Nam

    2016-09-01

    In 2012-2014, our laboratory had investigated a total of 9 suspected front blind spot crashes, in which the medium and heavy goods vehicles pulled away from rest and rolled over the pedestrians, who were crossing immediately in front of the vehicles. The drivers alleged that they did not see any pedestrians through the windscreens or the front blind spot mirrors. Forensic assessment of the goods vehicles revealed the existence of front blind spot zones in 3 out of these 9 accident vehicles, which were attributed to the poor mirror adjustments or even the absence of a front blind spot mirror altogether. In view of this, a small survey was devised involving 20 randomly selected volunteers and their goods vehicles and 5 out of these vehicles had blind spots at the front. Additionally, a short questionnaire was conducted on these 20 professional lorry drivers and it was shown that most of them were not aware of the hazards of blind spots immediately in front of their vehicles, and many did not use the front blind spot mirrors properly. A simple procedure for quick measurements of the coverage of front blind spot mirrors using a coloured plastic mat with dimensional grids was also introduced and described in this paper. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Global data on blindness.

    PubMed Central

    Thylefors, B.; Négrel, A. D.; Pararajasegaram, R.; Dadzie, K. Y.

    1995-01-01

    Globally, it is estimated that there are 38 million persons who are blind. Moreover, a further 110 million people have low vision and are at great risk of becoming blind. The main causes of blindness and low vision are cataract, trachoma, glaucoma, onchocerciasis, and xerophthalmia; however, insufficient data on blindness from causes such as diabetic retinopathy and age-related macular degeneration preclude specific estimations of their global prevalence. The age-specific prevalences of the major causes of blindness that are related to age indicate that the trend will be for an increase in such blindness over the decades to come, unless energetic efforts are made to tackle these problems. More data collected through standardized methodologies, using internationally accepted (ICD-10) definitions, are needed. Data on the incidence of blindness due to common causes would be useful for calculating future trends more precisely. PMID:7704921

  10. Efficacy of early neonatal supplementation with vitamin A to reduce mortality in infancy in Haryana, India (Neovita): a randomised, double-blind, placebo-controlled trial.

    PubMed

    Mazumder, Sarmila; Taneja, Sunita; Bhatia, Kiran; Yoshida, Sachiyo; Kaur, Jasmine; Dube, Brinda; Toteja, G S; Bahl, Rajiv; Fontaine, Olivier; Martines, Jose; Bhandari, Nita

    2015-04-04

    Vitamin A supplementation in children aged 6 months to 5 years has been shown to reduce mortality. The efficacy of neonatal supplementation with vitamin A to reduce mortality in the first 6 months of life is plausible but not established. We aimed to assess the efficacy of neonatal oral supplementation with vitamin A to reduce mortality between supplementation and 6 months of age. We undertook an individually randomised, double-blind, placebo-controlled trial in Haryana, India. We identified pregnant women through a surveillance programme undertaken every 3 months of all female residents in two districts of Haryana, India, aged 15-49 years, and screened every identified livebirth. Eligible participants were neonates whose parents consented to participate, were likely to stay in the study area until at least 6 months of age, and were able to feed orally at the time of enrolment. Participants were randomly assigned to receive oral capsules containing vitamin A (retinol palmitate 50,000 IU plus vitamin E 9·5-12·6 IU) or placebo (vitamin E 9·5-12·6 IU) within 72 h of birth. Randomisation was in blocks of 20 according to a randomisation list prepared by a statistician not otherwise involved with the trial. Investigators, participants' families, and the data analysis team were masked to treatment allocation. The primary outcome was mortality between supplementation and 6 months of age. Analysis included all participants assigned to study groups. This trial is registered with ClinicalTrials.gov, number NCT01138449, and the Indian Council of Medical Research Clinical Trial Registry, number CTRI/2010/091/000220. Between June 24, 2010, and July 1, 2012 we screened 47,777 neonates and randomly assigned 44,984 to receive vitamin A (22,493) or placebo (22,491). Between supplementation and 6 months of age, 656 infants died in the vitamin A group compared with 726 in the placebo group (29·2 per 1000 vs 32·3 per 1000; difference -3·1 per 1000, 95% CI -6·3 to 0·1; risk

  11. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial.

    PubMed

    Baud, Olivier; Maury, Laure; Lebail, Florence; Ramful, Duksha; El Moussawi, Fatima; Nicaise, Claire; Zupan-Simunek, Véronique; Coursol, Anne; Beuchée, Alain; Bolot, Pascal; Andrini, Pierre; Mohamed, Damir; Alberti, Corinne

    2016-04-30

    Bronchopulmonary dysplasia, a major complication of extreme prematurity, has few treatment options. Postnatal steroid use is controversial, but low-dose hydrocortisone might prevent the harmful effects of inflammation on the developing lung. In this study, we aimed to assess whether low-dose hydrocortisone improved survival without bronchopulmonary dysplasia in extremely preterm infants. In this double-blind, placebo-controlled, randomised trial done at 21 French tertiary-care neonatal intensive care units (NICUs), we randomly assigned (1:1), via a secure study website, extremely preterm infants inborn (born in a maternity ward at the same site as the NICU) at less than 28 weeks of gestation to receive either intravenous low-dose hydrocortisone or placebo during the first 10 postnatal days. Infants randomly assigned to the hydrocortisone group received 1 mg/kg of hydrocortisone hemisuccinate per day divided into two doses per day for 7 days, followed by one dose of 0·5 mg/kg per day for 3 days. Randomisation was stratified by gestational age and all infants were enrolled by 24 h after birth. Study investigators, parents, and patients were masked to treatment allocation. The primary outcome was survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age. We used a sequential analytical design, based on intention to treat, to avoid prolonging the trial after either efficacy or futility had been established. This trial is registered with ClinicalTrial.gov, number NCT00623740. 1072 neonates were screened between May 25, 2008, and Jan 31, 2014, of which 523 were randomly assigned (256 hydrocortisone, 267 placebo). 255 infants on hydrocortisone and 266 on placebo were included in analyses after parents withdrew consent for one child in each group. Of the 255 infants assigned to hydrocortisone, 153 (60%) survived without bronchopulmonary dysplasia, compared with 136 (51%) of 266 infants assigned to placebo (odds ratio [OR] adjusted for gestational age

  12. Early stages of functional diversification in the Rab GTPase gene family revealed by genomic and localization studies in Paramecium species.

    PubMed

    Bright, Lydia J; Gout, Jean-Francois; Lynch, Michael

    2017-04-15

    New gene functions arise within existing gene families as a result of gene duplication and subsequent diversification. To gain insight into the steps that led to the functional diversification of paralogues, we tracked duplicate retention patterns, expression-level divergence, and subcellular markers of functional diversification in the Rab GTPase gene family in three Paramecium aurelia species. After whole-genome duplication, Rab GTPase duplicates are more highly retained than other genes in the genome but appear to be diverging more rapidly in expression levels, consistent with early steps in functional diversification. However, by localizing specific Rab proteins in Paramecium cells, we found that paralogues from the two most recent whole-genome duplications had virtually identical localization patterns, and that less closely related paralogues showed evidence of both conservation and diversification. The functionally conserved paralogues appear to target to compartments associated with both endocytic and phagocytic recycling functions, confirming evolutionary and functional links between the two pathways in a divergent eukaryotic lineage. Because the functionally diversifying paralogues are still closely related to and derived from a clade of functionally conserved Rab11 genes, we were able to pinpoint three specific amino acid residues that may be driving the change in the localization and thus the function in these proteins. © 2017 Bright et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  13. MOLECULAR IMAGING REVEALS RAPID REDUCTION OF ENDOTHELIAL ACTIVATION IN EARLY ATHEROSCLEROSIS WITH APOCYNIN INDEPENDENT OF ANTI-OXIDATIVE PROPERTIES

    PubMed Central

    Khanicheh, Elham; Qi, Yue; Xie, Aris; Mitterhuber, Martina; Xu, Lifen; Mochizuki, Michika; Daali, Youssef; Jaquet, Vincent; Krause, Karl-Heinz; Ruggeri, Zaverio M.; Kuster, Gabriela M.; Lindner, Jonathan R.; Kaufmann, Beat A.

    2013-01-01

    OBJECTIVE Anti-oxidative drugs continue to be developed for the treatment of atherosclerosis. Apocynin is an NADPH-oxidase-inhibitor with anti-inflammatory properties. We used contrast enhanced ultrasound (CEU) molecular imaging to assess whether short-term apocynin therapy in atherosclerosis reduces vascular oxidative stress and endothelial activation APPROACH AND RESULTS Genetically-modified mice with early atherosclerosis were studied at baseline and after 7 days of therapy with apocynin (4mg/kg/d I.P.) or saline. CEU molecular imaging of the aorta was performed with microbubbles targeted to vascular cell adhesion molecule 1 (VCAM-1; MBV), to platelet GPIbα (MBPl), and control microbubbles (MBCtr). Aortic VCAM-1 was measured using Western Blot. Aortic ROS generation was measured using a lucigenin assay. Hydroethidine (HE) oxidation was used to assess aortic superoxide generation. Baseline signal for MBV (1.3±0.3 A.U.) and MBPl (1.5±0.5 A.U.) was higher than for MBCtr (0.5±0.2 A.U., p<0.01). In saline-treated animals, signal did not significantly change for any microbubble agent whereas short-term apocynin significantly (p<0.05) reduced VCAM-1 and platelet signal (MBV: 0.3±0.1, MBPl: 0.4±0.1 MBCtr: 0.3±0.2 A.U., p=0.6 between agents). Apocynin reduced aortic VCAM-1 expression by 50% (p<0.05). However, apocynin therapy did not reduce either ROS content, superoxide generation, or macrophage content. CONCLUSIONS Short-term treatment with apocynin in atherosclerosis reduces endothelial cell adhesion molecule expression. This change in endothelial phenotype can be detected by molecular imaging before any measurable decrease in macrophage content, and is not associated with a detectable change in oxidative burden. PMID:23908248

  14. Deep Sequencing of the Medicago truncatula Root Transcriptome Reveals a Massive and Early Interaction between Nodulation Factor and Ethylene Signals.

    PubMed

    Larrainzar, Estíbaliz; Riely, Brendan K; Kim, Sang Cheol; Carrasquilla-Garcia, Noelia; Yu, Hee-Ju; Hwang, Hyun-Ju; Oh, Mijin; Kim, Goon Bo; Surendrarao, Anandkumar K; Chasman, Deborah; Siahpirani, Alireza F; Penmetsa, Ramachandra V; Lee, Gang-Seob; Kim, Namshin; Roy, Sushmita; Mun, Jeong-Hwan; Cook, Douglas R

    2015-09-01

    The legume-rhizobium symbiosis is initiated through the activation of the Nodulation (Nod) factor-signaling cascade, leading to a rapid reprogramming of host cell developmental pathways. In this work, we combine transcriptome sequencing with molecular genetics and network analysis to quantify and categorize the transcriptional changes occurring in roots of Medicago truncatula from minutes to days after inoculation with Sinorhizobium medicae. To identify the nature of the inductive and regulatory cues, we employed mutants with absent or decreased Nod factor sensitivities (i.e. Nodulation factor perception and Lysine motif domain-containing receptor-like kinase3, respectively) and an ethylene (ET)-insensitive, Nod factor-hypersensitive mutant (sickle). This unique data set encompasses nine time points, allowing observation of the symbiotic regulation of diverse biological processes with high temporal resolution. Among the many outputs of the study is the early Nod factor-induced, ET-regulated expression of ET signaling and biosynthesis genes. Coupled with the observation of massive transcriptional derepression in the ET-insensitive background, these results suggest that Nod factor signaling activates ET production to attenuate its own signal. Promoter:β-glucuronidase fusions report ET biosynthesis both in root hairs responding to rhizobium as well as in meristematic tissue during nodule organogenesis and growth, indicating that ET signaling functions at multiple developmental stages during symbiosis. In addition, we identified thousands of novel candidate genes undergoing Nod factor-dependent, ET-regulated expression. We leveraged the power of this large data set to model Nod factor- and ET-regulated signaling networks using MERLIN, a regulatory network inference algorithm. These analyses predict key nodes regulating the biological process impacted by Nod factor perception. We have made these results available to the research community through a searchable online

  15. The effect of early trauma exposure on serotonin type 1B receptor expression revealed by reduced selective radioligand binding.

    PubMed

    Murrough, James W; Czermak, Christoph; Henry, Shannan; Nabulsi, Nabeel; Gallezot, Jean-Dominique; Gueorguieva, Ralitza; Planeta-Wilson, Beata; Krystal, John H; Neumaier, John F; Huang, Yiyun; Ding, Yu-Shin; Carson, Richard E; Neumeister, Alexander

    2011-09-01

    Serotonergic dysfunction is implicated in the pathogenesis of posttraumatic stress disorder (PTSD), and recent animal models suggest that disturbances in serotonin type 1B receptor function, in particular, may contribute to chronic anxiety. However, the specific role of the serotonin type 1B receptor has not been studied in patients with PTSD. To investigate in vivo serotonin type 1B receptor expression in individuals with PTSD, trauma-exposed control participants without PTSD (TC), and healthy (non-trauma-exposed) control participants (HC) using positron emission tomography and the recently developed serotonin type 1B receptor selective radiotracer [(11)C]P943. Cross-sectional positron emission tomography study under resting conditions. Academic and Veterans Affairs medical centers. Ninety-six individuals in 3 study groups: PTSD (n = 49), TC (n = 20), and HC (n = 27). Main Outcome Measure  Regional [(11)C]P943 binding potential (BP(ND)) values in an a priori-defined limbic corticostriatal circuit investigated using multivariate analysis of variance and multiple regression analysis. A history of severe trauma exposure in the PTSD and TC groups was associated with marked reductions in [(11)C]P943 BP(ND) in the caudate, the amygdala, and the anterior cingulate cortex. Participant age at first trauma exposure was strongly associated with low [(11)C]P943 BP(ND). Developmentally earlier trauma exposure also was associated with greater PTSD symptom severity and major depression comorbidity. These data suggest an enduring effect of trauma history on brain function and the phenotype of PTSD. The association of early age at first trauma and more pronounced neurobiological and behavioral alterations in PTSD suggests a developmental component in the cause of PTSD.

  16. Immediate early gene expression reveals interactions between social and nicotine rewards on brain activity in adolescent male rats

    PubMed Central

    Goenaga, Julianna; Hatch, Kayla N.; Henricks, Angela; Scott, Samantha; Hood, Lauren E.; Neisewander, Janet L.

    2016-01-01

    Smoking initiation predominantly occurs during adolescence, often in the presence of peers. Therefore, understanding the neural mechanisms underlying the rewarding effects of nicotine and social stimuli is vital. Using the conditioned place preference (CPP) procedure, we measured immediate early gene (IEG) expression in animals following exposure either to a reward-conditioned environment or to the unconditioned stimuli (US). Adolescent, male rats were assigned to the following CPP US conditions: (1) Saline + Isolated, (2) Nicotine + Isolated, (3) Saline + Social, or (4) Nicotine + Social. For Experiment 1, brain tissue was collected 90 min following the CPP expression test and processed for Fos immunohistochemistry. We found that rats conditioned with nicotine with or without a social partner exhibited CPP; however, we found no group differences in Fos expression in any brain region analyzed, with the exception of the nucleus accumbens core that exhibited a social-induced attenuation in Fos expression. For Experiment 2, brain tissue was collected 90 min following US exposure during the last conditioning session. We found social reward-induced increases in IEG expression in striatal and amydalar subregions. In contrast, nicotine reduced IEG expression in prefrontal and striatal subregions. Reward interactions were also found in the dorsolateral striatum, basolateral amygdala, and ventral tegmental area where nicotine alone attenuated IEG expression and social reward reversed this effect. These results suggest that in general social rewards enhance, whereas nicotine attenuates, activation of mesocorticolimbic regions; however, the rewards given together interact to enhance activation in some regions. The findings contribute to knowledge of how a social environment influences nicotine effects. PMID:27435419

  17. Immediate early gene expression reveals interactions between social and nicotine rewards on brain activity in adolescent male rats.

    PubMed

    Bastle, Ryan M; Peartree, Natalie A; Goenaga, Julianna; Hatch, Kayla N; Henricks, Angela; Scott, Samantha; Hood, Lauren E; Neisewander, Janet L

    2016-10-15

    Smoking initiation predominantly occurs during adolescence, often in the presence of peers. Therefore, understanding the neural mechanisms underlying the rewarding effects of nicotine and social stimuli is vital. Using the conditioned place preference (CPP) procedure, we measured immediate early gene (IEG) expression in animals following exposure either to a reward-conditioned environment or to the unconditioned stimuli (US). Adolescent, male rats were assigned to the following CPP US conditions: (1) Saline+Isolated, (2) Nicotine+Isolated, (3) Saline+Social, or (4) Nicotine+Social. For Experiment 1, brain tissue was collected 90min following the CPP expression test and processed for Fos immunohistochemistry. We found that rats conditioned with nicotine with or without a social partner exhibited CPP; however, we found no group differences in Fos expression in any brain region analyzed, with the exception of the nucleus accumbens core that exhibited a social-induced attenuation in Fos expression. For Experiment 2, brain tissue was collected 90min following US exposure during the last conditioning session. We found social reward-induced increases in IEG expression in striatal and amydalar subregions. In contrast, nicotine reduced IEG expression in prefrontal and striatal subregions. Reward interactions were also found in the dorsolateral striatum, basolateral amygdala, and ventral tegmental area where nicotine alone attenuated IEG expression and social reward reversed this effect. These results suggest that in general social rewards enhance, whereas nicotine attenuates, activation of mesocorticolimbic regions; however, the rewards given together interact to enhance activation in some regions. The findings contribute to knowledge of how a social environment influences nicotine effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. The effect of a single infusion of zoledronic acid on early implant migration in total hip arthroplasty. A randomized, double-blind, controlled trial.

    PubMed

    Friedl, Gerald; Radl, Roman; Stihsen, Christoph; Rehak, Peter; Aigner, Reingard; Windhager, Reinhard

    2009-02-01

    Aseptic loosening is the most frequent cause of implant failure in total hip arthroplasty. While a direct link between aseptic loosening and periprosthetic bone loss remains elusive, there is plentiful evidence for a close association with early implant migration. The present trial was primarily designed to evaluate whether a single infusion of 4 mg of zoledronic acid prevented early implant migration in patients with osteonecrosis of the femoral head. Fifty patients were consecutively enrolled to receive either zoledronic acid or saline solution after cementless total hip arthroplasty. Radiographs, biochemical parameters of bone turnover, and the Harris hip-rating score were determined preoperatively and at each follow-up examination at seven weeks, six months, one year, and yearly thereafter. The median follow-up period was 2.8 years. We found a significant subsidence of the stem of up to a mean (and standard deviation) of -1.2 +/- 0.6 mm at two years within the control group, and the cups had a mean medialization of 0.6 +/- 1.0 mm and a mean cranialization of 0.6 +/- 0.8 mm (p < 0.001). Treatment with zoledronic acid effectively minimized the migration of the cups in both the transverse and the vertical direction (mean, 0.15 +/- 0.6 mm and 0.06 +/- 0.6 mm, respectively; p < 0.05), while only a trend to decreased subsidence of the stem was detected. Finally, the Harris hip score rapidly increased over time in both treatment groups, although this increase was significantly more pronounced in the zoledronate-treated group than in the control group (analysis of variance, p = 0.008). A single infusion of zoledronic acid shows promise in improving initial fixation of a cementless implant, which may improve the clinical outcome of total hip arthroplasty in patients with osteonecrosis of the femoral head.

  19. Comparison of spatula and cytobrush cytological techniques in early detection of oral malignant and premalignant lesions: a prospective and blinded study.

    PubMed

    Nanayakkara, P G C L; Dissanayaka, W L; Nanayakkara, B G; Amaratunga, E A P D; Tilakaratne, W M

    2016-04-01

    The use of oral cytology to diagnose malignant and premalignant lesions at an early stage is considered crucial. The aim of this study was to evaluate the diagnoses of the spatula and the cytobrush techniques compared with the gold standard histopathological findings, analysed according to different diagnostic criteria. Cytological smears were obtained from 76 suspicious oral malignant lesions and 116 oral leukoplakia lesions using two techniques: cytobrush plus cell collector and metal spatula. Subsequently, a surgical biopsy was performed on each lesion to achieve a histopathological diagnosis. Evaluation was conducted with respect to three different diagnostic criteria. The sensitivity for diagnosing carcinoma in clinically malignant cases was 89.58% and 60.42% for cytobrush and spatula techniques, respectively. Inclusion of severe dysplastic cases for 'high-risk' lesions increased the sensitivity up to 96.36% and 78.18% for two techniques, respectively. In leukoplakia lesions, malignant and severely dysplastic cells were diagnosed at a sensitivity of 88.89% in the cytobrush and 55.56% in the spatula techniques. Extending the criteria by defining malignant or any dysplastic findings as positive, sensitivity was increased to 98.02% and 89.11% for the spatula and the cytobrush techniques, respectively. Specificity for both techniques increased to 100%. The difference between the diagnoses of histopathology and the spatula cytology was statistically significant (P < 0.01), while no such difference was found with the cytobrush technique (P > 0.1). The cytobrush, unlike the spatula, is a useful screening instrument for early diagnosis of suspicious oral lesions and could therefore contribute to improved oral cancer prognosis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. A model of early human embryonic stem cell differentiation reveals inter- and intracellular changes on transition to squamous epithelium.

    PubMed

    Galat, Vasiliy; Malchenko, Sergey; Galat, Yekaterina; Ishkin, Alex; Nikolsky, Yuri; Kosak, Steven T; Soares, Bento Marcelo; Iannaccone, Philip; Crispino, John D; Hendrix, Mary J C

    2012-05-20

    The molecular events leading to human embryonic stem cell (hESC) differentiation are the subject of considerable scrutiny. Here, we characterize an in vitro model that permits analysis of the earliest steps in the transition of hESC colonies to squamous epithelium on basic fibroblast growth factor withdrawal. A set of markers (GSC, CK18, Gata4, Eomes, and Sox17) point to a mesendodermal nature of the epithelial cells with subsequent commitment to definitive endoderm (Sox17, Cdx2, nestin, and Islet1). We assayed alterations in the transcriptome in parallel with the distribution of immunohistochemical markers. Our results indicate that the alterations of tight junctions in pluripotent culture precede the beginning of differentiation. We defined this cell population as "specified," as it is committed toward differentiation. The transitional zone between "specified" pluripotent and differentiated cells displays significant up-regulation of keratin-18 (CK18) along with a decrease in the functional activity of gap junctions and the down-regulation of 2 gap junction proteins, connexin 43 (Cx43) and connexin 45 (Cx45), which is coincidental with substantial elevation of intracellular Ca2+ levels. These findings reveal a set of cellular changes that may represent the earliest markers of in vitro hESC transition to an epithelial phenotype, before the induction of gene expression networks that guide hESC differentiation. Moreover, we hypothesize that these events may be common during the primary steps of hESC commitment to functionally varied epithelial tissue derivatives of different embryological origins.

  1. Environmental proteomics reveals early microbial community responses to biostimulation at a uranium- and nitrate-contaminated site.

    PubMed

    Chourey, Karuna; Nissen, Silke; Vishnivetskaya, Tatiana; Shah, Manesh; Pfiffner, Susan; Hettich, Robert L; Löffler, Frank E

    2013-10-01

    High-performance MS instrumentation coupled with improved protein extraction techniques enables metaproteomics to identify active members of soil and groundwater microbial communities. Metaproteomics workflows were applied to study the initial responses (i.e. 4 days post treatment) of the indigenous aquifer microbiota to biostimulation with emulsified vegetable oil (EVO) at a uranium-contaminated site. Members of the Betaproteobacteria (i.e. Dechloromonas, Ralstonia, Rhodoferax, Polaromonas, Delftia, Chromobacterium) and the Firmicutes dominated the biostimulated aquifer community. Proteome characterization revealed distinct differences between the microbial biomass collected from groundwater influenced by biostimulation and groundwater collected upgradient of the EVO injection points. In particular, proteins involved in ammonium assimilation, EVO degradation, and polyhydroxybutyrate granule formation were prominent following biostimulation. Interestingly, the atypical NosZ of Dechloromonas spp. was highly abundant, suggesting active nitrous oxide (N2 O) respiration. c-Type cytochromes were barely detected, as was citrate synthase, a biomarker for hexavalent uranium reduction activity, suggesting that uranium reduction has not commenced 4 days post EVO amendment. Environmental metaproteomics identified microbial community responses to biostimulation and elucidated active pathways demonstrating the value of this technique as a monitoring tool and for complementing nucleic acid-based approaches. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Environmental proteomics reveals early microbial community responses to biostimulation at a uranium- and nitrate-contaminated site

    SciTech Connect

    Chourey, Karuna; Nissen, Silke; Vishnivetskaya, T.

    2013-01-01

    High performance mass spectrometry instrumentation coupled with improved protein extraction techniques enable metaproteomics to identify active members of soil and groundwater microbial communities. Metaproteomics workflows were applied to study the initial responses (i.e., 4 days post treatment) of the indigenous aquifer microbiota to biostimulation with emulsified vegetable oil (EVO) at a uranium-contaminated site. Members of the Betaproteobacteria (i.e., Dechloromonas, Ralstonia, Rhodoferax, Polaromonas, Delftia, Chromobacterium) and Firmicutes dominated the biostimulated aquifer community. Proteome characterization revealed distinct differences in protein expression between the microbial biomass collected from groundwater influenced by biostimulation and groundwater collected up-gradient of the EVO injection points. In particular,more » proteins involved in ammonium assimilation, EVO degradation, and polyhydroxybutyrate (PHB) granule formation were prominent following biostimulation. Interestingly, the atypical NosZ of a Dechloromonas sp. was highly expressed suggesting active nitrous oxide (N2O) respiration. c-type cytochromes were barely detected, as was citrate synthase, a biomarker for hexavalent uranium reduction activity, suggesting that metal reduction has not commenced 4 days post EVO delivery. Environmental metaproteomics identified microbial community responses to biostimulation and elucidated active pathways demonstrating the value of this technique for complementing nucleic acid-based approaches.« less

  3. Aeromagnetic anomalies reveal the link between magmatism and tectonics during the early formation of the Canary Islands.

    PubMed

    Blanco-Montenegro, Isabel; Montesinos, Fuensanta G; Arnoso, José

    2018-01-08

    The 3-D inverse modelling of a magnetic anomaly measured over the NW submarine edifice of the volcanic island of Gran Canaria revealed a large, reversely-magnetized, elongated structure following an ENE-WSW direction, which we interpreted as a sill-like magmatic intrusion emplaced during the submarine growth of this volcanic island, with a volume that could represent up to about 20% of the whole island. The elongated shape of this body suggests the existence of a major crustal fracture in the central part of the Canary Archipelago which would have favoured the rapid ascent and emplacement of magmas during a time span from 0.5 to 1.9 My during a reverse polarity chron of the Earth's magnetic field prior to 16 Ma. The agreement of our results with those of previous gravimetric, seismological and geodynamical studies strongly supports the idea that the genesis of the Canary Islands was conditioned by a strike-slip tectonic framework probably related to Atlas tectonic features in Africa. These results do not contradict the hotspot theory for the origin of the Canary magmatism, but they do introduce the essential role of regional crustal tectonics to explain where and how those magmas both reached the surface and built the volcanic edifices.

  4. Exome sequencing analysis reveals variants in primary immunodeficiency genes in patients with very early onset inflammatory bowel disease.

    PubMed

    Kelsen, Judith R; Dawany, Noor; Moran, Christopher J; Petersen, Britt-Sabina; Sarmady, Mahdi; Sasson, Ariella; Pauly-Hubbard, Helen; Martinez, Alejandro; Maurer, Kelly; Soong, Joanne; Rappaport, Eric; Franke, Andre; Keller, Andreas; Winter, Harland S; Mamula, Petar; Piccoli, David; Artis, David; Sonnenberg, Gregory F; Daly, Mark; Sullivan, Kathleen E; Baldassano, Robert N; Devoto, Marcella

    2015-11-01

    Very early onset inflammatory bowel disease (VEO-IBD), IBD diagnosed at 5 years of age or younger, frequently presents with a different and more severe phenotype than older-onset IBD. We investigated whether patients with VEO-IBD carry rare or novel variants in genes associated with immunodeficiencies that might contribute to disease development. Patients with VEO-IBD and parents (when available) were recruited from the Children's Hospital of Philadelphia from March 2013 through July 2014. We analyzed DNA from 125 patients with VEO-IBD (age, 3 wk to 4 y) and 19 parents, 4 of whom also had IBD. Exome capture was performed by Agilent SureSelect V4, and sequencing was performed using the Illumina HiSeq platform. Alignment to human genome GRCh37 was achieved followed by postprocessing and variant calling. After functional annotation, candidate variants were analyzed for change in protein function, minor allele frequency less than 0.1%, and scaled combined annotation-dependent depletion scores of 10 or less. We focused on genes associated with primary immunodeficiencies and related pathways. An additional 210 exome samples from patients with pediatric IBD (n = 45) or adult-onset Crohn's disease (n = 20) and healthy individuals (controls, n = 145) were obtained from the University of Kiel, Germany, and used as control groups. Four hundred genes and regions associated with primary immunodeficiency, covering approximately 6500 coding exons totaling more than 1 Mbp of coding sequence, were selected from the whole-exome data. Our analysis showed novel and rare variants within these genes that could contribute to the development of VEO-IBD, including rare heterozygous missense variants in IL10RA and previously unidentified variants in MSH5 and CD19. In an exome sequence analysis of patients with VEO-IBD and their parents, we identified variants in genes that regulate B- and T-cell functions and could contribute to pathogenesis. Our analysis could lead to the

  5. Early time excited-state structural evolution of pyranine in methanol revealed by femtosecond stimulated Raman spectroscopy.

    PubMed

    Wang, Yanli; Liu, Weimin; Tang, Longteng; Oscar, Breland; Han, Fangyuan; Fang, Chong

    2013-07-25

    To understand chemical reactivity of molecules in condensed phase in real time, a structural dynamics technique capable of monitoring molecular conformational motions on their intrinsic time scales, typically on femtoseconds to picoseconds, is needed. We have studied a strong photoacid pyranine (8-hydroxypyrene-1,3,6-trisulfonic acid, HPTS, pK(a)* ≈ 0) in pure methanol and observed that excited-state proton transfer (ESPT) is absent, in sharp contrast with our previous work on HPTS in aqueous solutions wherein ESPT prevails following photoexcitation. Two transient vibrational marker bands at ~1477 (1454) and 1532 (1528) cm(-1) appear in CH3OH (CD3OD), respectively, rising within the instrument response time of ~140 fs and decaying with 390-470 (490-1400) fs and ~200 ps time constants in CH3OH (CD3OD). We attribute the mode onset to small-scale coherent proton motion along the pre-existing H-bonding chain between HPTS and methanol, and the two decay stages to the low-frequency skeletal motion-modulated Franck-Condon relaxation within ~1 ps and subsequent rotational diffusion of H-bonding partners in solution before fluorescence. The early time kinetic isotope effect (KIE) of ~3 upon methanol deuteration argues active proton motions particularly within the first few picoseconds when coherent skeletal motions are underdamped. Pronounced quantum beats are observed for high-frequency modes consisting of strong phenolic COH rocking (1532 cm(-1)) or H-out-of-plane wagging motions (952 cm(-1)) due to anharmonic coupling to coherent low-frequency modes impulsively excited at ca. 96, 120, and 168 cm(-1). The vivid illustration of atomic motions of HPTS in varying H-bonding geometry with neighboring methanol molecules unravels the multidimensional energy relaxation pathways immediately following photoexcitation, and provides compelling evidence that, in lieu of ESPT, the photoacidity of HPTS promptly activates characteristic low-frequency skeletal motions to search phase

  6. A Model of Early Human Embryonic Stem Cell Differentiation Reveals Inter- and Intracellular Changes on Transition to Squamous Epithelium

    PubMed Central

    Malchenko, Sergey; Galat, Yekaterina; Ishkin, Alex; Nikolsky, Yuri; Kosak, Steven T.; Soares, Bento Marcelo; Iannaccone, Philip; Crispino, John D.; Hendrix, Mary J.C.

    2012-01-01

    The molecular events leading to human embryonic stem cell (hESC) differentiation are the subject of considerable scrutiny. Here, we characterize an in vitro model that permits analysis of the earliest steps in the transition of hESC colonies to squamous epithelium on basic fibroblast growth factor withdrawal. A set of markers (GSC, CK18, Gata4, Eomes, and Sox17) point to a mesendodermal nature of the epithelial cells with subsequent commitment to definitive endoderm (Sox17, Cdx2, nestin, and Islet1). We assayed alterations in the transcriptome in parallel with the distribution of immunohistochemical markers. Our results indicate that the alterations of tight junctions in pluripotent culture precede the beginning of differentiation. We defined this cell population as “specified,” as it is committed toward differentiation. The transitional zone between “specified” pluripotent and differentiated cells displays significant up-regulation of keratin-18 (CK18) along with a decrease in the functional activity of gap junctions and the down-regulation of 2 gap junction proteins, connexin 43 (Cx43) and connexin 45 (Cx45), which is coincidental with substantial elevation of intracellular Ca2+ levels. These findings reveal a set of cellular changes that may represent the earliest markers of in vitro hESC transition to an epithelial phenotype, before the induction of gene expression networks that guide hESC differentiation. Moreover, we hypothesize that these events may be common during the primary steps of hESC commitment to functionally varied epithelial tissue derivatives of different embryological origins. PMID:21861759

  7. Platelet Proteomic Analysis Revealed Differential Pattern of Cytoskeletal- and Immune-Related Proteins at Early Stages of Alzheimer's Disease.

    PubMed

    González-Sánchez, Marta; Díaz, Teresa; Pascual, Consuelo; Antequera, Desiree; Herrero-San Martín, Alejandro; Llamas-Velasco, Sara; Villarejo-Galende, Alberto; Bartolome, Fernando; Carro, Eva

    2018-03-30

    Platelets are considered a good model system to study a number of elements associated with neuronal pathways as they share biochemical similarities. Platelets represent the major source of amyloid-β (Aβ) in blood contributing to the Aβ accumulation in the brain parenchyma and vasculature. Peripheral blood platelet alterations including cytoskeletal abnormalities, abnormal cytoplasmic calcium fluxes or increased oxidative stress levels have been related to Alzheimer's disease (AD) pathology. Therefore, platelets can be considered a peripheral model to study metabolic mechanisms occurring in AD. To investigate peripheral molecular alterations, we examined platelet protein expression in a cohort of 164 subjects, including mild cognitive impairment (MCI), and AD patients, and healthy aged-matched controls. A two-dimensional difference gel electrophoresis (2D-DIGE) discovery phase revealed significant differences between patients and controls in five proteins: talin, vinculin, moesin, complement C3b and Rho GDP, which are known to be involved in cytoskeletal regulation including focal adhesions, inflammation and immune functions. Western blot analysis verified that talin was found to be increased in mild and moderate AD groups versus control, while the other three were found to be decreased. We also analysed amyloid precursor protein (APP), amyloid-β 1-40 (Aβ 40 ) and 1-42 (Aβ 42 ) levels in platelets from the same groups of subjects. Upregulation of platelet APP and Aβ peptides was found in AD patients compared to controls. These findings complement and expand previous reports concerning the morphological and functional alterations in AD platelets, and provide more insights into possible mechanisms that participate in the multifactorial and systemic damage in AD.

  8. Mechanisms for renal blood flow control early in diabetes as revealed by chronic flow measurement and transfer function analysis.

    PubMed

    Bell, Tracy D; DiBona, Gerald F; Wang, Ying; Brands, Michael W

    2006-08-01

    The purpose of this study was to establish the roles of the myogenic response and the TGF mechanism in renal blood flow (RBF) control at the very earliest stages of diabetes. Mean arterial pressure (MAP) and RBF were measured continuously, 18 h/d, in uninephrectomized control and diabetic rats, and transfer function analysis was used to determine the dynamic autoregulatory efficiency of the renal vasculature. During the control period, MAP averaged 91 +/- 0.5 and 89 +/- 0.4 mmHg, and RBF averaged 8.0 +/- 0.1 and 7.8 +/- 0.1 ml/min in the control and diabetic groups, respectively. Induction of diabetes with streptozotocin caused a marked and progressive increase in RBF in the diabetic rats, averaging 10 +/- 6% above control on day 1 of diabetes and 22 +/- 3 and 34 +/- 1% above control by the end of diabetes weeks 1 and 2. MAP increased approximately 9 mmHg during the 2 wk in the diabetic rats, and renal vascular resistance decreased. Transfer function analysis revealed significant increases in gain to positive values over the frequency ranges of both the TGF and myogenic mechanisms, beginning on day 1 of diabetes and continuing through day 14. These very rapid increases in RBF and transfer function gain suggest that autoregulation is impaired at the very onset of hyperglycemia in streptozotocin-induced type 1 diabetes and may play an important role in the increase in RBF and GFR in diabetes. Together with previous reports of decreases in chronically measured cardiac output and hindquarter blood flow, this suggests that there may be differential effects of diabetes on RBF versus nonrenal BF control.

  9. Differential screening of mutated SOD1 transgenic mice reveals early up-regulation of a fast axonal transport component in spinal cord motor neurons.

    PubMed

    Dupuis, L; de Tapia, M; René, F; Lutz-Bucher, B; Gordon, J W; Mercken, L; Pradier, L; Loeffler, J P

    2000-08-01

    In the present study we analyze the molecular mechanisms underlying motor neuron degeneration in familial amyotrophic lateral sclerosis (FALS). For this, we used a transgenic mouse model expressing the Cu/Zn superoxide dismutase (SOD1) gene with a Gly(86) to Arg (G86R) mutation equivalent to that found in a subset of human FALS. Using an optimized suppression subtractive hybridization method, a cDNA specifically up-regulated during the asymptomatic phase in the lumbar spinal cord of G86R mice was identified by sequence analysis as the KIF3-associated protein (KAP3), a regulator of fast axonal transport. RT-PCR analysis revealed that KAP3 induction was an early event arising long before axonal degeneration. Immunohistochemical studies further revealed that KAP3 protein predominantly accumulates in large motor neurons of the ventral spinal cord. We further demonstrated that KAP3 up-regulation occurs independent of any change in the other components of the kinesin II complex. However, since the ubiquitous KIF1A motor is up-regulated, our results show an early and complex rearrangement of the fast axonal transport machinery in the course of FALS pathology. Copyright 2000 Academic Press.

  10. Causes of blindness in a special education school.

    PubMed

    Onakpoya, O H; Adegbehingbe, B O; Omotoye, O J; Adeoye, A O

    2011-01-01

    Blind children and young adults have to overcome a lifetime of emotional, social and economic difficulties. They employ non-vision dependent methods for education. To assess the causes of blindness in a special school in southwestern Nigeria to aid the development of efficient blindness prevention programmes. A cross-sectional survey of the Ekiti State Special Education School, Nigeria was conducted in May-June 2008 after approval from the Ministry of Education. All students in the blind section were examined for visual acuity, pen-torch eye examination and dilated fundoscopy in addition to taking biodata and history. Thirty blind students with mean age of 18±7.3 years and male: female ratio of 1.7:1 were examined. Blindness resulted commonly from cataract eight (26.7%), glaucoma six (20%) retinitis pigmentosa four (16.7%) and posttraumatic phthysis bulbi two (6.7%). Blindness was avoidable in 18 (61%) of cases. Glaucoma blindness was associated with redness, pain, lacrimation and photophobia in 15 (50%) and hyphaema in 16.7% of students; none of these students were on any medication at the time of study. The causes of blindness in rehabilitation school for the blind are largely avoidable and glaucoma-blind pupils face additional painful eye related morbidity during rehabilitation. While preventive measures and early intervention are needful against childhood cataract and glaucoma, regular ophthalmic consultations and medications are needed especially for glaucoma blind pupils.

  11. Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components

    PubMed Central

    Dougados, M.; Combe, B.; Cantagrel, A.; Goupille, P.; Olive, P.; Schattenkirchner, M.; Meusser, S; Paimela, L; Rau, R.; Zeidler, H.; Leirisalo-Repo, M.; Peldan, K.

    1999-01-01

    OBJECTIVES—To investigate the potential clinical benefit of a combination therapy.
METHODS—205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying anti-rheumatoid drugs previously, with an early (⩽1 year duration), active (Disease Activity Score (DAS) > 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68).
RESULTS—The mean changes in the DAS during the one year follow up of the study was −1.15, −0.87, −1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007).
CONCLUSION—This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable.

 Keywords: rheumatoid arthritis; combination therapy; sulphasalazine; methotrexate PMID:10364900

  12. Evolutionary forward genomics reveals novel insights into the genes and pathways dysregulated in recurrent early pregnancy loss.

    PubMed

    Kosova, Gülüm; Stephenson, Mary D; Lynch, Vincent J; Ober, Carole

    2015-03-01

    Are the genes that gained novel expression in the endometria of Eutherian (placental) mammals more likely to be dysregulated in patients with endometrial-associated recurrent early pregnancy loss (REPL)? There was a significant enrichment of genes dysregulated in REPL patients among the Eutherian-specific endometrial genes. Pregnancy loss is the most common complication of human pregnancy. REPL has multiple etiologies, including dysregulation of endometrial function, leading to 'suboptimal' implantation. Although the implantation process is tightly regulated in Eutherian (placental) mammals, the molecular factors contributing to dysregulated endometrial gene expression patterns in women with REPL are largely unknown. Endometrial biopsies were obtained from 32 REPL patients during the mid-luteal phase, and evaluated for glandular development arrest based on elevated nuclear cyclin E levels in gland cells, and for out-of-phase endometrial development based on histology. Gene expression levels were measured using Illumina Human HT-12v4 BeadChip arrays. Differentially expressed genes were identified between patients with (i) out-of-phase (n = 10) versus normal (n = 22) histological dating and (ii) abnormally elevated (n = 9) versus normal (n = 23) cyclin E levels in the nuclei of endometrial glands, using a likelihood ratio test. Enrichment of dysregulated genes in REPL endometria among Eutherian-specific genes was tested by permutation. Gene ontology and pathway enrichment analyses were carried out for the dysregulated genes. Fifty-eight and eighty-one genes were identified as differentially expressed at P < 0.001 in women with out-of-phase histological dating and abnormally elevated glandular cyclin E levels, respectively. Genes that were recruited into endometrial expression during the evolution of pregnancy in Eutherian mammals were significantly enriched for dysregulated genes (P = 0.002 for histology, P = 0.021 for cyclin E), as well as for genes involved in

  13. Data mining reveals a network of early-response genes as a consensus signature of drug-induced in vitro and in vivo toxicity.

    PubMed

    Zhang, J D; Berntenis, N; Roth, A; Ebeling, M

    2014-06-01

    Gene signatures of drug-induced toxicity are of broad interest, but they are often identified from small-scale, single-time point experiments, and are therefore of limited applicability. To address this issue, we performed multivariate analysis of gene expression, cell-based assays, and histopathological data in the TG-GATEs (Toxicogenomics Project-Genomics Assisted Toxicity Evaluation system) database. Data mining highlights four genes-EGR1, ATF3, GDF15 and FGF21-that are induced 2 h after drug administration in human and rat primary hepatocytes poised to eventually undergo cytotoxicity-induced cell death. Modelling and simulation reveals that these early stress-response genes form a functional network with evolutionarily conserved structure and intrinsic dynamics. This is underlined by the fact that early induction of this network in vivo predicts drug-induced liver and kidney pathology with high accuracy. Our findings demonstrate the value of early gene-expression signatures in predicting and understanding compound-induced toxicity. The identified network can empower first-line tests that reduce animal use and costs of safety evaluation.

  14. RNA-Seq reveals the dynamic and diverse features of digestive enzymes during early development of Pacific white shrimp Litopenaeus vannamei.

    PubMed

    Wei, Jiankai; Zhang, Xiaojun; Yu, Yang; Li, Fuhua; Xiang, Jianhai

    2014-09-01

    The Pacific white shrimp (Litopenaeus vannamei), with high commercial value, has a typical metamorphosis pattern by going through embryo, nauplius, zoea, mysis and postlarvae during early development. Its diets change continually in this period, and a high mortality of larvae also occurs in this period. Since there is a close relationship between diets and digestive enzymes, a comprehensive investigation about the types and expression patterns of all digestive enzyme genes during early development of L. vannamei is of considerable significance for shrimp diets and larvae culture. Using RNA-Seq data, the types and expression characteristics of the digestive enzyme genes were analyzed during five different development stages (embryo, nauplius, zoea, mysis and postlarvae) in L. vannamei. Among the obtained 66,815 unigenes, 296 were annotated as 16 different digestive enzymes including five types of carbohydrase, seven types of peptidase and four types of lipase. Such a diverse suite of enzymes illustrated the capacity of L. vannamei to exploit varied diets to fit their nutritional requirements. The analysis of their dynamic expression patterns during development also indicated the importance of transcriptional regulation to adapt to the diet transition. Our study revealed the diverse and dynamic features of digestive enzymes during early development of L. vannamei. These results would provide support to better understand the physiological changes during diet transition. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Retrieval and phenomenology of autobiographical memories in blind individuals.

    PubMed

    Tekcan, Ali Í; Yılmaz, Engin; Kızılöz, Burcu Kaya; Karadöller, Dilay Z; Mutafoğlu, Merve; Erciyes, Aslı Aktan

    2015-01-01

    Although visual imagery is argued to be an essential component of autobiographical memory, there have been surprisingly few studies on autobiographical memory processes in blind individuals, who have had no or limited visual input. The purpose of the present study was to investigate how blindness affects retrieval and phenomenology of autobiographical memories. We asked 48 congenital/early blind and 48 sighted participants to recall autobiographical memories in response to six cue words, and to fill out the Autobiographical Memory Questionnaire measuring a number of variables including imagery, belief and recollective experience associated with each memory. Blind participants retrieved fewer memories and reported higher auditory imagery at retrieval than sighted participants. Moreover, within the blind group, participants with total blindness reported higher auditory imagery than those with some light perception. Blind participants also assigned higher importance, belief and recollection ratings to their memories than sighted participants. Importantly, these group differences remained the same for recent as well as childhood memories.

  16. A multicentre non-blinded randomised controlled trial to assess the impact of regular early specialist symptom control treatment on quality of life in malignant mesothelioma (RESPECT-MESO): study protocol for a randomised controlled trial.

    PubMed

    Gunatilake, Samal; Brims, Fraser J H; Fogg, Carole; Lawrie, Iain; Maskell, Nick; Forbes, Karen; Rahman, Najib; Morris, Steve; Ogollah, Reuben; Gerry, Stephen; Peake, Mick; Darlison, Liz; Chauhan, Anoop J

    2014-09-19

    Malignant pleural mesothelioma is an incurable cancer caused by exposure to asbestos. The United Kingdom has the highest death rate from mesothelioma in the world and this figure is increasing. Median survival is 8 to 12 months, and most patients have symptoms at diagnosis. The fittest patients may be offered chemotherapy with palliative intent. For patients not fit for systemic anticancer treatment, best supportive care remains the mainstay of management. A study from the United States examining advanced lung cancer showed that early specialist palliative care input improved patient health related quality of life and depression symptoms 12 weeks after diagnosis. While mesothelioma and advanced lung cancer share many symptoms and have a poor prognosis, oncology and palliative care services in the United Kingdom, and many other countries, vary considerably compared to the United States. The aim of this trial is to assess whether regular early symptom control treatment provided by palliative care specialists can improve health related quality of life in patients newly diagnosed with mesothelioma. This multicentre study is an non-blinded, randomised controlled, parallel group trial. A total of 174 patients with a new diagnosis of malignant pleural mesothelioma will be minimised with a random element in a 1:1 ratio to receive either 4 weekly regular early specialist symptom control care, or standard care. The primary outcome is health related quality of life for patients at 12 weeks. Secondary outcomes include health related quality of life for patients at 24 weeks, carer health related quality of life at 12 and 24 weeks, patient and carer mood at 12 and 24 weeks, overall survival and analysis of healthcare utilisation and cost. Current practice in the United Kingdom is to involve specialist palliative care towards the final weeks or months of a life-limiting illness. This study aims to investigate whether early, regular specialist care input can result in significant

  17. Plant based insect repellent and insecticide treated bed nets to protect against malaria in areas of early evening biting vectors: double blind randomised placebo controlled clinical trial in the Bolivian Amazon.

    PubMed

    Hill, N; Lenglet, A; Arnéz, A M; Carneiro, I

    2007-11-17

    To determine the effectiveness in reducing malaria of combining an insect repellent with insecticide treated bed nets compared with the nets alone in an area where vector mosquitoes feed in the early evening. A double blind, placebo controlled cluster-randomised clinical study. Rural villages and peri-urban districts in the Bolivian Amazon. 4008 individuals in 860 households. All individuals slept under treated nets; one group also used a plant based insect repellent each evening, a second group used placebo. Episodes of Plasmodium falciparum or P vivax malaria confirmed by rapid diagnostic test or blood slide, respectively. We analysed 15,174 person months at risk and found a highly significant 80% reduction in episodes of P vivax in the group that used treated nets and repellent (incidence rate ratio 0.20, 95% confidence interval 0.11 to 0.38, P<0.001). Numbers of P falciparum cases during the study were small and, after adjustment for age, an 82% protective effect was observed, although this was not significant (0.18, 0.02 to 1.40, P=0.10). Reported episodes of fever with any cause were reduced by 58% in the group that used repellent (0.42, 0.31 to 0.56, P<0.001). Insect repellents can provide protection against malaria. In areas where vectors feed in the early evening, effectiveness of treated nets can be significantly increased by using repellent between dusk and bedtime. This has important implications in malaria vector control programmes outside Africa and shows that the combined use of treated nets and insect repellents, as advocated for most tourists travelling to high risk areas, is fully justified. NCT 00144716.

  18. Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (II) Physiological and Symptomatic Responses of Early-Postmenopausal Women to Standardized doses of Maca in Double Blind, Randomized, Placebo-Controlled, Multi-Centre Clinical Study.

    PubMed

    Meissner, H O; Mscisz, A; Reich-Bilinska, H; Kapczynski, W; Mrozikiewicz, P; Bobkiewicz-Kozlowska, T; Kedzia, B; Lowicka, A; Barchia, I

    2006-12-01

    This was a double-blind, randomized, placebo-corrected, outpatient, multi-centre (five sites) clinical study, in which a total of 168 Caucasian early-postmenopausal women volunteers (age>49 years) participated after fulfilling the criteria: follicle stimulating hormone (FSH) >30 IU/ml and estrogen (E2) <40 pg/ml levels at admission. They were randomly allocated to Placebo and Pre-Gelatinized Organic Maca (Maca-GO) treatment, according to different monthly treatment sequences scheduled for each site. Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day) during three (Trial I; n=102) or four (Trial II; n=66) months study periods. At the baseline and follow- up monthly intervals, blood levels of FSH, E2, progesterone (PRG) and lutinizing hormone (LH), as well as serum cholesterol (CHOL), triglycerides (TRG), high- and low density lipoproteins (HDL and LDL) were measured. Menopausal symptoms were assessed according to Greene's Score (GMS) and Kupperman's Index (KMI). Data were analyzed using multivariate technique on blocs of monthly results in one model and Maca versus Placebo contrast in another model. A total of 124 women concluded the study. Maca-GO significantly stimulated production of E2 (P<0.001) with a simultaneous suppression (P<0.05) of blood FSH, increase (P<0.05) in HDL. Maca-GO significantly reduced both frequency and severity of individual menopausal symptoms (hot flushes and night sweating in particular) resulting in significant (P<0.001) alleviation of KMI (from 22 to 10), thus, offering an attractive non-hormonal addition to the choices available to early-postmenopausal women in the form of a natural plant alternative to Hormone Replacement Therapy (HRT) - hence, reducing dependence on hormone therapy programs.

  19. Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (II) Physiological and Symptomatic Responses of Early-Postmenopausal Women to Standardized doses of Maca in Double Blind, Randomized, Placebo-Controlled, Multi-Centre Clinical Study

    PubMed Central

    Meissner, H. O.; Mscisz, A.; Reich-Bilinska, H.; Kapczynski, W.; Mrozikiewicz, P.; Bobkiewicz-Kozlowska, T.; Kedzia, B.; Lowicka, A.; Barchia, I.

    2006-01-01

    This was a double-blind, randomized, placebo-corrected, outpatient, multi-centre (five sites) clinical study, in which a total of 168 Caucasian early-postmenopausal women volunteers (age>49 years) participated after fulfilling the criteria: follicle stimulating hormone (FSH) >30 IU/ml and estrogen (E2) <40 pg/ml levels at admission. They were randomly allocated to Placebo and Pre-Gelatinized Organic Maca (Maca-GO) treatment, according to different monthly treatment sequences scheduled for each site. Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day) during three (Trial I; n=102) or four (Trial II; n=66) months study periods. At the baseline and follow- up monthly intervals, blood levels of FSH, E2, progesterone (PRG) and lutinizing hormone (LH), as well as serum cholesterol (CHOL), triglycerides (TRG), high- and low density lipoproteins (HDL and LDL) were measured. Menopausal symptoms were assessed according to Greene’s Score (GMS) and Kupperman’s Index (KMI). Data were analyzed using multivariate technique on blocs of monthly results in one model and Maca versus Placebo contrast in another model. A total of 124 women concluded the study. Maca-GO significantly stimulated production of E2 (P<0.001) with a simultaneous suppression (P<0.05) of blood FSH, increase (P<0.05) in HDL. Maca-GO significantly reduced both frequency and severity of individual menopausal symptoms (hot flushes and night sweating in particular) resulting in significant (P<0.001) alleviation of KMI (from 22 to 10), thus, offering an attractive non-hormonal addition to the choices available to early-postmenopausal women in the form of a natural plant alternative to Hormone Replacement Therapy (HRT) – hence, reducing dependence on hormone therapy programs. PMID:23675005

  20. Reassessment of an Arabidopsis cell wall invertase inhibitor AtCIF1 reveals its role in seed germination and early seedling growth.

    PubMed

    Su, Tao; Wolf, Sebastian; Han, Mei; Zhao, Hongbo; Wei, Hongbin; Greiner, Steffen; Rausch, Thomas

    2016-01-01

    In higher plants, cell wall invertase (CWI) and vacuolar invertase (VI) are recognized as essential players in sugar metabolism and sugar signaling, thereby affecting source-sink interactions, plant development and responses to environmental cues. CWI and VI expression levels are transcriptionally controlled; however, both enzymes are also subject to posttranslational control by invertase inhibitor proteins. The physiological significances of inhibitor proteins during seed germination and early seedling development are not yet fully understood. Here, we demonstrate that the inhibitor isoform AtCIF1 impacted on seed germination and early seedling growth in Arabidopsis. The primary target of AtCIF1 was shown to be localized to the apoplast after expressing an AtCIF1 YFP-fusion construct in tobacco epidermis and transgenic Arabidopsis root. The analysis of expression patterns showed that AtCWI1 was co-expressed spatiotemporally with AtCIF1 within the early germinating seeds. Seed germination was observed to be accelerated independently of exogenous abscisic acid (ABA) in the AtCIF1 loss-of-function mutant cif1-1. This effect coincided with a drastic increase of CWI activity in cif1-1 mutant seeds by 24 h after the onset of germination, both in vitro and in planta. Accordingly, quantification of sugar content showed that hexose levels were significantly boosted in germinating seeds of the cif1-1 mutant. Further investigation of AtCIF1 overexpressors in Arabidopsis revealed a markedly suppressed CWI activity as well as delayed seed germination. Thus, we conclude that the posttranslational modulation of CWI activity by AtCIF1 helps to orchestrate seed germination and early seedling growth via fine-tuning sucrose hydrolysis and, possibly, sugar signaling.

  1. Unconditionally Secure Blind Signatures

    NASA Astrophysics Data System (ADS)

    Hara, Yuki; Seito, Takenobu; Shikata, Junji; Matsumoto, Tsutomu

    The blind signature scheme introduced by Chaum allows a user to obtain a valid signature for a message from a signer such that the message is kept secret for the signer. Blind signature schemes have mainly been studied from a viewpoint of computational security so far. In this paper, we study blind signatures in unconditional setting. Specifically, we newly introduce a model of unconditionally secure blind signature schemes (USBS, for short). Also, we propose security notions and their formalization in our model. Finally, we propose a construction method for USBS that is provably secure in our security notions.

  2. The Cortically Blind Infant: Educational Guidelines and Suggestions.

    ERIC Educational Resources Information Center

    Silverrain, Ann

    Cortical blindness is defined and its diagnosis is explained. Guidelines and sample activities are presented for use in a cognitive/visual/multi-sensory stimulation program to produce progress in cortically blind infants. The importance of using the eyes from birth through early development in order to form the nerve pathways responsible for…

  3. A Program for the Blind at Randolph Technical College.

    ERIC Educational Resources Information Center

    Wells, Richard T.

    Randolph Technical College (RTC) and the Division of Services for the Blind of the North Carolina Department of Human Resources have cooperated for two years on a program to provide blind students with the opportunity to receive instruction in a traditional classroom setting on a college campus. Problems encountered in the early stages of the…

  4. Change blindness, aging, and cognition

    PubMed Central

    Rizzo, Matthew; Sparks, JonDavid; McEvoy, Sean; Viamonte, Sarah; Kellison, Ida; Vecera, Shaun P.

    2011-01-01

    Change blindness (CB), the inability to detect changes in visual scenes, may increase with age and early Alzheimer’s disease (AD). To test this hypothesis, participants were asked to localize changes in natural scenes. Dependent measures were response time (RT), hit rate, false positives (FP), and true sensitivity (d′). Increased age correlated with increased sensitivity and RT; AD predicted even slower RT. Accuracy and RT were negatively correlated. Differences in FP were nonsignificant. CB correlated with impaired attention, working memory, and executive function. Advanced age and AD were associated with increased CB, perhaps due to declining memory and attention. CB could affect real-world tasks, like automobile driving. PMID:19051127

  5. Change blindness, aging, and cognition.

    PubMed

    Rizzo, Matthew; Sparks, Jondavid; McEvoy, Sean; Viamonte, Sarah; Kellison, Ida; Vecera, Shaun P

    2009-02-01

    Change blindness (CB), the inability to detect changes in visual scenes, may increase with age and early Alzheimer's disease (AD). To test this hypothesis, participants were asked to localize changes in natural scenes. Dependent measures were response time (RT), hit rate, false positives (FP), and true sensitivity (d'). Increased age correlated with increased sensitivity and RT; AD predicted even slower RT. Accuracy and RT were negatively correlated. Differences in FP were nonsignificant. CB correlated with impaired attention, working memory, and executive function. Advanced age and AD were associated with increased CB, perhaps due to declining memory and attention. CB could affect real-world tasks, like automobile driving.

  6. Early evolution of large micro-organisms with cytological complexity revealed by microanalyses of 3.4 Ga organic-walled microfossils.

    PubMed

    Sugitani, K; Mimura, K; Takeuchi, M; Lepot, K; Ito, S; Javaux, E J

    2015-11-01

    The Strelley Pool Formation (SPF) is widely distributed in the East Pilbara Terrane (EPT) of the Pilbara Craton, Western Australia, and represents a Paleoarchean shallow-water to subaerial environment. It was deposited ~3.4 billion years ago and displays well-documented carbonate stromatolites. Diverse putative microfossils (SPF microfossils) were recently reported from several localities in the East Strelley, Panorama, Warralong, and Goldsworthy greenstone belts. Thus, the SPF provides unparalleled opportunities to gain insights into a shallow-water to subaerial ecosystem on the early Earth. Our new micro- to nanoscale ultrastructural and microchemical studies of the SPF microfossils show that large (20-70 μm) lenticular organic-walled flanged microfossils retain their structural integrity, morphology, and chain-like arrangements after acid (HF-HCl) extraction (palynology). Scanning and transmitted electron microscopy of extracted microfossils revealed that the central lenticular body is either alveolar or hollow, and the wall is continuous with the surrounding smooth to reticulated discoidal flange. These features demonstrate the evolution of large micro-organisms able to form an acid-resistant recalcitrant envelope or cell wall with complex morphology and to form colonial chains in the Paleoarchean era. This study provides evidence of the evolution of very early and remarkable biological innovations, well before the presumed late emergence of complex cells. © 2015 John Wiley & Sons Ltd.

  7. Successful In Vitro Expansion and Differentiation of Cord Blood Derived CD34+ Cells into Early Endothelial Progenitor Cells Reveals Highly Differential Gene Expression

    PubMed Central

    Topcic, Denijal; Haviv, Izhak; Merivirta, Ruusu-Maaria; Agrotis, Alexander; Leitner, Ephraem; Jowett, Jeremy B.; Bode, Christoph; Lappas, Martha; Peter, Karlheinz

    2011-01-01

    Endothelial progenitor cells (EPCs) can be purified from peripheral blood, bone marrow or cord blood and are typically defined by a limited number of cell surface markers and a few functional tests. A detailed in vitro characterization is often restricted by the low cell numbers of circulating EPCs. Therefore in vitro culturing and expansion methods are applied, which allow at least distinguishing two different types of EPCs, early and late EPCs. Herein, we describe an in vitro culture technique with the aim to generate high numbers of phenotypically, functionally and genetically defined early EPCs from human cord blood. Characterization of EPCs was done by flow cytometry, immunofluorescence microscopy, colony forming unit (CFU) assay and endothelial tube formation assay. There was an average 48-fold increase in EPC numbers. EPCs expressed VEGFR-2, CD144, CD18, and CD61, and were positive for acetylated LDL uptake and ulex lectin binding. The cells stimulated endothelial tube formation only in co-cultures with mature endothelial cells and formed CFUs. Microarray analysis revealed highly up-regulated genes, including LL-37 (CAMP), PDK4, and alpha-2-macroglobulin. In addition, genes known to be associated with cardioprotective (GDF15) or pro-angiogenic (galectin-3) properties were also significantly up-regulated after a 72 h differentiation period on fibronectin. We present a novel method that allows to generate high numbers of phenotypically, functionally and genetically characterized early EPCs. Furthermore, we identified several genes newly linked to EPC differentiation, among them LL-37 (CAMP) was the most up-regulated gene. PMID:21858032

  8. New insights into roles of cell wall invertase in early seed development revealed by comprehensive spatial and temporal expression patterns of GhCWIN1 in cotton.

    PubMed

    Wang, Lu; Ruan, Yong-Ling

    2012-10-01

    Despite substantial evidence on the essential roles of cell wall invertase (CWIN) in seed filling, it remains largely unknown how CWIN exerts its regulation early in seed development, a critical stage that sets yield potential. To fill this knowledge gap, we systematically examined the spatial and temporal expression patterns of a major CWIN gene, GhCWIN1, in cotton (Gossypium hirsutum) seeds from prefertilization to prestorage phase. GhCWIN1 messenger RNA was abundant at the innermost seed coat cell layer at 5 d after anthesis but became undetectable at 10 d after anthesis, at the onset of its differentiation into transfer cells characterized by wall ingrowths, suggesting that CWIN may negatively regulate transfer cell differentiation. Within the filial tissues, GhCWIN1 transcript was detected in endosperm cells undergoing nuclear division but not in those cells at the cellularization stage, with similar results observed in Arabidopsis (Arabidopsis thaliana) endosperm for CWIN, AtCWIN4. These findings indicate a function of CWIN in nuclear division but not cell wall biosynthesis in endosperm, contrasting to the role proposed for sucrose synthase (Sus). Further analyses revealed a preferential expression pattern of GhCWIN1 and AtCWIN4 in the provascular region of the torpedo embryos in cotton and Arabidopsis seed, respectively, indicating a role of CWIN in vascular initiation. Together, these novel findings provide insights into the roles of CWIN in regulating early seed development spatially and temporally. By comparing with previous studies on Sus expression and in conjunction with the expression of other related genes, we propose models of CWIN- and Sus-mediated regulation of early seed development.

  9. Switch of Sensitivity Dynamics Revealed with DyGloSA Toolbox for Dynamical Global Sensitivity Analysis as an Early Warning for System's Critical Transition

    PubMed Central

    Baumuratova, Tatiana; Dobre, Simona; Bastogne, Thierry; Sauter, Thomas

    2013-01-01

    Systems with bifurcations may experience abrupt irreversible and often unwanted shifts in their performance, called critical transitions. For many systems like climate, economy, ecosystems it is highly desirable to identify indicators serving as early warnings of such regime shifts. Several statistical measures were recently proposed as early warnings of critical transitions including increased variance, autocorrelation and skewness of experimental or model-generated data. The lack of automatized tool for model-based prediction of critical transitions led to designing DyGloSA – a MATLAB toolbox for dynamical global parameter sensitivity analysis (GPSA) of ordinary differential equations models. We suggest that the switch in dynamics of parameter sensitivities revealed by our toolbox is an early warning that a system is approaching a critical transition. We illustrate the efficiency of our toolbox by analyzing several models with bifurcations and predicting the time periods when systems can still avoid going to a critical transition by manipulating certain parameter values, which is not detectable with the existing SA techniques. DyGloSA is based on the SBToolbox2 and contains functions, which compute dynamically the global sensitivity indices of the system by applying four main GPSA methods: eFAST, Sobol's ANOVA, PRCC and WALS. It includes parallelized versions of the functions enabling significant reduction of the computational time (up to 12 times). DyGloSA is freely available as a set of MATLAB scripts at http://bio.uni.lu/systems_biology/software/dyglosa. It requires installation of MATLAB (versions R2008b or later) and the Systems Biology Toolbox2 available at www.sbtoolbox2.org. DyGloSA can be run on Windows and Linux systems, -32 and -64 bits. PMID:24367574

  10. Switch of sensitivity dynamics revealed with DyGloSA toolbox for dynamical global sensitivity analysis as an early warning for system's critical transition.

    PubMed

    Baumuratova, Tatiana; Dobre, Simona; Bastogne, Thierry; Sauter, Thomas

    2013-01-01

    Systems with bifurcations may experience abrupt irreversible and often unwanted shifts in their performance, called critical transitions. For many systems like climate, economy, ecosystems it is highly desirable to identify indicators serving as early warnings of such regime shifts. Several statistical measures were recently proposed as early warnings of critical transitions including increased variance, autocorrelation and skewness of experimental or model-generated data. The lack of automatized tool for model-based prediction of critical transitions led to designing DyGloSA - a MATLAB toolbox for dynamical global parameter sensitivity analysis (GPSA) of ordinary differential equations models. We suggest that the switch in dynamics of parameter sensitivities revealed by our toolbox is an early warning that a system is approaching a critical transition. We illustrate the efficiency of our toolbox by analyzing several models with bifurcations and predicting the time periods when systems can still avoid going to a critical transition by manipulating certain parameter values, which is not detectable with the existing SA techniques. DyGloSA is based on the SBToolbox2 and contains functions, which compute dynamically the global sensitivity indices of the system by applying four main GPSA methods: eFAST, Sobol's ANOVA, PRCC and WALS. It includes parallelized versions of the functions enabling significant reduction of the computational time (up to 12 times). DyGloSA is freely available as a set of MATLAB scripts at http://bio.uni.lu/systems_biology/software/dyglosa. It requires installation of MATLAB (versions R2008b or later) and the Systems Biology Toolbox2 available at www.sbtoolbox2.org. DyGloSA can be run on Windows and Linux systems, -32 and -64 bits.

  11. A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils.

    PubMed

    Devchand, Pallavi R; Schmidt, Birgitta A; Primo, Valeria C; Zhang, Qing-yin; Arnaout, M Amin; Serhan, Charles N; Nikolic, Boris

    2005-02-01

    Lipoxin A(4) (LXA(4)) and aspirin-triggered 15-epi-LXA(4) are potent endogenous lipid mediators thought to define the inflammatory set-point. We used single prophylactic administrations of a synthetic aspirin-triggered lipoxin A(4) signal mimetic, ATLa, to probe dynamics of early host-donor interactions in a mouse model for the inflammation-associated multifactorial disease of allogeneic bone marrow transplant (BMT) -induced graft-vs.-host disease (GvHD). We first demonstrated that both host and donor are responsive to the ATLa signals. The simple and restricted regimen of a single prophylactic administration of ATLa [100 ng/mL to donor cells or 1 microg (approximately 50 microg/kg) i.v. to host] was sufficient to delay death. Clinical indicators of weight, skin lesions, diarrhea and eye inflammation were monitored. Histological analyses on day 45 post-BMT showed that the degree of cellular trafficking, particularly neutrophil infiltrate, and protection of end-organ target pathology are different, depending on whether the host or donor was treated with ATLa. Taken together, these results chart some ATLa protective effects on GvHD cellular dynamics over time and identify a previously unrecognized effect of host neutrophils in the early phase post-BMT as important determinants in the dynamics of GvHD onset and progression.-Devchand, P. R., Schmidt, B. A., Primo, V. C., Zhang, Q.-y., Arnaout, M. A., Serhan, C. N., Nikolic, B. A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils.

  12. Blindness after cardiac arrest

    PubMed Central

    Sabah, A. H.

    1968-01-01

    Three cases of isolated blindness after cardiac arrest are described. Blindness was associated with normal pupillary light reflexes and no observable changes in the fundi, features identifying it as cortical. Possible mechanisms have been discussed. It is suggested that this complication is more common than has been reported in the literature. PMID:5667108

  13. "Color-Blind" Racism.

    ERIC Educational Resources Information Center

    Carr, Leslie G.

    Examining race relations in the United States from a historical perspective, this book explains how the constitution is racist and how color blindness is actually a racist ideology. It is argued that Justice Harlan, in his dissenting opinion in Plessy v. Ferguson, meant that the constitution and the law must remain blind to the existence of race…

  14. Perceptual Repetition Blindness Effects

    NASA Technical Reports Server (NTRS)

    Hochhaus, Larry; Johnston, James C.; Null, Cynthia H. (Technical Monitor)

    1994-01-01

    The phenomenon of repetition blindness (RB) may reveal a new limitation on human perceptual processing. Recently, however, researchers have attributed RB to post-perceptual processes such as memory retrieval and/or reporting biases. The standard rapid serial visual presentation (RSVP) paradigm used in most RB studies is, indeed, open to such objections. Here we investigate RB using a "single-frame" paradigm introduced by Johnston and Hale (1984) in which memory demands are minimal. Subjects made only a single judgement about whether one masked target word was the same or different than a post-target probe. Confidence ratings permitted use of signal detection methods to assess sensitivity and bias effects. In the critical condition for RB a precue of the post-target word was provided prior to the target stimulus (identity precue), so that the required judgement amounted to whether the target did or did not repeat the precue word. In control treatments, the precue was either an unrelated word or a dummy.

  15. How "Blind" Are Double-Blind Studies?

    ERIC Educational Resources Information Center

    Margraf, Jurgen; And Others

    1991-01-01

    Compared alprazolam, imipramine, and placebo in the treatment of panic disorder patients (n=59) to investigate concerns about the internal validity of the double-blind design. Found that the great majority of patients and physicians were able to rate accurately whether active drug or placebo had been given and physicians could distinguish between…

  16. Blinded by Irrelevance: Pure Irrelevance Induced "Blindness"

    ERIC Educational Resources Information Center

    Eitam, Baruch; Yeshurun, Yaffa; Hassan, Kinneret

    2013-01-01

    To what degree does our representation of the immediate world depend solely on its relevance to what we are currently doing? We examined whether relevance per se can cause "blindness," even when there is no resource limitation. In a novel paradigm, people looked at a colored circle surrounded by a differently colored ring--the task relevance of…

  17. Genomic Reconstruction of the History of Native Sheep Reveals the Peopling Patterns of Nomads and the Expansion of Early Pastoralism in East Asia

    PubMed Central

    Zhao, Yong-Xin; Yang, Ji; Lv, Feng-Hua; Hu, Xiao-Ju; Xie, Xing-Long; Zhang, Min; Li, Wen-Rong; Liu, Ming-Jun; Wang, Yu-Tao; Li, Jin-Quan; Liu, Yong-Gang; Ren, Yan-Ling; Wang, Feng; Hehua, EEr; Kantanen, Juha; Arjen Lenstra, Johannes; Han, Jian-Lin; Li, Meng-Hua

    2017-01-01

    Abstract China has a rich resource of native sheep (Ovis aries) breeds associated with historical movements of several nomadic societies. However, the history of sheep and the associated nomadic societies in ancient China remains poorly understood. Here, we studied the genomic diversity of Chinese sheep using genome-wide SNPs, mitochondrial and Y-chromosomal variations in > 1,000 modern samples. Population genomic analyses combined with archeological records and historical ethnic demographics data revealed genetic signatures of the origins, secondary expansions and admixtures, of Chinese sheep thereby revealing the peopling patterns of nomads and the expansion of early pastoralism in East Asia. Originating from the Mongolian Plateau ∼5,000‒5,700 years ago, Chinese sheep were inferred to spread in the upper and middle reaches of the Yellow River ∼3,000‒5,000 years ago following the expansions of the Di-Qiang people. Afterwards, sheep were then inferred to reach the Qinghai-Tibetan and Yunnan-Kweichow plateaus ∼2,000‒2,600 years ago by following the north-to-southwest routes of the Di-Qiang migration. We also unveiled two subsequent waves of migrations of fat-tailed sheep into northern China, which were largely commensurate with the migrations of ancestors of Hui Muslims eastward and Mongols southward during the 12th‒13th centuries. Furthermore, we revealed signs of argali introgression into domestic sheep, extensive historical mixtures among domestic populations and strong artificial selection for tail type and other traits, reflecting various breeding strategies by nomadic societies in ancient China. PMID:28645168

  18. Genomic Reconstruction of the History of Native Sheep Reveals the Peopling Patterns of Nomads and the Expansion of Early Pastoralism in East Asia.

    PubMed

    Zhao, Yong-Xin; Yang, Ji; Lv, Feng-Hua; Hu, Xiao-Ju; Xie, Xing-Long; Zhang, Min; Li, Wen-Rong; Liu, Ming-Jun; Wang, Yu-Tao; Li, Jin-Quan; Liu, Yong-Gang; Ren, Yan-Ling; Wang, Feng; Hehua, EEr; Kantanen, Juha; Arjen Lenstra, Johannes; Han, Jian-Lin; Li, Meng-Hua

    2017-09-01

    China has a rich resource of native sheep (Ovis aries) breeds associated with historical movements of several nomadic societies. However, the history of sheep and the associated nomadic societies in ancient China remains poorly understood. Here, we studied the genomic diversity of Chinese sheep using genome-wide SNPs, mitochondrial and Y-chromosomal variations in > 1,000 modern samples. Population genomic analyses combined with archeological records and historical ethnic demographics data revealed genetic signatures of the origins, secondary expansions and admixtures, of Chinese sheep thereby revealing the peopling patterns of nomads and the expansion of early pastoralism in East Asia. Originating from the Mongolian Plateau ∼5,000‒5,700 years ago, Chinese sheep were inferred to spread in the upper and middle reaches of the Yellow River ∼3,000‒5,000 years ago following the expansions of the Di-Qiang people. Afterwards, sheep were then inferred to reach the Qinghai-Tibetan and Yunnan-Kweichow plateaus ∼2,000‒2,600 years ago by following the north-to-southwest routes of the Di-Qiang migration. We also unveiled two subsequent waves of migrations of fat-tailed sheep into northern China, which were largely commensurate with the migrations of ancestors of Hui Muslims eastward and Mongols southward during the 12th‒13th centuries. Furthermore, we revealed signs of argali introgression into domestic sheep, extensive historical mixtures among domestic populations and strong artificial selection for tail type and other traits, reflecting various breeding strategies by nomadic societies in ancient China. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  19. The origin of snakes: revealing the ecology, behavior, and evolutionary history of early snakes using genomics, phenomics, and the fossil record.

    PubMed

    Hsiang, Allison Y; Field, Daniel J; Webster, Timothy H; Behlke, Adam D B; Davis, Matthew B; Racicot, Rachel A; Gauthier, Jacques A

    2015-05-20

    The highly derived morphology and astounding diversity of snakes has long inspired debate regarding the ecological and evolutionary origin of both the snake total-group (Pan-Serpentes) and crown snakes (Serpentes). Although speculation abounds on the ecology, behavior, and provenance of the earliest snakes, a rigorous, clade-wide analysis of snake origins has yet to be attempted, in part due to a dearth of adequate paleontological data on early stem snakes. Here, we present the first comprehensive analytical reconstruction of the ancestor of crown snakes and the ancestor of the snake total-group, as inferred using multiple methods of ancestral state reconstruction. We use a combined-data approach that includes new information from the fossil record on extinct crown snakes, new data on the anatomy of the stem snakes Najash rionegrina, Dinilysia patagonica, and Coniophis precedens, and a deeper understanding of the distribution of phenotypic apomorphies among the major clades of fossil and Recent snakes. Additionally, we infer time-calibrated phylogenies using both new 'tip-dating' and traditional node-based approaches, providing new insights on temporal patterns in the early evolutionary history of snakes. Comprehensive ancestral state reconstructions reveal that both the ancestor of crown snakes and the ancestor of total-group snakes were nocturnal, widely foraging, non-constricting stealth hunters. They likely consumed soft-bodied vertebrate and invertebrate prey that was subequal to head size, and occupied terrestrial settings in warm, well-watered, and well-vegetated environments. The snake total-group - approximated by the Coniophis node - is inferred to have originated on land during the middle Early Cretaceous (~128.5 Ma), with the crown-group following about 20 million years later, during the Albian stage. Our inferred divergence dates provide strong evidence for a major radiation of henophidian snake diversity in the wake of the Cretaceous-Paleogene (K

  20. Design, conduct, and analyses of Breast International Group (BIG) 1-98: a randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer.

    PubMed

    Giobbie-Hurder, Anita; Price, Karen N; Gelber, Richard D

    2009-06-01

    Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. From 1998-2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. BIG 1-98 is an example of an enriched design, involving complementary analyses addressing different questions several years

  1. Methyltestosterone-induced night blindness.

    PubMed

    Nisbett, S B; Parker, J A; Habal, F

    1985-12-01

    A 59-year-old man presented with a 3-month history of night blindness and a 9-month history of steatorrhea. Both symptoms had appeared after he had begun taking methyltestosterone. Investigations revealed low serum levels of carotene (0.1 mmol/L) and vitamin A (0.4 to 0.7 mmol/L), anomalous colour perception, elevation of the rod threshold by 3.5 log units in dark adaptometry, and decreased b-wave amplitudes in photopic and scotopic electroretinograms. No biochemical evidence of cholestasis was elicited. The symptoms and the biochemical and electrophysiologic abnormalities resolved within 9 months of the discontinuation of methyltestosterone.

  2. Failure to Detect Deaf-Blindness in a Population of People with Intellectual Disability

    ERIC Educational Resources Information Center

    Fellinger, J.; Holzinger, D.; Dirmhirn, A.; van Dijk, J.; Goldberg, D.

    2009-01-01

    Background: Early identification of deaf-blindness is essential to ensure appropriate management. Previous studies indicate that deaf-blindness is often missed. We aim to discover the extent to which deaf-blindness in people with intellectual disability (ID) is undiagnosed. Method: A survey was made of the 253 residents of an institute offering…

  3. Transcriptome analyses of rhesus monkey preimplantation embryos reveal a reduced capacity for DNA double-strand break repair in primate oocytes and early embryos

    PubMed Central

    Wang, Xinyi; Liu, Denghui; He, Dajian; Suo, Shengbao; Xia, Xian; He, Xiechao; Han, Jing-Dong J.; Zheng, Ping

    2017-01-01

    Preimplantation embryogenesis encompasses several critical events including genome reprogramming, zygotic genome activation (ZGA), and cell-fate commitment. The molecular basis of these processes remains obscure in primates in which there is a high rate of embryo wastage. Thus, understanding the factors involved in genome reprogramming and ZGA might help reproductive success during this susceptible period of early development and generate induced pluripotent stem cells with greater efficiency. Moreover, explaining the molecular basis responsible for embryo wastage in primates will greatly expand our knowledge of species evolution. By using RNA-seq in single and pooled oocytes and embryos, we defined the transcriptome throughout preimplantation development in rhesus monkey. In comparison to archival human and mouse data, we found that the transcriptome dynamics of monkey oocytes and embryos were very similar to those of human but very different from those of mouse. We identified several classes of maternal and zygotic genes, whose expression peaks were highly correlated with the time frames of genome reprogramming, ZGA, and cell-fate commitment, respectively. Importantly, comparison of the ZGA-related network modules among the three species revealed less robust surveillance of genomic instability in primate oocytes and embryos than in rodents, particularly in the pathways of DNA damage signaling and homology-directed DNA double-strand break repair. This study highlights the utility of monkey models to better understand the molecular basis for genome reprogramming, ZGA, and genomic stability surveillance in human early embryogenesis and may provide insights for improved homologous recombination-mediated gene editing in monkey. PMID:28223401

  4. Early onset of magma ocean crystallization revealed by coupled 146,147Sm-142,143Nd systematics of Nulliak ultramafics (3.78 Ga, Labrador)

    NASA Astrophysics Data System (ADS)

    Morino, P.; Caro, G.; Reisberg, L. C.

    2015-12-01

    Early onset of magma ocean crystallization revealed by coupled 146,147Sm-142,143Nd systematics of Nulliak ultramafics (3.78 Ga, Labrador) Precillia Morino1, Guillaume Caro1, Laurie Reisberg 1 1CRPG-CNRS, Université de Lorraine, Nancy, France Coupled 146,147Sm-142,143Nd systematics provides constraints on the timing of magma ocean crystallization on Mars, the Moon and Vesta. Estimates for the Earth's mantle, however, are less accurate owing to the sparsity of Eoarchean mantle-derived rocks with undisturbed 147Sm-143Nd systematics. This study attempts to establish a coherent 142,143Nd dataset for the Eoarchean mantle using well-preserved ultramafic rocks from the Nulliak assemblage (Labrador). Samples include meta-dunites, -pyroxenites and -peridotites exhibiting only minor serpentinization and limited element mobility. The presence of "Barberton type" komatiitic compositions (low Al/Ti, HREE depletion) is suggestive of a deep mantle source. 146,147Sm-142,143Nd and 187Re-187Os analyses yield a crystallization age of 3.78±0.09 Ga with ɛ143Ndi=1.5±0.2 and ɛ142Nd=8.6±2 ppm. This 142,143Nd signature yields a model age of mantle differentiation of 4.43±0.05 Ga (assuming a BSE with chondritic Sm/Nd and ɛ142Nd=0). Superchondritic Sm/Nd compositions for the BSE would translate into older model ages. Irrespective of the choice of primitive mantle composition, Nulliak ultramafics provide differentiation ages 100 Ma older than those estimated from Akilia tonalites but remarkably similar to that estimated from the 2.7 Ga Theo's flow (Abitibi). If Nulliak ultramafics originated from deep melting of a hot plume, their model age could reflect the early onset of magma ocean crystallization in the lowermost mantle.

  5. Validity of False Belief Tasks in Blind Children

    ERIC Educational Resources Information Center

    Brambring, Michael; Asbrock, Doreen

    2010-01-01

    Previous studies have reported that congenitally blind children without any additional impairment reveal a developmental delay of at least 4 years in perspective taking based on testing first-order false-belief tasks. These authors interpret this delay as a sign of autism-like behavior. However, the delay may be caused by testing blind children…

  6. Genome-resolved metaproteomic characterization of preterm infant gut microbiota development reveals species-specific metabolic shifts and variabilities during early life

    DOE PAGES

    Xiong, Weili; Brown, Christopher T.; Morowitz, Michael J.; ...

    2017-07-10

    acids) utilization and short-chain fatty acid production. Overall, this study reports species-specific proteome profiles and metabolic functions of human gut microbiota during early colonization. In particular, our work contributes to reveal microbiota-associated shifts and variations in the metabolism of three major nutrient sources and short-chain fatty acid during colonization of preterm infant gut.« less

  7. Genome-resolved metaproteomic characterization of preterm infant gut microbiota development reveals species-specific metabolic shifts and variabilities during early life

    SciTech Connect

    Xiong, Weili; Brown, Christopher T.; Morowitz, Michael J.

    acids) utilization and short-chain fatty acid production. Overall, this study reports species-specific proteome profiles and metabolic functions of human gut microbiota during early colonization. In particular, our work contributes to reveal microbiota-associated shifts and variations in the metabolism of three major nutrient sources and short-chain fatty acid during colonization of preterm infant gut.« less

  8. Genome-resolved metaproteomic characterization of preterm infant gut microbiota development reveals species-specific metabolic shifts and variabilities during early life.

    PubMed

    Xiong, Weili; Brown, Christopher T; Morowitz, Michael J; Banfield, Jillian F; Hettich, Robert L

    2017-07-10

    ) utilization and short-chain fatty acid production. Overall, this study reports species-specific proteome profiles and metabolic functions of human gut microbiota during early colonization. In particular, our work contributes to reveal microbiota-associated shifts and variations in the metabolism of three major nutrient sources and short-chain fatty acid during colonization of preterm infant gut.

  9. Single cell qPCR reveals that additional HAND2 and microRNA-1 facilitate the early reprogramming progress of seven-factor-induced human myocytes

    PubMed Central

    Bektik, Emre; Dennis, Adrienne; Prasanna, Prateek; Madabhushi, Anant

    2017-01-01

    The direct reprogramming of cardiac fibroblasts into induced cardiomyocyte (CM)-like cells (iCMs) holds great promise in restoring heart function. We previously found that human fibroblasts could be reprogrammed toward CM-like cells by 7 reprogramming factors; however, iCM reprogramming in human fibroblasts is both more difficult and more time-intensive than that in mouse cells. In this study, we investigated if additional reprogramming factors could quantitatively and/or qualitatively improve 7-factor-mediated human iCM reprogramming by single-cell quantitative PCR. We first validated 46 pairs of TaqMan® primers/probes that had sufficient efficiency and sensitivity to detect the significant difference of gene expression between individual H9 human embryonic stem cell (ESC)-differentiated CMs (H9CMs) and human fibroblasts. The expression profile of these 46 genes revealed an improved reprogramming in 12-week iCMs compared to 4-week iCMs reprogrammed by 7 factors, indicating a prolonged stochastic phase during human iCM reprogramming. Although none of additional one reprogramming factor yielded a greater number of iCMs, our single-cell qPCR revealed that additional HAND2 or microRNA-1 could facilitate the silencing of fibroblast genes and yield a better degree of reprogramming in more reprogrammed iCMs. Noticeably, the more HAND2 expressed, the higher-level were cardiac genes activated in 7Fs+HAND2-reprogrammed iCMs. In conclusion, HAND2 and microRNA-1 could help 7 factors to facilitate the early progress of iCM-reprogramming from human fibroblasts. Our study provides valuable information to further optimize a method of direct iCM-reprogramming in human cells. PMID:28796841

  10. Single cell qPCR reveals that additional HAND2 and microRNA-1 facilitate the early reprogramming progress of seven-factor-induced human myocytes.

    PubMed

    Bektik, Emre; Dennis, Adrienne; Prasanna, Prateek; Madabhushi, Anant; Fu, Ji-Dong

    2017-01-01

    The direct reprogramming of cardiac fibroblasts into induced cardiomyocyte (CM)-like cells (iCMs) holds great promise in restoring heart function. We previously found that human fibroblasts could be reprogrammed toward CM-like cells by 7 reprogramming factors; however, iCM reprogramming in human fibroblasts is both more difficult and more time-intensive than that in mouse cells. In this study, we investigated if additional reprogramming factors could quantitatively and/or qualitatively improve 7-factor-mediated human iCM reprogramming by single-cell quantitative PCR. We first validated 46 pairs of TaqMan® primers/probes that had sufficient efficiency and sensitivity to detect the significant difference of gene expression between individual H9 human embryonic stem cell (ESC)-differentiated CMs (H9CMs) and human fibroblasts. The expression profile of these 46 genes revealed an improved reprogramming in 12-week iCMs compared to 4-week iCMs reprogrammed by 7 factors, indicating a prolonged stochastic phase during human iCM reprogramming. Although none of additional one reprogramming factor yielded a greater number of iCMs, our single-cell qPCR revealed that additional HAND2 or microRNA-1 could facilitate the silencing of fibroblast genes and yield a better degree of reprogramming in more reprogrammed iCMs. Noticeably, the more HAND2 expressed, the higher-level were cardiac genes activated in 7Fs+HAND2-reprogrammed iCMs. In conclusion, HAND2 and microRNA-1 could help 7 factors to facilitate the early progress of iCM-reprogramming from human fibroblasts. Our study provides valuable information to further optimize a method of direct iCM-reprogramming in human cells.

  11. Blinded by irrelevance: pure irrelevance induced "blindness".

    PubMed

    Eitam, Baruch; Yeshurun, Yaffa; Hassan, Kinneret

    2013-06-01

    To what degree does our representation of the immediate world depend solely on its relevance to what we are currently doing? We examined whether relevance per se can cause "blindness," even when there is no resource limitation. In a novel paradigm, people looked at a colored circle surrounded by a differently colored ring-the task relevance of which was previously manipulated-and were subsequently asked to identify these colors. Whereas knowledge of the task-relevant color was near perfect, up to a quarter of the participants could not name the color of the irrelevant stimulus, even though a control experiment indicated there were sufficient resources to process both stimuli. The results are a first demonstration of blindness when mental resources are clearly available and challenge attentional theories predicting strong selection only when resources are taxed. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  12. Behaviors of Sighted Individuals Perceived by Blind Persons as Hindrances to Self-Reliance in Blind Persons.

    ERIC Educational Resources Information Center

    Rickelman, Bonnie L.; Blaylock, Jerry N.

    1983-01-01

    Situations in which sighted people behaved inappropiately toward blind individuals were recalled by 60 blind subjects, who described their reactions and feelings and offered suggestions for sighted people. A lack of knowledge and understanding of the skills, abilities, and feelings of visually impaired individuals were revealed. (SEW)

  13. Blinding laser weapons.

    PubMed

    Peters, A

    1996-01-01

    At its October 1995 Review Conference, the Convention on Conventional Weapons added a protocol banning the use and transfer of blinding laser weapons. The background to, and significance and limitations of this ban are discussed.

  14. Facts About Color Blindness

    MedlinePlus

    ... color perception of its employees, such as graphic design, photography, and food quality inspection. The Farnsworth Lantern ... challenging. Color blindness can go undetected for some time since children will often try to hide their ...

  15. Issues in Traumatic Blindness.

    ERIC Educational Resources Information Center

    Dale, B.

    1992-01-01

    This article discusses factors related to individuals with sudden blindness, focusing on the visually impaired client's readiness for rehabilitation, the reactions of family members and friends, and personality variables. Two cases illustrate the adjustment process and eventual rehabilitation. (DB)

  16. Bioinformatics Analysis Reveals Distinct Molecular Characteristics of Hepatitis B-Related Hepatocellular Carcinomas from Very Early to Advanced Barcelona Clinic Liver Cancer Stages.

    PubMed

    Kong, Fan-Yun; Wei, Xiao; Zhou, Kai; Hu, Wei; Kou, Yan-Bo; You, Hong-Juan; Liu, Xiao-Mei; Zheng, Kui-Yang; Tang, Ren-Xian

    2016-01-01

    Hepatocellular carcinoma (HCC)is the fifth most common malignancy associated with high mortality. One of the risk factors for HCC is chronic hepatitis B virus (HBV) infection. The treatment strategy for the disease is dependent on the stage of HCC, and the Barcelona clinic liver cancer (BCLC) staging system is used in most HCC cases. However, the molecular characteristics of HBV-related HCC in different BCLC stages are still unknown. Using GSE14520 microarray data from HBV-related HCC cases with BCLC stages from 0 (very early stage) to C (advanced stage) in the gene expression omnibus (GEO) database, differentially expressed genes (DEGs), including common DEGs and unique DEGs in different BCLC stages, were identified. These DEGs were located on different chromosomes. The molecular functions and biology pathways of DEGs were identified by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the interactome networks of DEGs were constructed using the NetVenn online tool. The results revealed that both common DEGs and stage-specific DEGs were associated with various molecular functions and were involved in special biological pathways. In addition, several hub genes were found in the interactome networks of DEGs. The identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of HBV-related HCC through the different BCLC stages, and might be used as staging biomarkers or molecular targets for the treatment of HCC with HBV infection.

  17. Revealing Early Steps of α2β1 Integrin-mediated Adhesion to Collagen Type I by Using Single-Cell Force Spectroscopy

    PubMed Central

    Taubenberger, Anna; Cisneros, David A.; Friedrichs, Jens; Puech, Pierre-Henri; Muller, Daniel J.

    2007-01-01

    We have characterized early steps of α2β1 integrin-mediated cell adhesion to a collagen type I matrix by using single-cell force spectroscopy. In agreement with the role of α2β1 as a collagen type I receptor, α2β1-expressing Chinese hamster ovary (CHO)-A2 cells spread rapidly on the matrix, whereas α2β1-negative CHO wild-type cells adhered poorly. Probing CHO-A2 cell detachment forces over a contact time range of 600 s revealed a nonlinear adhesion response. During the first 60 s, cell adhesion increased slowly, and forces associated with the smallest rupture events were consistent with the breakage of individual integrin–collagen bonds. Above 60 s, a fraction of cells rapidly switched into an activated adhesion state marked by up to 10-fold increased detachment forces. Elevated overall cell adhesion coincided with a rise of the smallest rupture forces above the value required to break a single-integrin–collagen bond, suggesting a change from single to cooperative receptor binding. Transition into the activated adhesion mode and the increase of the smallest rupture forces were both blocked by inhibitors of actomyosin contractility. We therefore propose a two-step mechanism for the establishment of α2β1-mediated adhesion as weak initial, single-integrin–mediated binding events are superseded by strong adhesive interactions involving receptor cooperativity and actomyosin contractility. PMID:17314408

  18. Global analysis of human duplicated genes reveals the relative importance of whole-genome duplicates originated in the early vertebrate evolution.

    PubMed

    Acharya, Debarun; Ghosh, Tapash C

    2016-01-22

    Gene duplication is a genetic mutation that creates functionally redundant gene copies that are initially relieved from selective pressures and may adapt themselves to new functions with time. The levels of gene duplication may vary from small-scale duplication (SSD) to whole genome duplication (WGD). Studies with yeast revealed ample differences between these duplicates: Yeast WGD pairs were functionally more similar, less divergent in subcellular localization and contained a lesser proportion of essential genes. In this study, we explored the differences in evolutionary genomic properties of human SSD and WGD genes, with the identifiable human duplicates coming from the two rounds of whole genome duplication occurred early in vertebrate evolution. We observed that these two groups of duplicates were also dissimilar in terms of their evolutionary and genomic properties. But interestingly, this is not like the same observed in yeast. The human WGDs were found to be functionally less similar, diverge more in subcellular level and contain a higher proportion of essential genes than the SSDs, all of which are opposite from yeast. Additionally, we explored that human WGDs were more divergent in their gene expression profile, have higher multifunctionality and are more often associated with disease, and are evolutionarily more conserved than human SSDs. Our study suggests that human WGD duplicates are more divergent and entails the adaptation of WGDs to novel and important functions that consequently lead to their evolutionary conservation in the course of evolution.

  19. Proteomic analysis of stipe explants reveals differentially expressed proteins involved in early direct somatic embryogenesis of the tree fern Cyathea delgadii Sternb.

    PubMed

    Domżalska, Lucyna; Kędracka-Krok, Sylwia; Jankowska, Urszula; Grzyb, Małgorzata; Sobczak, Mirosław; Rybczyński, Jan J; Mikuła, Anna

    2017-05-01

    Using cyto-morphological analysis of somatic embryogenesis (SE) in the tree fern Cyathea delgadii as a guide, we performed a comparative proteomic analysis in stipe explants undergoing direct SE. Plant material was cultured on hormone-free medium supplemented with 2% sucrose. Phenol extracted proteins were separated using two-dimensional gel electrophoresis (2-DE) and mass spectrometry was performed for protein identification. A total number of 114 differentially regulated proteins was identified during early SE, i.e. when the first cell divisions started and several-cell pro-embryos were formed. Proteins were assigned to seven functional categories: carbohydrate metabolism, protein metabolism, cell organization, defense and stress responses, amino acid metabolism, purine metabolism, and fatty acid metabolism. Carbohydrate and protein metabolism were found to be the most sensitive SE functions with the greatest number of alterations in the intensity of spots in gel. Differences, especially in non-enzymatic and structural protein abundance, are indicative for cell organization, including cytoskeleton rearrangement and changes in cell wall components. The highest induced changes concern those enzymes related to fatty acid metabolism. Global analysis of the proteome reveals several proteins that can represent markers for the first 16days of SE induction and expression in fern. The findings of this research improve the understanding of molecular processes involved in direct SE in C. delgadii. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Early Triassic change in the erosional level in the eastern part of the Bohemian Massif revealed by detrital garnet assemblages from the Buntsandstein siliciclastics of southern Poland

    NASA Astrophysics Data System (ADS)

    Kowal-Linka, Monika; Walczak, Klaudia

    2017-04-01

    Garnets, as constituents of various magmatic and metamorphic rocks, show different chemical compositions depending on the type of magma or primary rock, the temperature, and the pressure. This diversity of chemical compositions makes detrital garnets a very useful tool for provenance analysis and deciphering changes in erosional levels of source areas. Preliminary works reveal that the Lower and Middle Buntsandstein terrigenous and marine sandstones cropping out in southern Poland (50˚ 28'20"N, 18˚ 04'33"E and 50˚ 27'35"N, 18˚ 07'23"E) are characterized by very different heavy mineral assemblages (HMA) and types of detrital garnets. The aim of the research is to recognize the source areas and causes of these distinct variations using petrographic analysis, heavy mineral analysis, and electron probe microanalysis. During the Early Triassic, the area under study was located between two landmasses: the eastern margin of the Bohemian Massif (BM) to the west and Pre-Carpathian Land (PCL) to the east. Presently, the sampled area is situated ˜50 km from the NE margin of the BM, which consists of many garnet-bearing rocks and is a presumable source area for the examined grains. The PCL was hidden under the Carpathians during the Alpine orogeny and knowledge of its composition is very limited. Petrographic analysis shows that the older sandstones are red to rusty quartz arenites with a hematite-rich matrix and well-rounded grains (aeolian deposits). The younger sandstones are bicolored quartz wackes (dirty pink with grey patches) with a calcite matrix and angular to rounded grains (shallow marine deposits). The arenites contain zircon, tourmaline, and rutile grains accompanied by garnet, staurolite, apatite, and topaz. The opaque heavy minerals include ilmenite, ilmenite-rutile aggregates, magnetite and rarely chromian spinel. In contrast, the HMA from the wackes consist mostly of garnets, while the minerals listed above occur in subordinate amounts. The garnets from

  1. [Survey and treatment of the blind in Xinhui, Guangdong, China].

    PubMed

    Mao, W; Xu, J; Wu, Z; Zhu, S; Zhang, X; Li, X; Li, X; Deng, D; Chen, B; Li, S

    1992-12-01

    Co-operating with Helen Keller International (HKI) in 1987 and 1988, Zhongshan Ophthalmic Center made a large scale prevalent survey of the blind in Xinhui, Guangdong, China. Three screening methods were used in the project. The first was a house-to-house visit by ophthalmologists. The second was performed initially by trained country health workers and then checked by ophthalmologists. In the third one, the blind people were asked to come together to be examined by ophthalmologists. The second method was found to be the most effective. The survey revealed that the prevalent rate of blindness was 0.24% in the county. Of all the blind, 89% were over 50 years old, 73% were females. Cataract accounted for 47% of the blindness. Thirty percent of the blind from cataract received surgical treatment. The postoperative re-examination half a year later showed that the corrected visual acuity in 86% of the patients was more than 0.05.

  2. Overview on Deaf-Blindness.

    ERIC Educational Resources Information Center

    Miles, Barbara

    1995-01-01

    This overview provides basic information on the causes of deaf-blindness and the particular challenges faced by individuals with deaf-blindness. Causes of deaf-blindness include various syndromes, multiple congenital anomalies, prematurity, congenital prenatal dysfunction, and various postnatal causes. Differences between people deaf-blind from…

  3. Oral dydrogesterone treatment during early pregnancy to prevent recurrent pregnancy loss and its role in modulation of cytokine production: a double-blind, randomized, parallel, placebo-controlled trial.

    PubMed

    Kumar, Ashok; Begum, Nargis; Prasad, Sudha; Aggarwal, Sarita; Sharma, Shashi

    2014-11-01

    To study the impact of administration of dydrogesterone in early pregnancy on pregnancy outcome and its correlation with Th1 and Th2 cytokine levels. Double-blind, randomized, placebo-controlled study. A medical college and its associated hospital. Women with either: [1] a history of idiopathic recurrent pregnancy loss (RPL), in either a dydrogesterone group or a placebo group, or [2] no history of miscarriage. Dydrogesterone 20 mg/day from confirmation of pregnancy to 20 weeks of gestation. Occurrence of another pregnancy loss and concentrations of T-helper (Th)1 (interferon-γ and tumor necrosis factor-α) and Th2 (interleukin (IL)-4 and IL-10) cytokines in serum at recruitment (4-8 weeks of gestation) and at abortion or 20 weeks of gestation, using commercially available ELISA kits. Occurrence of another abortion after 3 consecutive abortions was significantly higher (29 of 173; 16.76%) in women with RPL compared with healthy pregnant controls (6 of 174; 3.45%). Risk of occurrence of miscarriage after 3 abortions was 2.4 times higher in the placebo group vs. the treatment group (risk ratio=2.4, 95% CI=1.3-5.9). Mean gestational age at delivery (excluding those aborted before 20 weeks of gestation) increased significantly in the dydrogesterone group (38.01±1.96 weeks) compared with the placebo group (37.23±2.41 weeks). Baby weight was significantly lower in the placebo group (2421.4±321.6 g) compared with the healthy pregnant controls (2545.3±554.3 g). At recruitment, serum IL-4 and tumor necrosis factor-α levels were significantly lower in the RPL group compared with the healthy pregnant controls. However, serum interferon-γ level was significantly higher in the RPL group (8.87±0.72 pg/mL) compared with the healthy pregnant controls (8.08±1.27 pg/mL). The present study supports the use of dydrogesterone in women with recurrent abortions to improve pregnancy outcome, such as a reduction in abortions and improved gestational age and baby weight at delivery

  4. Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: first results of ETAC. Early Treatment of the Atopic Child.

    PubMed

    1998-08-01

    There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (> or = 30 kU/l) or specific IgE (> or = 0.35 kUA/l) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the

  5. Explorative Placebo-Controlled Double-Blind Intervention Study with Low Doses of Inhaled Δ9-Tetrahydrocannabinol and Cannabidiol Reveals No Effect on Sweet Taste Intensity Perception and Liking in Humans.

    PubMed

    de Bruijn, Suzanne E M; de Graaf, Cees; Witkamp, Renger F; Jager, Gerry

    2017-01-01

    Introduction: The endocannabinoid system (ECS) plays an important role in food reward. For example, in humans, liking of palatable foods is assumed to be modulated by endocannabinoid activity. Studies in rodents suggest that the ECS also plays a role in sweet taste intensity perception, but it is unknown to what extent this can be extrapolated to humans. Therefore, this study aimed at elucidating whether Δ9-tetrahydrocannabinol (THC) or cannabidiol (CBD) affects sweet taste intensity perception and liking in humans, potentially resulting in alterations in food preferences. Materials and Methods: In a randomized placebo-controlled, double-blind crossover study, 10 healthy males participated in three test sessions that were 2 weeks apart. During the test sessions, participants received THC-rich, CBD-rich, or placebo Cannabis by inhalation divided over two doses (4 + 1 mg THC; 25 + 10 mg CBD). Participants tasted seven chocolate milk-like drinks that differed in sugar concentration and they rated sweet taste intensity and liking of the drinks. They were then asked to rank the seven drinks according to how much they liked the drinks and were offered ad libitum access to their favorite drink. In addition, they completed a computerized food preference task and completed an appetite questionnaire at the start, midway, and end of the test sessions. Results: Inhalation of the Cannabis preparations did not affect sweet taste intensity perception and liking, ranking order, or ad libitum consumption of the favorite drink. In addition, food preferences were not influenced by the interventions. Reported fullness was lower, whereas desire to eat was higher throughout the THC compared to the CBD condition. Conclusions: These results suggest that administration of Cannabis preparations at the low doses tested does not affect sweet taste intensity perception and liking, nor does it influence food preferences in humans.

  6. Kv7.3 Compound Heterozygous Variants in Early Onset Encephalopathy Reveal Additive Contribution of C-Terminal Residues to PIP2-Dependent K+ Channel Gating.

    PubMed

    Ambrosino, Paolo; Freri, Elena; Castellotti, Barbara; Soldovieri, Maria Virginia; Mosca, Ilaria; Manocchio, Laura; Gellera, Cinzia; Canafoglia, Laura; Franceschetti, Silvana; Salis, Barbara; Iraci, Nunzio; Miceli, Francesco; Ragona, Francesca; Granata, Tiziana; DiFrancesco, Jacopo C; Taglialatela, Maurizio

    2018-01-30

    Over one hundred mutations in the Kv7.2 (KCNQ2) gene encoding for phosphatidylinositol 4,5-bisphosphate (PIP 2 )-sensitive voltage-gated K + channel subunits have been identified in early-onset epilepsies with wide phenotypic variability. By contrast, only few mutations in the closely related Kv7.3 (KCNQ3) gene have been reported, mostly associated with typical benign familial neonatal seizures (BFNS). We herein describe a patient affected by early onset epileptic encephalopathy (EOEE) carrying two Kv7.3 missense mutations (p.Val359Leu/V359L and p.Asp542Asn/D542N) in compound heterozygosis, each inherited from an asymptomatic parent. Patch-clamp recordings from transiently transfected CHO cells showed that, when incorporated in physiologically relevant Kv7.2 + Kv7.3 heteromeric channels, expression of Kv7.3 V359L or Kv7.3 D542N subunits failed to affect current density, whereas a significant decrease was instead observed when these mutant subunits were both simultaneously present. Modeling and functional experiments revealed that each variant decreased PIP 2 -dependent current regulation, with additive effects when the two were co-expressed. Moreover, expression of Kv7.2 subunits carrying the D535N variant previously described in three sporadic EOEE cases prompted functional changes more dramatic when compared to those of the corresponding D542N variant in Kv7.3, but similar to those observed when both Kv7.3 V359L and Kv7.3 D542N subunits were expressed together. Finally, the Kv7 activator retigabine restored channel dysfunction induced by each Kv7.2 or Kv7.3 variant(s). These results provide a plausible molecular explanation for the apparent recessive inheritance of the phenotype in the family investigated, and a rational basis for personalized therapy with Kv7 channel activators in EOEE patients carrying loss-of-function mutations in Kv7.2 or Kv7.3.

  7. The Complicated Realities of Whiteness: From Color Blind to Racially Cognizant

    ERIC Educational Resources Information Center

    Reason, Robert D.; Evans, Nancy J.

    2007-01-01

    This chapter examines color-blind campuses that perpetuate White transparency and racially cognizant environments that reveal and challenge notions of color blindness. Recommendations are offered to help White students respond to the realities of Whiteness and move beyond color-blind racism.

  8. Global transcriptome analysis of grapevine (Vitis vinifera L.) leaves under salt stress reveals differential response at early and late stages of stress in table grape cv. Thompson Seedless.

    PubMed

    Upadhyay, Anuradha; Gaonkar, Tulsi; Upadhyay, Ajay Kumar; Jogaiah, Satisha; Shinde, Manisha P; Kadoo, Narendra Y; Gupta, Vidya S

    2018-05-31

    Among the different abiotic stresses, salt stress has a significant effect on the growth and yield of grapevine (Vitis vinifera L.). In this study, we employed RNA sequence based transcriptome analysis to study salinity stress response in grape variety Thompson Seedless. Salt stress adversely affected the growth related and physiological parameters and the effect on physiological parameters was significant within 10 days of stress imposition. A total of 343 genes were differentially expressed in response to salt stress. Among the differentially expressed genes (DEGs) only 42 genes were common at early and late stages of stress. The gene enrichment analysis revealed that GO terms related to transcription factors were over-represented. Among the DEGs, 52 were transcription factors belonging to WRKY, EREB, MYB, NAC and bHLH families. Salt stress significantly affected several pathways like metabolic pathways, biosynthesis of secondary metabolites, membrane transport development related pathways etc. 343 DEGs were distributed on all the 19 chromosomes, however clustered regions of DEGs were present on chromosomes 2, 5, 6 and 12 suggesting probable QTLs for imparting tolerance to salt and other abiotic stresses. Real-time PCR of selected genes in control and treated samples of grafted and own root vines demonstrated that rootstock influenced expression of salt stress responsive genes. Microsatellite regions were identified in ten selected salt responsive genes and highly polymorphic markers were identified using fifteen grape genotypes. This information will be useful for the identification of key genes involved in salt stress tolerance in grape. The identified DEGs could also be useful for genome wide analysis for the identification of polymorphic markers for their subsequent use in molecular breeding for developing salt tolerant grape genotypes. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  9. Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL)

    PubMed Central

    Preston, Ioana R.; Roberts, Kari E.; Miller, Dave P.; Sen, Ginny P.; Selej, Mona; Benton, Wade W.; Hill, Nicholas S.

    2015-01-01

    Background— Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH. Methods and Results— Patients who initiated warfarin on study (n=187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from the time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison with warfarin-naïve patients. Conclusions— No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214. PMID:26510696

  10. Mass Cytometry Analysis Reveals the Landscape and Dynamics of CD32a+ CD4+ T Cells From Early HIV Infection to Effective cART.

    PubMed

    Coindre, Sixtine; Tchitchek, Nicolas; Alaoui, Lamine; Vaslin, Bruno; Bourgeois, Christine; Goujard, Cecile; Avettand-Fenoel, Veronique; Lecuroux, Camille; Bruhns, Pierre; Le Grand, Roger; Beignon, Anne-Sophie; Lambotte, Olivier; Favier, Benoit

    2018-01-01

    CD32a has been proposed as a specific marker of latently HIV-infected CD4 + T cells. However, CD32a was recently found to be expressed on CD4 + T cells of healthy donors, leading to controversy on the relevance of this marker in HIV persistence. Here, we used mass cytometry to characterize the landscape and variation in the abundance of CD32a + CD4 + T cells during HIV infection. To this end, we analyzed CD32a + CD4 + T cells in primary HIV infection before and after effective combination antiretroviral therapy (cART) and in healthy donors. We found that CD32a + CD4 + T cells include heterogeneous subsets that are differentially affected by HIV infection. Our analysis revealed that naive ( N ), central memory ( CM ), and effector/memory ( Eff/Mem ) CD32a + CD4 + T-cell clusters that co-express LILRA2- and CD64-activating receptors were more abundant in primary HIV infection and cART stages. Conversely, LILRA2 - CD32a + CD4 + T-cell clusters of either the T N , T CM , or T Eff/Mem phenotype were more abundant in healthy individuals. Finally, an activated CD32a + CD4 + T Eff/Mem cell cluster co-expressing LILRA2, CD57, and NKG2C was more abundant in all HIV stages, particularly during primary HIV infection. Overall, our data show that multiple abundance modifications of CD32a + CD4 + T-cell subsets occur in the early phase of HIV infection, and some of which are conserved after effective cART. Our study brings a better comprehension of the relationship between CD32a expression and CD4 + T cells during HIV infection.

  11. Ancient DNA analyses of early archaeological sites in New Zealand reveal extreme exploitation of moa (Aves: Dinornithiformes) at all life stages

    NASA Astrophysics Data System (ADS)

    Oskam, Charlotte L.; Allentoft, Morten E.; Walter, Richard; Scofield, R. Paul; Haile, James; Holdaway, Richard N.; Bunce, Michael; Jacomb, Chris

    2012-10-01

    The human colonisation of New Zealand in the late thirteenth century AD led to catastrophic impacts on the local biota and is among the most compelling examples of human over-exploitation of native fauna, including megafauna. Nearly half of the species in New Zealand' s pre-human avifauna are now extinct, including all nine species of large, flightless moa (Aves: Dinornithiformes). The abundance of moa in early archaeological sites demonstrates the significance of these megaherbivores in the diet of the first New Zealanders. Combining moa assemblage data, based on DNA identification of eggshell and bone, with morphological identification of bone (literature and museum catalogued specimens), we present the most comprehensive audit of moa to date from several significant 13th-15th century AD archaeological deposits across the east coast of the South Island. Mitochondrial DNA (mtDNA) was amplified from 251 of 323 (78%) eggshell fragments and 22 of 27 (88%) bone samples, and the analyses revealed the presence of four moa species: Anomalopteryx didiformis; Dinornis robustus; Emeus crassus and Euryapteryx curtus. The mtDNA, along with polymorphic microsatellite markers, enabled an estimate of the minimum number of individual eggs consumed at each site. Remarkably, in one deposit over 50 individual eggs were identified - a number that likely represents a considerable proportion of the total reproductive output of moa in the area and emphasises that human predation of all life stages of moa was intense. Molecular sexing was conducted on bones (n = 11). Contrary to previous ancient DNA studies from natural sites that consistently report an excess of female moa, we observed an excess of males (2.7:1), suggestive that males were preferential targets. This could be related to different behaviour between the two highly size-dimorphic sexes in moa. Lastly, we investigated the moa species from recovered skeletal and eggshell remains from seven Wairau Bar burials, and identified

  12. Gene Expression Analysis of Early Stage Endometrial Cancers Reveals Unique Transcripts Associated with Grade and Histology but Not Depth of Invasion

    PubMed Central

    Risinger, John I.; Allard, Jay; Chandran, Uma; Day, Roger; Chandramouli, Gadisetti V. R.; Miller, Caela; Zahn, Christopher; Oliver, Julie; Litzi, Tracy; Marcus, Charlotte; Dubil, Elizabeth; Byrd, Kevin; Cassablanca, Yovanni; Becich, Michael; Berchuck, Andrew; Darcy, Kathleen M.; Hamilton, Chad A.; Conrads, Thomas P.; Maxwell, G. Larry

    2013-01-01

    Endometrial cancer is the most common gynecologic malignancy in the United States but it remains poorly understood at the molecular level. This investigation was conducted to specifically assess whether gene expression changes underlie the clinical and pathologic factors traditionally used for determining treatment regimens in women with stage I endometrial cancer. These include the effect of tumor grade, depth of myometrial invasion and histotype. We utilized oligonucleotide microarrays to assess the transcript expression profile in epithelial glandular cells laser microdissected from 79 endometrioid and 12 serous stage I endometrial cancers with a heterogeneous distribution of grade and depth of myometrial invasion, along with 12 normal post-menopausal endometrial samples. Unsupervised multidimensional scaling analyses revealed that serous and endometrioid stage I cancers have similar transcript expression patterns when compared to normal controls where 900 transcripts were identified to be differentially expressed by at least fourfold (univariate t-test, p < 0.001) between the cancers and normal endometrium. This analysis also identified transcript expression differences between serous and endometrioid cancers and tumor grade, but no apparent differences were identified as a function of depth of myometrial invasion. Four genes were validated by quantitative PCR on an independent set of cancer and normal endometrium samples. These findings indicate that unique gene expression profiles are associated with histologic type and grade, but not myometrial invasion among early stage endometrial cancers. These data provide a comprehensive perspective on the molecular alterations associated with stage I endometrial cancer, particularly those subtypes that have the worst prognosis. PMID:23785665

  13. Analysis of a vinculin homolog in a sponge (phylum Porifera) reveals that vertebrate-like cell adhesions emerged early in animal evolution.

    PubMed

    Miller, Phillip W; Pokutta, Sabine; Mitchell, Jennyfer M; Chodaparambil, Jayanth V; Clarke, D Nathaniel; Nelson, William; Weis, William I; Nichols, Scott A

    2018-06-07

    The evolution of cell adhesion mechanisms in animals facilitated the assembly of organized multicellular tissues. Studies in traditional animal models have revealed two predominant adhesion structures, the adherens junction (AJ) and focal adhesions (FAs), which are involved in the attachment of neighboring cells to each other and to the secreted extracellular matrix (ECM), respectively. The AJ (containing cadherins and catenins) and FAs (comprising integrins, talin, and paxillin) differ in protein composition, but both junctions contain the actin-binding protein vinculin. The near ubiquity of these structures in animals suggests that AJ and FAs evolved early, possibly coincident with multicellularity. However, a challenge to this perspective is that previous studies of sponges-a divergent animal lineage-indicate that their tissues are organized primarily by an alternative, sponge-specific cell adhesion mechanism called "aggregation factor." In this study, we examined the structure, biochemical properties, and tissue localization of a vinculin ortholog in the sponge Oscarella pearsei ( Op ). Our results indicate that Op vinculin localizes to both cell-cell and cell-ECM contacts and has biochemical and structural properties similar to those of vertebrate vinculin. We propose that Op vinculin played a role in cell adhesion and tissue organization in the last common ancestor of sponges and other animals. These findings provide compelling evidence that sponge tissues are indeed organized like epithelia in other animals and support the notion that AJ- and FA-like structures extend to the earliest periods of animal evolution. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL).

    PubMed

    Preston, Ioana R; Roberts, Kari E; Miller, Dave P; Sen, Ginny P; Selej, Mona; Benton, Wade W; Hill, Nicholas S; Farber, Harrison W

    2015-12-22

    Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH. Patients who initiated warfarin on study (n=187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from the time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison with warfarin-naïve patients. No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214. © 2015 The Authors.

  15. Enhanced heat discrimination in congenital blindness.

    PubMed

    Slimani, Hocine; Ptito, Maurice; Kupers, Ron

    2015-04-15

    There is substantial evidence that congenitally blind individuals perform better than normally sighted controls in a variety of auditory, tactile and olfactory discrimination tasks. However, little is known about the capacity of blind individuals to make fine discriminatory judgments in the thermal domain. We therefore compared the capacity to detect small temperature increases in innocuous heat in a group of 12 congenitally blind and 12 age and sex-matched normally sighted participants. In addition, we also tested for group differences in the effects of spatial summation on temperature discrimination. Thermal stimuli were delivered with either a 2.56 or 9 cm(2) Peltier-based thermode. We applied for 5-8s lasting non-painful thermal stimuli to the forearm and asked participants to detect small increments in temperature (ΔT = 0.4, 0.8, 1.2 or 1.6°C) that occurred at random time intervals. Blank trials (ΔT = 0°C) were also included to test for false positive responses. We used signal detection theory model to analyze the data. Our data revealed that blind participants have a higher accuracy than the sighted (d': Blind=2.4 ± 1.0, Sighted=1.8 ± 0.7, p=0.025), regardless of the size of the stimulated skin surface or magnitude of the temperature shift. Increasing the size of the stimulated skin area increased the response criterion in the blind (p=0.022) but not in the sighted. Together, these findings show that congenitally blind individuals have enhanced temperature discrimination accuracy and are more susceptible to spatial summation of heat. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Relationship between the Development of Language and Thought in Young Blind Children.

    ERIC Educational Resources Information Center

    Bigelow, A.

    1990-01-01

    The relationship between the development of object permanence and early words was studied in three young boys, two totally blind from birth and one severely visually impaired. Subjects acquired early words within the age range for sighted children but their word usage was different. The two blind children were delayed in their development of…

  17. Enhanced Chemosensory Detection of Negative Emotions in Congenital Blindness

    PubMed Central

    Iversen, Katrine D.; Ptito, Maurice; Møller, Per; Kupers, Ron

    2015-01-01

    It is generally acknowledged that congenitally blind individuals develop superior sensory abilities in order to compensate for their lack of vision. Substantial research has been done on somatosensory and auditory sensory information processing of the blind. However, relatively little information is available about compensatory plasticity in the olfactory domain. Although previous studies indicate that blind individuals have superior olfactory abilities, no studies so far have investigated their sense of smell in relation to social and affective communication. The current study compares congenitally blind and normal sighted individuals in their ability to discriminate and identify emotions from body odours. A group of 14 congenitally blind and 14 age- and sex-matched sighted control subjects participated in the study. We compared participants' abilities to detect and identify by smelling sweat from donors who had been watching excerpts from emotional movies showing amusement, fear, disgust, or sexual arousal. Our results show that congenitally blind subjects outperformed sighted controls in identifying fear from male donors. In addition, there was a strong tendency that blind individuals were also better in detecting disgust. Our findings reveal that congenitally blind individuals are better at identifying ecologically important emotions and provide new insights into the mechanisms of social and affective communication in blindness. PMID:25878902

  18. Early Detection of Eruptive Dykes Revealed by Normalized Difference Vegetation Index (NDVI) on Nyiragongo and Etna Volcanoes: Implications for Dyke Wedge Emplacement, Monitoring, and Risk Assessment.

    NASA Astrophysics Data System (ADS)

    Komorowski, J.; Houlié, N.; Kasereka, C. M.; Ciraba, H.

    2006-12-01

    Flank-fissure eruptions involve lateral injection and propagation of magma in a volcanic edifice along pre- existing fractures in the direction of a volcanic rift zone (VRZ) where magma intrusion and lava flow production are concentrated over time. Gradual dyke wedge emplacement on volcano flanks and in VRZ's does not necessarily trigger large amplitude deformation signals susceptible to be recorded months or even years before the actual eruption. We show that active and potentially eruptive areas in a VRZ can be detected up to 2 years before the arrival to the surface of the final eruptive dyke and venting of lava flows by processing satellite images applying a Normalized Difference Vegetation Index (NDVI) algorithm. A positive NDVI anomaly is indicative of excessive photosynthetic plant activity. A posteriori analysis of satellite images reveal that a high- NDVI linear anomaly was apparent in vegetated areas of VRZ's on Etna from 2000 to 2002 and on Nyiragongo in June 2001, several months to years before eruptive fractures formed directly above the NDVI anomaly. We propose that the observed NDVI linear anomalies are the signature of the integrated physico-chemical effects (increased heat and CO2 flux, H2O condensation) caused by the structurally-controlled progressive injection and propagation, in a VRZ and a few months to years before the eruption, of a series of dykes (dyke wedge) that did not reach the surface. We focus of Nyiragongo volcano where historical flank-fissure eruptions from lava lake drainage in 1977 and 2002 show a link with tectonics of the Kivu rift (western branch of the East African Rift System). In 2002, dykes were injected in the southern VRZ bounded by Kivu rift normal faults and propagated over 14 km producing lava flows that caused widespread destruction in the city of Goma. Data from Nyiragongo suggest that as a dyke wedge is formed and repeatedly reactivated, final eruptive dykes can be injected easily and can propagate rapidly further

  19. The complete chloroplast DNA sequence of the green alga Oltmannsiellopsis viridis reveals a distinctive quadripartite architecture in the chloroplast genome of early diverging ulvophytes

    PubMed Central

    Pombert, Jean-François; Lemieux, Claude; Turmel, Monique

    2006-01-01

    Background The phylum Chlorophyta contains the majority of the green algae and is divided into four classes. The basal position of the Prasinophyceae has been well documented, but the divergence order of the Ulvophyceae, Trebouxiophyceae and Chlorophyceae is currently debated. The four complete chloroplast DNA (cpDNA) sequences presently available for representatives of these classes have revealed extensive variability in overall structure, gene content, intron composition and gene order. The chloroplast genome of Pseudendoclonium (Ulvophyceae), in particular, is characterized by an atypical quadripartite architecture that deviates from the ancestral type by a large inverted repeat (IR) featuring an inverted rRNA operon and a small single-copy (SSC) region containing 14 genes normally found in the large single-copy (LSC) region. To gain insights into the nature of the events that led to the reorganization of the chloroplast genome in the Ulvophyceae, we have determined the complete cpDNA sequence of Oltmannsiellopsis viridis, a representative of a distinct, early diverging lineage. Results The 151,933 bp IR-containing genome of Oltmannsiellopsis differs considerably from Pseudendoclonium and other chlorophyte cpDNAs in intron content and gene order, but shares close similarities with its ulvophyte homologue at the levels of quadripartite architecture, gene content and gene density. Oltmannsiellopsis cpDNA encodes 105 genes, contains five group I introns, and features many short dispersed repeats. As in Pseudendoclonium cpDNA, the rRNA genes in the IR are transcribed toward the single copy region featuring the genes typically found in the ancestral LSC region, and the opposite single copy region harbours genes characteristic of both the ancestral SSC and LSC regions. The 52 genes that were transferred from the ancestral LSC to SSC region include 12 of those observed in Pseudendoclonium cpDNA. Surprisingly, the overall gene organization of Oltmannsiellopsis cp

  20. Blindness to Curvature and Blindness to Illusory Curvature.

    PubMed

    Bertamini, Marco; Kitaoka, Akiyoshi

    2018-01-01

    We compare two versions of two known phenomena, the Curvature blindness and the Kite mesh illusions, to highlight how similar manipulations lead to blindness to curvature and blindness to illusory curvature, respectively. The critical factor is a change in luminance polarity; this factor interferes with the computation of curvature along the contour, for both real and illusory curvature.

  1. Visual impairment and blindness in Hungary.

    PubMed

    Szabó, Dorottya; Sándor, Gábor László; Tóth, Gábor; Pék, Anita; Lukács, Regina; Szalai, Irén; Tóth, Georgina Zsófia; Papp, András; Nagy, Zoltán Zsolt; Limburg, Hans; Németh, János

    2018-03-01

    The aim of this study was to estimate the prevalence and causes of blindness, severe visual impairment (SVI), moderate visual impairment (MVI), and early visual impairment (EVI) and its causes in an established market economy of Europe. A cross-sectional population-based survey. A sample size of 3675 was calculated using the standard Rapid Assessment of Avoidable Blindness (RAAB) software in Hungary. A total of 105 clusters of 35 people aged 50 years or older were randomly selected with probability proportionate to size by the Hungarian Central Statistical Office. Households within the clusters were selected using compact segment sampling. Visual acuity (VA) was assessed with a Snellen tumbling E-chart with or without a pinhole in the households. The adjusted prevalences of bilateral blindness, SVI, MVI and EVI were 0.9% (95% CI: 0.6-1.2), 0.5% (95% CI: 0.2-0.7), 5.1% (95% CI: 4.3-5.9) and 6.9% (95% CI: 5.9-7.9), respectively. The major causes of blindness in Hungary were age-related macular degeneration (AMD; 27.3%) and other posterior segment diseases (27.3%), cataract (21.2%) and glaucoma (12.1%). Cataract was the main cause of SVI, MVI and EVI. Cataract surgical coverage (CSC) was 90.7%. Of all bilateral blindness in Hungary, 45.5% was considered avoidable. This study proved that RAAB methodology can be successfully conducted in industrialized countries, which often lack reliable epidemiologic data. The prevalence of blindness was relatively low, with AMD and other posterior segment diseases being the leading causes, and cataract is still a significant cause of visual impairment. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  2. Blinded by Science.

    ERIC Educational Resources Information Center

    Snyder, Tom

    1994-01-01

    Huge infusion of technology is coming into education; nothing can stop it, because so much money is involved. With computer marketers in driver seat instead of teachers, schools risk being blinded by science. Vendors have coopted progressive education buzzwords, including "frontal teaching,""linear thinking," and "computer…

  3. Culture and Change Blindness

    ERIC Educational Resources Information Center

    Masuda, Takahiko; Nisbett, Richard E.

    2006-01-01

    Research on perception and cognition suggests that whereas East Asians view the world holistically, attending to the entire field and relations among objects, Westerners view the world analytically, focusing on the attributes of salient objects. These propositions were examined in the change-blindness paradigm. Research in that paradigm finds…

  4. Homer: The Blind Bard

    ERIC Educational Resources Information Center

    Doorley, Rachelle; King, Judith

    2005-01-01

    This article describes notable cultural, historical, and artistic elements emanating from sculptures originating in ancient Greece. The "blind bard" and its connection to the legendary Greek poet, Homer; Homer's impact on literary history; trends among Roman sculptures; and Roman replication of Greek art are described. Questions to…

  5. Universal Blind Quantum Computation

    NASA Astrophysics Data System (ADS)

    Fitzsimons, Joseph; Kashefi, Elham

    2012-02-01

    Blind Quantum Computing (BQC) allows a client to have a server carry out a quantum computation for them such that the client's inputs, outputs and computation remain private. Recently we proposed a universal unconditionally secure BQC scheme, based on the conceptual framework of the measurement-based quantum computing model, where the client only needs to be able to prepare single qubits in separable states randomly chosen from a finite set and send them to the server, who has the balance of the required quantum computational resources. Here we present a refinement of the scheme which vastly expands the class of quantum circuits which can be directly implemented as a blind computation, by introducing a new class of resource states which we term dotted-complete graph states and expanding the set of single qubit states the client is required to prepare. These two modifications significantly simplify the overall protocol and remove the previously present restriction that only nearest-neighbor circuits could be implemented as blind computations directly. As an added benefit, the refined protocol admits a substantially more intuitive and simplified verification mechanism, allowing the correctness of a blind computation to be verified with arbitrarily small probability of error.

  6. Blindness in the Toybox

    ERIC Educational Resources Information Center

    Swartz, Edward M.

    1973-01-01

    The author proposes that toys which have been shown to cause blindness (such as dart guns, bows and arrows, peashooters, air guns, and slingshots) be banned, and suggests that government regulatory agencies and the toy industry have been lax in acting on their expressed concern for safety. (DB)

  7. Enteral nutrition with eicosapentaenoic acid, γ-linolenic acid and antioxidants in the early treatment of sepsis: results from a multicenter, prospective, randomized, double-blinded, controlled study: the INTERSEPT Study

    PubMed Central

    2011-01-01

    Introduction Enteral nutrition (EN) with eicosapentaenoic acid (EPA)/γ-linolenic acid (GLA) is recommended for mechanically ventilated patients with severe lung injury. EPA/GLA has anti-inflammatory benefits, as evidenced by its association with reduction in pulmonary inflammation, improvement in oxygenation and improved clinical outcomes in patients with severe forms of acute lung injury. This study was a prospective, multicenter, randomized, double-blinded, controlled trial designed to investigate whether EPA/GLA could have an effective role in the treatment of patients with early sepsis (systemic inflammatory response syndrome with confirmed or presumed infection and without any organ dysfunction) by reducing the progression of the disease to severe sepsis (sepsis associated with at least one organ failure) or septic shock (sepsis associated with hypotension despite adequate fluid resuscitation). Secondary outcomes included the development of individual organ failure, increased ICU and hospital length of stay, need for mechanical ventilation and 28-day all-cause mortality. Methods Randomization was concealed, and patients were allocated to receive, for seven days, either an EPA/GLA diet or an isocaloric, isonitrogenous control diet not enhanced with lipids. Patients were continuously tube-fed at a minimum of 75% of basal energy expenditure × 1.3. To evaluate the progression to severe sepsis and/or septic shock, daily screening for individual organ failure was performed. All clinical outcomes were recorded during a 28-day follow-up period. Results A total of 115 patients in the early stages of sepsis requiring EN were included, among whom 106 were considered evaluable. Intention-to-treat (ITT) analysis demonstrated that patients fed the EPA/GLA diet developed less severe sepsis and/or septic shock than patients fed the control diet (26.3% versus 50%, respectively; P = 0.0259), with similar results observed for the evaluable patients (26.4% versus 50

  8. Efficient universal blind quantum computation.

    PubMed

    Giovannetti, Vittorio; Maccone, Lorenzo; Morimae, Tomoyuki; Rudolph, Terry G

    2013-12-06

    We give a cheat sensitive protocol for blind universal quantum computation that is efficient in terms of computational and communication resources: it allows one party to perform an arbitrary computation on a second party's quantum computer without revealing either which computation is performed, or its input and output. The first party's computational capabilities can be extremely limited: she must only be able to create and measure single-qubit superposition states. The second party is not required to use measurement-based quantum computation. The protocol requires the (optimal) exchange of O(Jlog2(N)) single-qubit states, where J is the computational depth and N is the number of qubits needed for the computation.

  9. Blindness in designing intelligent systems

    NASA Technical Reports Server (NTRS)

    Denning, Peter J.

    1988-01-01

    New investigations of the foundations of artificial intelligence are challenging the hypothesis that problem solving is the cornerstone of intelligence. New distinctions among three domains of concern for humans--description, action, and commitment--have revealed that the design process for programmable machines, such as expert systems, is based on descriptions of actions and induces blindness to nonanalytic action and commitment. Design processes focusing in the domain of description are likely to yield programs like burearcracies: rigid, obtuse, impersonal, and unable to adapt to changing circumstances. Systems that learn from their past actions, and systems that organize information for interpretation by human experts, are more likely to be successful in areas where expert systems have failed.

  10. Humanizing Blindness through Public Education.

    ERIC Educational Resources Information Center

    Augusto, C. R.; McGraw, J. M.

    1990-01-01

    Public attitudes toward blindness are shaped by limited contacts with visually impaired people and unrealistic portrayals of blind people in the media. Proactive efforts including national and local public education programs are needed to change stereotyped thinking, humanize blindness, and lead to greater opportunities for fuller participation in…

  11. Programs for the Deaf Blind.

    ERIC Educational Resources Information Center

    American Annals of the Deaf, 1987

    1987-01-01

    The directory lists 30 programs for deaf-blind children and youth, the 10 regional offices of the Helen Keller National Center for Deaf-Blind Youths and Adults, and five programs for training teachers of the deaf-blind. Provided for each program is address, director's name, and phone number. (DB)

  12. When Emotion Blinds: A Spatiotemporal Competition Account of Emotion-Induced Blindness

    PubMed Central

    Wang, Lingling; Kennedy, Briana L.; Most, Steven B.

    2012-01-01

    Emotional visual scenes are such powerful attractors of attention that they can disrupt perception of other stimuli that appear soon afterward, an effect known as emotion-induced blindness. What mechanisms underlie this impact of emotion on perception? Evidence suggests that emotion-induced blindness may be distinguishable from closely related phenomena such as the orienting of spatial attention to emotional stimuli or the central resource bottlenecks commonly associated with the attentional blink. Instead, we suggest that emotion-induced blindness reflects relatively early competition between targets and emotional distractors, where spontaneous prioritization of emotional stimuli leads to suppression of competing perceptual representations potentially linked to an overlapping point in time and space. PMID:23162497

  13. Vision after 53 years of blindness.

    PubMed

    Sikl, Radovan; Simecček, Michal; Porubanová-Norquist, Michaela; Bezdíček, Ondřej; Kremláček, Jan; Stodůlka, Pavel; Fine, Ione; Ostrovsky, Yuri

    2013-01-01

    Several studies have shown that visual recovery after blindness that occurs early in life is never complete. The current study investigated whether an extremely long period of blindness might also cause a permanent impairment of visual performance, even in a case of adult-onset blindness. We examined KP, a 71-year-old man who underwent a successful sight-restoring operation after 53 years of blindness. A set of psychophysical tests designed to assess KP's face perception, object recognition, and visual space perception abilities were conducted six months and eight months after the surgery. The results demonstrate that regardless of a lengthy period of normal vision and rich pre-accident perceptual experience, KP did not fully integrate this experience, and his visual performance remained greatly compromised. This was particularly evident when the tasks targeted finer levels of perceptual processing. In addition to the decreased robustness of his memory representations, which was hypothesized as the main factor determining visual impairment, other factors that may have affected KP's performance were considered, including compromised visual functions, problems with perceptual organization, deficits in the simultaneous processing of visual information, and reduced cognitive abilities.

  14. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial.

    PubMed

    2017-05-27

    Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10

  15. Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial.

    PubMed

    von Minckwitz, Gunter; Colleoni, Marco; Kolberg, Hans-Christian; Morales, Serafin; Santi, Patricia; Tomasevic, Zorica; Zhang, Nan; Hanes, Vladimir

    2018-06-04

    ABP 980 (Amgen Inc, Thousand Oaks, CA, USA) is a biosimilar of trastuzumab, with analytical, functional, and pharmacokinetic similarities. We compared the clinical safety and efficacy of ABP 980 with that of trastuzumab in women with HER2-positive early breast cancer. We did a randomised, multicentre, double-blind, active-controlled equivalence trial at 97 study centres in 20 countries, mainly in Europe and South America. Eligible women were aged 18 years or older, had histologically confirmed HER2-positive invasive early breast cancer, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and were planning to have surgical resection of the breast tumour with sentinel or axillary lymph node dissection and neoadjuvant chemotherapy. After four cycles of run-in anthracycline-based chemotherapy, patients were assigned 1:1 to receive ABP 980 or trastuzumab with a permuted block design (blocks of four) computer-generated randomisation schedule. Patients received neoadjuvant therapy with a loading dose (8 mg/kg) of ABP 980 or trastuzumab plus paclitaxel 175 mg/m 2 in a 90 min intravenous infusion, followed by three cycles of 6 mg/kg intravenous ABP 980 or trastuzumab plus paclitaxel 175 mg/m 2 every 3 weeks in 30 min intravenous infusions (or 80 mg/m 2 paclitaxel once per week for 12 cycles if that was the local standard of care). Randomisation was stratified by T stage, node status, hormone receptor status, planned paclitaxel dosing schedule, and geographical region. Surgery was completed 3-7 weeks after the last dose of neoadjuvant treatment, after which adjuvant treatment with ABP 980 or trastuzumab was given every 3 weeks for up to 1 year after the first dose in the study. Patients had been randomly assigned at baseline to continue APB 980, continue trastuzumab, or switch from trastuzumab to APB 980 as their adjuvant treatment. The co-primary efficacy endpoints were risk difference and risk ratio (RR) of pathological complete response in breast

  16. The ATLAS3D project - IX. The merger origin of a fast- and a slow-rotating early-type galaxy revealed with deep optical imaging: first results

    NASA Astrophysics Data System (ADS)

    Duc, Pierre-Alain; Cuillandre, Jean-Charles; Serra, Paolo; Michel-Dansac, Leo; Ferriere, Etienne; Alatalo, Katherine; Blitz, Leo; Bois, Maxime; Bournaud, Frédéric; Bureau, Martin; Cappellari, Michele; Davies, Roger L.; Davis, Timothy A.; de Zeeuw, P. T.; Emsellem, Eric; Khochfar, Sadegh; Krajnović, Davor; Kuntschner, Harald; Lablanche, Pierre-Yves; McDermid, Richard M.; Morganti, Raffaella; Naab, Thorsten; Oosterloo, Tom; Sarzi, Marc; Scott, Nicholas; Weijmans, Anne-Marie; Young, Lisa M.

    2011-10-01

    The mass assembly of galaxies leaves imprints in their outskirts, such as shells and tidal tails. The frequency and properties of such fine structures depend on the main acting mechanisms - secular evolution, minor or major mergers - and on the age of the last substantial accretion event. We use this to constrain the mass assembly history of two apparently relaxed nearby early-type galaxies (ETGs) selected from the ATLAS3D sample, NGC 680 and 5557. Our ultra-deep optical images obtained with MegaCam on the Canada-France-Hawaii Telescope reach 29 mag arcsec-2 in the g band. They reveal very low surface brightness (LSB) filamentary structures around these ellipticals. Among them, a gigantic 160 kpc long, narrow, tail east of NGC 5557 hosts three gas-rich star-forming objects, previously detected in H I with the Westerbork Synthesis Radio Telescope and in UV with GALEX. NGC 680 exhibits two major diffuse plumes apparently connected to extended H I tails, as well as a series of arcs and shells. Comparing the outer stellar and gaseous morphology of the two ellipticals with that predicted from models of colliding galaxies, we argue that the LSB features are tidal debris and that each of these two ETGs was assembled during a relatively recent, major wet merger, which most likely occurred after the redshift z ≃ 0.5 epoch. Had these mergers been older, the tidal features should have already fallen back or be destroyed by more recent accretion events. However, the absence of molecular gas and of a prominent young stellar population in the core region of the galaxies indicates that the merger is at least 1-2 Gyr old: the memory of any merger-triggered nuclear starburst has indeed been lost. The star-forming objects found towards the collisional debris of NGC 5557 are then likely tidal dwarf galaxies. Such recycled galaxies here appear to be long-lived and continue to form stars while any star formation activity has stopped in their parent galaxy. The inner kinematics of NGC

  17. Reduced Left Lateralization of Language in Congenitally Blind Individuals.

    PubMed

    Lane, Connor; Kanjlia, Shipra; Richardson, Hilary; Fulton, Anne; Omaki, Akira; Bedny, Marina

    2017-01-01

    Language processing depends on a left-lateralized network of frontotemporal cortical regions. This network is remarkably consistent across individuals and cultures. However, there is also evidence that developmental factors, such as delayed exposure to language, can modify this network. Recently, it has been found that, in congenitally blind individuals, the typical frontotemporal language network expands to include parts of "visual" cortices. Here, we report that blindness is also associated with reduced left lateralization in frontotemporal language areas. We analyzed fMRI data from two samples of congenitally blind adults (n = 19 and n = 13) and one sample of congenitally blind children (n = 20). Laterality indices were computed for sentence comprehension relative to three different control conditions: solving math equations (Experiment 1), a memory task with nonwords (Experiment 2), and a "does this come next?" task with music (Experiment 3). Across experiments and participant samples, the frontotemporal language network was less left-lateralized in congenitally blind than in sighted individuals. Reduction in left lateralization was not related to Braille reading ability or amount of occipital plasticity. Notably, we observed a positive correlation between the lateralization of frontotemporal cortex and that of language-responsive occipital areas in blind individuals. Blind individuals with right-lateralized language responses in frontotemporal cortices also had right-lateralized occipital responses to language. Together, these results reveal a modified neurobiology of language in blindness. Our findings suggest that, despite its usual consistency across people, the neurobiology of language can be modified by nonlinguistic experiences.

  18. Superior Orthonasal but Not Retronasal Olfactory Skills in Congenital Blindness

    PubMed Central

    Gagnon, Lea; Ismaili, Abd Rahman Alaoui; Ptito, Maurice; Kupers, Ron

    2015-01-01

    Sight is undoubtedly important for finding and appreciating food, and cooking. Blind individuals are strongly impaired in finding food, limiting the variety of flavours they are exposed to. We have shown before that compared to sighted controls, congenitally blind individuals have enhanced olfactory but reduced taste perception. In this study we tested the hypothesis that congenitally blind subjects have enhanced orthonasal but not retronasal olfactory skills. Twelve congenitally blind and 14 sighted control subjects, matched in age, gender and body mass index, were asked to identify odours using grocery-available food powders. Results showed that blind subjects were significantly faster and tended to be better at identifying odours presented orthonasally. This was not the case when odorants were presented retronasally. We also found a significant group x route interaction, showing that although both groups performed better for retronasally compared to orthonasally presented odours, this gain was less pronounced for blind subjects. Finally, our data revealed that blind subjects were more familiar with the orthonasal odorants and used the retronasal odorants less often for cooking than their sighted counterparts. These results confirm that orthonasal but not retronasal olfactory perception is enhanced in congenital blindness, a result that is concordant with the reduced food variety exposure in this group. PMID:25822780

  19. Postpartum cortical blindness.

    PubMed

    Faiz, Shakeel Ahmed

    2008-09-01

    A 30-years-old third gravida with previous normal pregnancies and an unremarkable prenatal course had an emergency lower segment caesarean section at a periphery hospital for failure of labour to progress. She developed bilateral cortical blindness immediately after recovery from anesthesia due to cerebral angiopathy shown by CT and MR scan as cortical infarct cerebral angiopathy, which is a rare complication of a normal pregnancy.

  20. Community Structure Analysis of Transcriptional Networks Reveals Distinct Molecular Pathways for Early- and Late-Onset Temporal Lobe Epilepsy with Childhood Febrile Seizures

    PubMed Central

    Moreira-Filho, Carlos Alberto; Bando, Silvia Yumi; Bertonha, Fernanda Bernardi; Iamashita, Priscila; Silva, Filipi Nascimento; Costa, Luciano da Fontoura; Silva, Alexandre Valotta; Castro, Luiz Henrique Martins; Wen, Hung-Tzu

    2015-01-01

    Age at epilepsy onset has a broad impact on brain plasticity and epilepsy pathomechanisms. Prolonged febrile seizures in early childhood (FS) constitute an initial precipitating insult (IPI) commonly associated with mesial temporal lobe epilepsy (MTLE). FS-MTLE patients may have early disease onset, i.e. just after the IPI, in early childhood, or late-onset, ranging from mid-adolescence to early adult life. The mechanisms governing early (E) or late (L) disease onset are largely unknown. In order to unveil the molecular pathways underlying E and L subtypes of FS-MTLE we investigated global gene expression in hippocampal CA3 explants of FS-MTLE patients submitted to hippocampectomy. Gene coexpression networks (GCNs) were obtained for the E and L patient groups. A network-based approach for GCN analysis was employed allowing: i) the visualization and analysis of differentially expressed (DE) and complete (CO) - all valid GO annotated transcripts - GCNs for the E and L groups; ii) the study of interactions between all the system’s constituents based on community detection and coarse-grained community structure methods. We found that the E-DE communities with strongest connection weights harbor highly connected genes mainly related to neural excitability and febrile seizures, whereas in L-DE communities these genes are not only involved in network excitability but also playing roles in other epilepsy-related processes. Inversely, in E-CO the strongly connected communities are related to compensatory pathways (seizure inhibition, neuronal survival and responses to stress conditions) while in L-CO these communities harbor several genes related to pro-epileptic effects, seizure-related mechanisms and vulnerability to epilepsy. These results fit the concept, based on fMRI and behavioral studies, that early onset epilepsies, although impacting more severely the hippocampus, are associated to compensatory mechanisms, while in late MTLE development the brain is less able to

  1. Gene expression profiling reveals different molecular patterns in G-protein coupled receptor signaling pathways between early- and late-onset preeclampsia.

    PubMed

    Liang, Mengmeng; Niu, Jianmin; Zhang, Liang; Deng, Hua; Ma, Jian; Zhou, Weiping; Duan, Dongmei; Zhou, Yuheng; Xu, Huikun; Chen, Longding

    2016-04-01

    Early-onset preeclampsia and late-onset preeclampsia have been regarded as two different phenotypes with heterogeneous manifestations; To gain insights into the pathogenesis of the two traits, we analyzed the gene expression profiles in preeclamptic placentas. A whole genome-wide microarray was used to determine the gene expression profiles in placental tissues from patients with early-onset (n = 7; <34 weeks), and late-onset (n = 8; >36 weeks) preeclampsia and their controls who delivered preterm (n = 5; <34 weeks) or at term (n = 5; >36 weeks). Genes were termed differentially expressed if they showed a fold-change ≥ 2 and q-value < 0.05. Quantitative real-time reverse transcriptase PCR was used to verify the results. Western blotting was performed to verify the expressions of secreted genes at the protein level. Six hundred twenty-seven genes were differentially expressed in early-compared with late-onset preeclampsia (177 genes were up-regulated and 450 were down-regulated). Gene ontology analysis identified significant alterations in several biological processes; the top two were immune response and cell surface receptor linked signal transduction. Among the cell surface receptor linked signal transduction-related, differentially expressed genes, those involved in the G-protein coupled receptor protein signaling pathway were significantly enriched. G-protein coupled receptor signaling pathway related genes, such as GPR124 and MRGPRF, were both found to be down-regulated in early-onset preeclampsia. The results were consistent with those of western blotting that the abundance of GPR124 was lower in early-onset compared with late-onset preeclampsia. The different gene expression profiles reflect the different levels of transcription regulation between the two conditions and supported the hypothesis that they are separate disease entities. Moreover, the G-protein coupled receptor signaling pathway related genes may contribute to the mechanism underlying early

  2. Reinforcement control of severe dysfunctional behavior of blind, multihandicapped students.

    PubMed

    Luiselli, J K; Myles, E; Evans, T P; Boyce, D A

    1985-11-01

    The effectiveness of reinforcement-based programs with blind, multihandicapped students was examined. In Study 1 the aggressive behavior of a deaf/blind adolescent was eliminated through a differential reinforcement of other behavior (DRO) procedure that was combined with a reinforcer cueing technique and brief time-out. In Study 2 DRO was utilized to reduce stereotypic eye-pressing by a young blind child who was also hearing-impaired. Follow-up observations while treatment procedures remained operative revealed maintenance of intervention effects from 1 to 8 months posttreatment.

  3. Psychological and social adjustment to blindness: understanding from two groups of blind people in Ilorin, Nigeria.

    PubMed

    Tunde-Ayinmode, Mosunmola F; Akande, Tanimola M; Ademola-Popoola, Dupe S

    2011-01-01

    Blindness can cause psychosocial distress leading to maladjustment if not mitigated. Maladjustment is a secondary burden that further reduces quality of life of the blind. Adjustment is often personalized and depends on nature and quality of prevailing psychosocial support and rehabilitation opportunities. This study was aimed at identifying the pattern of psychosocial adjustment in a group of relatively secluded and under-reached totally blind people in Ilorin, thus sensitizing eye doctors to psychosocial morbidity and care in the blind. A cross-sectional descriptive study using 20-item Self-Reporting Questionnaire (SRQ) and a pro forma designed by the authors to assess the psychosocial problems and risk factors in some blind people in Ilorin metropolis. The study revealed that most of the blind people were reasonably adjusted in key areas of social interaction, marriage, and family. Majority were considered to be poorly adjusted in the areas of education, vocational training, employment, and mobility. Many were also considered to be psychologically maladjusted based on the high rate of probable psychological disorder of 51%, as determined by SRQ. Factors identified as risk factors of probable psychological disorder were poor educational background and the presence of another medical disorder. Most of the blind had no access to formal education or rehabilitation system, which may have contributed to their maladjustment in the domains identified. Although their prevailing psychosocial situation would have been better prevented yet, real opportunity still exists to help this group of people in the area of social and physical rehabilitation, meeting medical needs, preventive psychiatry, preventive ophthalmology, and community health. This will require the joint efforts of medical community, government and nongovernment organizations to provide the framework for delivery of these services directly to the communities.

  4. Functional Genomic and Proteomic Analysis Reveals Disruption of Myelin-Related Genes and Translation in a Mouse Model of Early Life Neglect

    PubMed Central

    Bordner, Kelly A.; George, Elizabeth D.; Carlyle, Becky C.; Duque, Alvaro; Kitchen, Robert R.; Lam, TuKiet T.; Colangelo, Christopher M.; Stone, Kathryn L.; Abbott, Thomas B.; Mane, Shrikant M.; Nairn, Angus C.; Simen, Arthur A.

    2011-01-01

    Early life neglect is an important public health problem which can lead to lasting psychological dysfunction. Good animal models are necessary to understand the mechanisms responsible for the behavioral and anatomical pathology that results. We recently described a novel model of early life neglect, maternal separation with early weaning (MSEW), that produces behavioral changes in the mouse that persist into adulthood. To begin to understand the mechanism by which MSEW leads to these changes we applied cDNA microarray, next-generation RNA-sequencing (RNA-seq), label-free proteomics, multiple reaction monitoring (MRM) proteomics, and methylation analysis to tissue samples obtained from medial prefrontal cortex to determine the molecular changes induced by MSEW that persist into adulthood. The results show that MSEW leads to dysregulation of markers of mature oligodendrocytes and genes involved in protein translation and other categories, an apparent downward biasing of translation, and methylation changes in the promoter regions of selected dysregulated genes. These findings are likely to prove useful in understanding the mechanism by which early life neglect affects brain structure, cognition, and behavior. PMID:21629843

  5. Early Benefits of a Starter Formula Enriched in Prebiotics and Probiotics on the Gut Microbiota of Healthy Infants Born to HIV+ Mothers: A Randomized Double-Blind Controlled Trial

    PubMed Central

    Cooper, Peter; Bolton, Keith D.; Velaphi, Sithembiso; de Groot, Nanda; Emady-Azar, Shahram; Pecquet, Sophie; Steenhout, Philippe

    2016-01-01

    The gut microbiota of infants is shaped by both the mode of delivery and the type of feeding. The gut of vaginally and cesarean-delivered infants is colonized at different rates and with different bacterial species, leading to differences in the gut microbial composition, which may persist up to 6 months. In a multicenter, randomized, controlled, double-blind trial conducted in South Africa, we tested the effect of a formula supplemented with a prebiotic (a mixture of bovine milk-derived oligosaccharides [BMOS] generated from whey permeate and containing galactooligosaccharides and milk oligosaccharides such as 3′- and 6′-sialyllactose) and the probiotic Bifidobacterium animalis subsp. lactis (B. lactis) strain CNCM I-3446 on the bifidobacteria levels in the gut of infants born vaginally or via cesarean section in early life. Additionally, the safety of the new formulation was evaluated. A total of 430 healthy, full-term infants born to HIV-positive mothers who had elected to feed their child beginning from birth (≤3 days old) exclusively with formula were randomized into this multicenter trial of four parallel groups. A total of 421 infants who had any study formula intake were included in the full analysis set (FAS). The first two groups consisted of cesarean-delivered infants assigned to the Test formula (n = 92) (a starter infant formula [IF] containing BMOS at a total oligosaccharide concentration of 5.8 ± 1.0 g/100 g of powder formula [8 g/L in the reconstituted formula] + B. lactis [1 × 107 colony-forming units {cfu}/g]) or a Control IF (n = 101); the second two groups consisted of vaginally delivered infants randomized to the same Test (n = 115) or Control (n = 113) formulas from the time of enrollment to 6 months. The primary efficacy outcome was fecal bifidobacteria count at 10 days, and the primary safety outcome was daily weight gain (g/d) between 10 days and 4 months. At 10 days, fecal bifidobacteria counts were significantly higher in the Test

  6. Vision rehabilitation in the case of blindness.

    PubMed

    Veraart, Claude; Duret, Florence; Brelén, Marten; Oozeer, Medhy; Delbeke, Jean

    2004-09-01

    This article examines the various vision rehabilitation procedures that are available for early and late blindness. Depending on the pathology involved, several vision rehabilitation procedures exist, or are in development. Visual aids are available for low vision individuals, as are sensory aids for blind persons. Most noninvasive sensory substitution prostheses as well as implanted visual prostheses in development are reviewed. Issues dealing with vision rehabilitation are also discussed, such as problems of biocompatibility, electrical safety, psychosocial aspects, and ethics. Basic studies devoted to vision rehabilitation such as simulation in mathematical models and simulation of artificial vision are also presented. Finally, the importance of accurate rehabilitation assessment is addressed, and tentative market figures are given.

  7. Perception of blindness and blinding eye conditions in rural communities.

    PubMed Central

    Ashaye, Adeyinka; Ajuwon, Ademola Johnson; Adeoti, Caroline

    2006-01-01

    PURPOSE: The purpose of this qualitative study was to explore the causes and management of blindness and blinding eye conditions as perceived by rural dwellers of two Yoruba communities in Oyo State, Nigeria. METHODS: Four focus group discussions were conducted among residents of Iddo and Isale Oyo, two rural Yoruba communities in Oyo State, Nigeria. Participants consisted of sighted, those who were partially or totally blind and community leaders. Ten patent medicine sellers and 12 traditional healers were also interviewed on their perception of the causes and management of blindness in their communities. FINDINGS: Blindness was perceived as an increasing problem among the communities. Multiple factors were perceived to cause blindness, including germs, onchocerciasis and supernatural forces. Traditional healers believed that blindness could be cured, with many claiming that they had previously cured blindness in the past. However, all agreed that patience was an important requirement for the cure of blindness. The patent medicine sellers' reports were similar to those of the traditional healers. The barriers to use of orthodox medicine were mainly fear, misconception and perceived high costs of care. There was a consensus of opinion among group discussants and informants that there are severe social and economic consequences of blindness, including not been able to see and assess the quality of what the sufferer eats, perpetual sadness, loss of sleep and dependence on other persons for daily activities. CONCLUSION: Local beliefs associated with causation, symptoms and management of blindness and blinding eye conditions among rural Yoruba communities identified have provided a bridge for understanding local perspectives and basis for implementing appropriate primary eye care programs. PMID:16775910

  8. Perception of blindness and blinding eye conditions in rural communities.

    PubMed

    Ashaye, Adeyinka; Ajuwon, Ademola Johnson; Adeoti, Caroline

    2006-06-01

    The purpose of this qualitative study was to explore the causes and management of blindness and blinding eye conditions as perceived by rural dwellers of two Yoruba communities in Oyo State, Nigeria. Four focus group discussions were conducted among residents of Iddo and Isale Oyo, two rural Yoruba communities in Oyo State, Nigeria. Participants consisted of sighted, those who were partially or totally blind and community leaders. Ten patent medicine sellers and 12 traditional healers were also interviewed on their perception of the causes and management of blindness in their communities. Blindness was perceived as an increasing problem among the communities. Multiple factors were perceived to cause blindness, including germs, onchocerciasis and supernatural forces. Traditional healers believed that blindness could be cured, with many claiming that they had previously cured blindness in the past. However, all agreed that patience was an important requirement for the cure of blindness. The patent medicine sellers' reports were similar to those of the traditional healers. The barriers to use of orthodox medicine were mainly fear, misconception and perceived high costs of care. There was a consensus of opinion among group discussants and informants that there are severe social and economic consequences of blindness, including not been able to see and assess the quality of what the sufferer eats, perpetual sadness, loss of sleep and dependence on other persons for daily activities. Local beliefs associated with causation, symptoms and management of blindness and blinding eye conditions among rural Yoruba communities identified have provided a bridge for understanding local perspectives and basis for implementing appropriate primary eye care programs.

  9. In vivo loss of function study reveals the short stature homeobox-containing (shox) gene plays indispensable roles in early embryonic growth and bone formation in zebrafish.

    PubMed

    Sawada, Rie; Kamei, Hiroyasu; Hakuno, Fumihiko; Takahashi, Shin-Ichiro; Shimizu, Toshiaki

    2015-02-01

    Congenital loss of the SHOX gene is considered to be a genetic cause of short stature phenotype in Turner syndrome and Leri-Weill dyschondrosteosis patients. Though SHOX expression initiates during early fetal development, little is known about the embryonic roles of SHOX. The evolutionary conservation of the zebrafish shox gene and the convenience of the early developmental stages for analyses make zebrafish a preferred model. Here, we characterized structure, expression, and developmental roles of zebrafish shox through a loss-of-function approach. We found a previously undiscovered Shox protein that has both a homeodomain and an OAR-domain in zebrafish. The shox transcript emerged during the segmentation period and it increased in later stages. The predominant domains of shox expression were mandibular arch, pectoral fin, anterior notochord, rhombencephalon, and mesencephalon, suggesting that Shox is involved in bone and neural development. Translational blockade of Shox mRNA by an antisense morpholino oligo delayed embryonic growth, which was restored by the co-overexpression of morpholino-resistant Shox mRNA. At later stages, impaired Shox expression markedly delayed the calcification process in the anterior vertebral column and craniofacial bones. Our data demonstrate evolutionarily conserved Shox plays roles in early embryonic growth and in later bone formation. © 2014 Wiley Periodicals, Inc.

  10. Fighting blindness with microelectronics.

    PubMed

    Zrenner, Eberhart

    2013-11-06

    There is no approved cure for blindness caused by degeneration of the photoreceptor cells of the retina. However, there has been encouraging progress with attempts to restore vision using microelectronic retinal implant devices. Yet many questions remain to be addressed. Where is the best location to implant multielectrode arrays? How can spatial and temporal resolution be improved? What are the best ways to ensure the safety and longevity of these devices? Will color vision be possible? This Perspective discusses the current state of the art of retinal implants and attempts to address some of the outstanding questions.

  11. Late onset seizures, hemiparesis and blindness in hemolytic uremic syndrome.

    PubMed

    Bennett, B; Booth, T; Quan, A

    2003-03-01

    Neurologic complications of hemolytic uremic syndrome, including seizures, usually occur early during the acute phase of the illness. We report a3-year-old girl with classic diarrhea-associated hemolytic uremic syndrome who developed late onset seizures, hemiparesis and transient blindness on the 17th hospital day, at which time her recovery was characterized by improvement in her blood pressure, serum electrolytes, renal function, hematocrit and platelet count. A CT and MR revealed brainstem and posterior parietal and occipital infarct/edema. The association of these radiologic findings within the posterior distribution along with visual loss and seizures are unique to posterior reversible encephalopathy syndrome. Within 7 days, she regained motor function and vision and had no further seizure activity. At 6 months follow-up, physical examination revealed normal motor function and vision and a repeat MR showed near resolution of the previous findings with minimal occipital lobe gliosis. This case report describes the uncommon finding of late onset seizures occurring during the recovery phase of hemolytic uremic syndrome with MR findings consistent with posterior reversible encephalopathy syndrome.

  12. Memory for environmental sounds in sighted, congenitally blind and late blind adults: evidence for cross-modal compensation.

    PubMed

    Röder, Brigitte; Rösler, Frank

    2003-10-01

    Several recent reports suggest compensatory performance changes in blind individuals. It has, however, been argued that the lack of visual input leads to impoverished semantic networks resulting in the use of data-driven rather than conceptual encoding strategies on memory tasks. To test this hypothesis, congenitally blind and sighted participants encoded environmental sounds either physically or semantically. In the recognition phase, both conceptually as well as physically distinct and physically distinct but conceptually highly related lures were intermixed with the environmental sounds encountered during study. Participants indicated whether or not they had heard a sound in the study phase. Congenitally blind adults showed elevated memory both after physical and semantic encoding. After physical encoding blind participants had lower false memory rates than sighted participants, whereas the false memory rates of sighted and blind participants did not differ after semantic encoding. In order to address the question if compensatory changes in memory skills are restricted to critical periods during early childhood, late blind adults were tested with the same paradigm. When matched for age, they showed similarly high memory scores as the congenitally blind. These results demonstrate compensatory performance changes in long-term memory functions due to the loss of a sensory system and provide evidence for high adaptive capabilities of the human cognitive system.

  13. Motion-Dependent Filling-In of Spatiotemporal Information at the Blind Spot

    PubMed Central

    Maus, Gerrit W.; Whitney, David

    2016-01-01

    We usually do not notice the blind spot, a receptor-free region on the retina. Stimuli extending through the blind spot appear filled in. However, if an object does not reach through but ends in the blind spot, it is perceived as “cut off” at the boundary. Here we show that even when there is no corresponding stimulation at opposing edges of the blind spot, well known motion-induced position shifts also extend into the blind spot and elicit a dynamic filling-in process that allows spatial structure to be extrapolated into the blind spot. We presented observers with sinusoidal gratings that drifted into or out of the blind spot, or flickered in counterphase. Gratings moving into the blind spot were perceived to be longer than those moving out of the blind spot or flickering, revealing motion-dependent filling-in. Further, observers could perceive more of a grating’s spatial structure inside the blind spot than would be predicted from simple filling-in of luminance information from the blind spot edge. This is evidence for a dynamic filling-in process that uses spatiotemporal information from the motion system to extrapolate visual percepts into the scotoma of the blind spot. Our findings also provide further support for the notion that an explicit spatial shift of topographic representations contributes to motion-induced position illusions. PMID:27100795

  14. Motion-Dependent Filling-In of Spatiotemporal Information at the Blind Spot.

    PubMed

    Maus, Gerrit W; Whitney, David

    2016-01-01

    We usually do not notice the blind spot, a receptor-free region on the retina. Stimuli extending through the blind spot appear filled in. However, if an object does not reach through but ends in the blind spot, it is perceived as "cut off" at the boundary. Here we show that even when there is no corresponding stimulation at opposing edges of the blind spot, well known motion-induced position shifts also extend into the blind spot and elicit a dynamic filling-in process that allows spatial structure to be extrapolated into the blind spot. We presented observers with sinusoidal gratings that drifted into or out of the blind spot, or flickered in counterphase. Gratings moving into the blind spot were perceived to be longer than those moving out of the blind spot or flickering, revealing motion-dependent filling-in. Further, observers could perceive more of a grating's spatial structure inside the blind spot than would be predicted from simple filling-in of luminance information from the blind spot edge. This is evidence for a dynamic filling-in process that uses spatiotemporal information from the motion system to extrapolate visual percepts into the scotoma of the blind spot. Our findings also provide further support for the notion that an explicit spatial shift of topographic representations contributes to motion-induced position illusions.

  15. Early Pan-African evolution of the basement around Elat, Israel, and the Sinai Peninsula revealed by single-zircon evaporation dating, and implications for crustal accretion rates

    SciTech Connect

    Kroener, A.; Eyal, M.; Eyal, Y.

    1990-06-01

    The authors report {sup 207}Pb/{sup 206}Pb single-zircon evaporation ages for early Pan-African rocks from southern Israel and the northeastern Sinai Peninsula, the northernmost extension of the Arabian-Nubian shield. The oldest rocks are metamorphic schists of presumed island-arc derivation; detrital zircons date the source terrain at ca. 800-820 Ma. A major phase of tonalite-trondhjemite plutonism occurred at ca. 760-780 Ma; more evolved granitic rocks were emplaced at about 745 Ma. A metagabbro-metadiorite complex reflects the youngest igneous phase at ca. 640 Ma. We find no evidence for pre-Pan-African crust, and our data document important crust-forming events that correlate with similar episodesmore » elsewhere in the shield. The widespread presence of early Pan-African juvenile rocks (i.e., ca. 760-850 Ma) in many parts of the Arabian-Nubian shield makes this period the most important in the magmatic history of the shield and supports earlier suggestions for unusually high crust-production rates.« less

  16. Ultra-deep sequencing of ribosome-associated poly-adenylated RNA in early Drosophila embryos reveals hundreds of conserved translated sORFs.

    PubMed

    Li, Hongmei; Hu, Chuansheng; Bai, Ling; Li, Hua; Li, Mingfa; Zhao, Xiaodong; Czajkowsky, Daniel M; Shao, Zhifeng

    2016-12-01

    There is growing recognition that small open reading frames (sORFs) encoding peptides shorter than 100 amino acids are an important class of functional elements in the eukaryotic genome, with several already identified to play critical roles in growth, development, and disease. However, our understanding of their biological importance has been hindered owing to the significant technical challenges limiting their annotation. Here we combined ultra-deep sequencing of ribosome-associated poly-adenylated RNAs with rigorous conservation analysis to identify a comprehensive population of translated sORFs during early Drosophila embryogenesis. In total, we identify 399 sORFs, including those previously annotated but without evidence of translational capacity, those found within transcripts previously classified as non-coding, and those not previously known to be transcribed. Further, we find, for the first time, evidence for translation of many sORFs with different isoforms, suggesting their regulation is as complex as longer ORFs. Furthermore, many sORFs are found not associated with ribosomes in late-stage Drosophila S2 cells, suggesting that many of the translated sORFs may have stage-specific functions during embryogenesis. These results thus provide the first comprehensive annotation of the sORFs present during early Drosophila embryogenesis, a necessary basis for a detailed delineation of their function in embryogenesis and other biological processes. © The Author 2016. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  17. Diffusion tractography and graph theory analysis reveal the disrupted rich-club organization of white matter structural networks in early Tourette Syndrome children

    NASA Astrophysics Data System (ADS)

    Wen, Hongwei; Liu, Yue; Wang, Shengpei; Zhang, Jishui; Peng, Yun; He, Huiguang

    2017-03-01

    Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder. At present, the topological disruptions of the whole brain white matter (WM) structural networks remain poorly understood in TS children. Considering the unique position of the topologically central role of densely interconnected brain hubs, namely the rich club regions, therefore, we aimed to investigate whether the rich club regions and their related connections would be particularly vulnerable in early TS children. In our study, we used diffusion tractography and graph theoretical analyses to explore the rich club structures in 44 TS children and 48 healthy children. The structural networks of TS children exhibited significantly increased normalized rich club coefficient, suggesting that TS is characterized by increased structural integrity of this centrally embedded rich club backbone, potentially resulting in increased global communication capacity. In addition, TS children showed a reorganization of rich club regions, as well as significantly increased density and decreased number in feeder connections. Furthermore, the increased rich club coefficients and feeder connections density of TS children were significantly positively correlated to tic severity, indicating that TS may be characterized by a selective alteration of the structural connectivity of the rich club regions, tending to have higher bridging with non-rich club regions, which may increase the integration among tic-related brain circuits with more excitability but less inhibition for information exchanges between highly centered brain regions and peripheral areas. In all, our results suggest the disrupted rich club organization in early TS children and provide structural insights into the brain networks.

  18. The massacre mass grave of Schöneck-Kilianstädten reveals new insights into collective violence in Early Neolithic Central Europe

    PubMed Central

    Meyer, Christian; Lohr, Christian; Gronenborn, Detlef; Alt, Kurt W.

    2015-01-01

    Conflict and warfare are central but also disputed themes in discussions about the European Neolithic. Although a few recent population studies provide broad overviews, only a very limited number of currently known key sites provide precise insights into moments of extreme and mass violence and their impact on Neolithic societies. The massacre sites of Talheim, Germany, and Asparn/Schletz, Austria, have long been the focal points around which hypotheses concerning a final lethal crisis of the first Central European farmers of the Early Neolithic Linearbandkeramik Culture (LBK) have concentrated. With the recently examined LBK mass grave site of Schöneck-Kilianstädten, Germany, we present new conclusive and indisputable evidence for another massacre, adding new data to the discussion of LBK violence patterns. At least 26 individuals were violently killed by blunt force and arrow injuries before being deposited in a commingled mass grave. Although the absence and possible abduction of younger females has been suggested for other sites previously, a new violence-related pattern was identified here: the intentional and systematic breaking of lower limbs. The abundance of the identified perimortem fractures clearly indicates torture and/or mutilation of the victims. The new evidence presented here for unequivocal lethal violence on a large scale is put into perspective for the Early Neolithic of Central Europe and, in conjunction with previous results, indicates that massacres of entire communities were not isolated occurrences but rather were frequent features of the last phases of the LBK. PMID:26283359

  19. Zif268 mRNA Expression Patterns Reveal a Distinct Impact of Early Pattern Vision Deprivation on the Development of Primary Visual Cortical Areas in the Cat.

    PubMed

    Laskowska-Macios, Karolina; Zapasnik, Monika; Hu, Tjing-Tjing; Kossut, Malgorzata; Arckens, Lutgarde; Burnat, Kalina

    2015-10-01

    Pattern vision deprivation (BD) can induce permanent deficits in global motion perception. The impact of timing and duration of BD on the maturation of the central and peripheral visual field representations in cat primary visual areas 17 and 18 remains unknown. We compared early BD, from eye opening for 2, 4, or 6 months, with late onset BD, after 2 months of normal vision, using the expression pattern of the visually driven activity reporter gene zif268 as readout. Decreasing zif268 mRNA levels between months 2 and 4 characterized the normal maturation of the (supra)granular layers of the central and peripheral visual field representations in areas 17 and 18. In general, all BD conditions had higher than normal zif268 levels. In area 17, early BD induced a delayed decrease, beginning later in peripheral than in central area 17. In contrast, the decrease occurred between months 2 and 4 throughout area 18. Lack of pattern vision stimulation during the first 4 months of life therefore has a different impact on the development of areas 17 and 18. A high zif268 expression level at a time when normal vision is restored seems to predict the capacity of a visual area to compensate for BD. © The Author 2014. Published by Oxford University Press.

  20. Using the Workforce Investment Act of 1998 to Benefit Youth with Blindness and Visual Impairment

    ERIC Educational Resources Information Center

    Mitchell, Patrick J.; Zampitella-Freese, Christina

    2003-01-01

    Overbrook School for the Blind (OSB), a specialized school serving students with blindness and visual impairment, has provided, since the early 1990s, paid summer work experiences as part of the school's Work Experience Program. In this article, the authors discuss how OSB has strengthened its original program as a result of the Workforce…

  1. Corneal blindness: a global perspective.

    PubMed Central

    Whitcher, J. P.; Srinivasan, M.; Upadhyay, M. P.

    2001-01-01

    Diseases affecting the cornea are a major cause of blindness worldwide, second only to cataract in overall importance. The epidemiology of corneal blindness is complicated and encompasses a wide variety of infectious and inflammatory eye diseses that cause corneal scarring, which ultimately leads to functional blindness. In addition, the prevalence of corneal disease varies from country to country and even from one population to another. While cataract is responsible for nearly 20 million of the 45 million blind people in the world, the next major cause is trachoma which blinds 4.9 million individuals, mainly as a result of corneal scarring and vascularization. Ocular trauma and corneal ulceration are significant causes of corneal blindness that are often underreported but may be responsible for 1.5-2.0 million new cases of monocular blindness every year. Causes of childhood blindness (about 1.5 million worldwide with 5 million visually disabled) include xerophthalmia (350,000 cases annually), ophthalmia neonatorum, and less frequently seen ocular diseases such as herpes simplex virus infections and vernal keratoconjunctivitis. Even though the control of onchocerciasis and leprosy are public health success stories, these diseases are still significant causes of blindness--affecting a quarter of a million individuals each. Traditional eye medicines have also been implicated as a major risk factor in the current epidemic of corneal ulceration in developing countries. Because of the difficulty of treating corneal blindness once it has occurred, public health prevention programmes are the most cost-effective means of decreasing the global burden of corneal blindness. PMID:11285665

  2. Blinded by Zika? A missed HIV diagnosis that resulted in optic neuropathy and blindness: a case report.

    PubMed

    Hirschel, Tiffany; Steffen, Heimo; Pecoul, Victor; Calmy, Alexandra

    2017-12-01

    Typical symptoms of an acute human immunodeficiency virus (HIV) infections like fever and rash are not specific and can be caused by a multitude of other pathogens, such as Zika or rickettsiosis. Up to 30% of primary HIV infection do not present with the typical flu-like symptoms and thus represent a diagnostic challenge. In this report, we describe a rare case of optic neuropathy as the initial presentation of primary HIV infection, which resulted in irreversible blindness. To our knowledge, only four cases of optic neuropathy resulting from a recent HIV seroconversion have been reported. In January 2015, a 72-year-old man presented with a rash, fever and diffuse myalgias after returning from a fortnight in Cuba. In the context of the current polemic, Zika was considered likely. A diagnostic work-up, including dengue fever and Zika, was negative. Symptoms resolved spontaneously. In March, the patient experienced a sudden loss of vision first on one, a few days later on the other eye. Magnetic resonance imaging showed optic nerve enhancement suggesting neuritis. Numerous infective causes were sought and the patient was diagnosed with HIV. Corticosteroids and antiretroviral therapy were initiated but vision did not improve. Four weeks later an optic atrophy developed. After more than a year of follow-up the patient remains blind. Stored serum from January revealed a detectable viremia with a negative Western blot assay, typical of acute HIV infection. Optic neuritis is a rare complication of early HIV infection. Only four others cases have been described, some of which recovered their vision after the administration of corticosteroids and/or ARV treatment. The balance between ischemic and neuroimmune processes may play a role in recovery. Delayed diagnosis, due to an unjustified focus on the Zika virus may have contributed to the tragic outcome.

  3. Convergence of topological domain boundaries, insulators, and polytene interbands revealed by high-resolution mapping of chromatin contacts