WorldWideScience

Sample records for human neuropathology similarities

  1. Neuropathology

    International Nuclear Information System (INIS)

    Kaufman, M.A.; Roizin, L.; Gold, G.

    1971-01-01

    The etiology of neuropathies in man and animals is reviewed. X-irradiation of rabbits on the 18th day of fetal life with 150 r disturbed the normal developmental changes of tissue respiration and anaerobic glycolysis of brain during ontogenesis. X-irradiation of the brain of 7-day-old rats (600 r) resulted in a large selective deficit of cerebellar weight at 7 1 / 2 months with a substantial increase of cellularity. A reduction in the cellular response to superficial freezing injury was dependent on the dosage of previous local brain x-irradiation, but independent of the time interval between irradiation and injury. It was suggested that radiation damage was stored up in local cells until they were stimulated to divide, when they died. Similar modifications were also induced in the response to subsequent intracerebral infection with Bacillus pertussis and were believed to support the view that brain macrophages are of local origin. The similarity of mast cell changes induced by compound 48/80 in both acute and chronic stages to those in irradiated monkey brains suggested that some of the lesions may reflect a process of delayed hypersensitivity with antigen provided by some component of the mast cells. (U.S.)

  2. Changing patterns of human immunodeficiency virus-associated neuropathology

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    Gray Francoise

    2007-01-01

    Full Text Available This paper describes the evolution of the pathogenic concepts associated with the infection by the human immunodeficiency virus (HIV, with emphasis to the pathology of the nervous system. Although the first description of damage to the nervous system in the acquired immunodeficiency syndrome (AIDS only appeared in 1982, the dramatic diffusion of the epidemic worldwide, as well as the invariably rapidly fatal outcome of the disease before the introduction of efficient treatment, generated from the beginning an enormous amount of research and re-thinking on a number of pathogenetic concepts. Less than 25 years after the first autopsy series on AIDS patients were published and the virus responsible for AIDS was identified, satisfactory definition and classification of a number of neuropathological complications of HIV infection have been established. This has led to the establishment of accurate clinical and biological diagnosis of the main neurological complications of the disease, which remain a major cause of disability and death in patients. Clinical and experimental studies have provided essential insight into the pathogenesis of CNS lesions and the natural history of the disorder. The relatively recent introduction of effective antiretroviral therapy in 1995-6 dramatically improved the course of prognosis of HIV disease. However, there remain a number of unsolved pathogenetic issues, the most puzzling of which remains the precise mechanism of neuronal damage underlying the specific HIV-related cognitive disorder (HIV-dementia. In addition, although antiretroviral therapy has changed the course of neurological complications, new issues have emerged, such as the lack of improvement or even paradoxical deterioration of the neurological status in treated patients. Interpretation of these complications remains largely speculative, partly because of the small number of neuropathological studies related to the beneficial consequence of this

  3. Alzheimer’s disease is not “brain aging”: neuropathological, genetic, and epidemiological human studies

    Science.gov (United States)

    Head, Elizabeth; Schmitt, Frederick A.; Davis, Paulina R.; Neltner, Janna H.; Jicha, Gregory A.; Abner, Erin L.; Smith, Charles D.; Van Eldik, Linda J.; Kryscio, Richard J.; Scheff, Stephen W.

    2011-01-01

    Human studies are reviewed concerning whether “aging”-related mechanisms contribute to Alzheimer’s disease (AD) pathogenesis. AD is defined by specific neuropathology: neuritic amyloid plaques and neocortical neurofibrillary tangles. AD pathology is driven by genetic factors related not to aging per se, but instead to the amyloid precursor protein (APP). In contrast to genes involved in APP-related mechanisms, there is no firm connection between genes implicated in human “accelerated aging” diseases (progerias) and AD. The epidemiology of AD in advanced age is highly relevant but deceptively challenging to address given the low autopsy rates in most countries. In extreme old age, brain diseases other than AD approximate AD prevalence while the impact of AD pathology appears to peak by age 95 and decline thereafter. Many distinct brain diseases other than AD afflict older human brains and contribute to cognitive impairment. Additional prevalent pathologies include cerebrovascular disease and hippocampal sclerosis, both high-morbidity brain diseases that appear to peak in incidence later than AD chronologically. Because of these common brain diseases of extreme old age, the epidemiology differs between clinical “dementia” and the subset of dementia cases with AD pathology. Additional aging-associated mechanisms for cognitive decline such as diabetes and synapse loss have been linked to AD and these hypotheses are discussed. Criteria are proposed to define an “aging-linked” disease, and AD fails all of these criteria. In conclusion, it may be most fruitful to focus attention on specific pathways involved in AD rather than attributing it to an inevitable consequence of aging. PMID:21516511

  4. Similarity increases altruistic punishment in humans.

    Science.gov (United States)

    Mussweiler, Thomas; Ockenfels, Axel

    2013-11-26

    Humans are attracted to similar others. As a consequence, social networks are homogeneous in sociodemographic, intrapersonal, and other characteristics--a principle called homophily. Despite abundant evidence showing the importance of interpersonal similarity and homophily for human relationships, their behavioral correlates and cognitive foundations are poorly understood. Here, we show that perceived similarity substantially increases altruistic punishment, a key mechanism underlying human cooperation. We induced (dis)similarity perception by manipulating basic cognitive mechanisms in an economic cooperation game that included a punishment phase. We found that similarity-focused participants were more willing to punish others' uncooperative behavior. This influence of similarity is not explained by group identity, which has the opposite effect on altruistic punishment. Our findings demonstrate that pure similarity promotes reciprocity in ways known to encourage cooperation. At the same time, the increased willingness to punish norm violations among similarity-focused participants provides a rationale for why similar people are more likely to build stable social relationships. Finally, our findings show that altruistic punishment is differentially involved in encouraging cooperation under pure similarity vs. in-group conditions.

  5. Humans and mice express similar olfactory preferences.

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    Nathalie Mandairon

    Full Text Available In humans, the pleasantness of odors is a major contributor to social relationships and food intake. Smells evoke attraction and repulsion responses, reflecting the hedonic value of the odorant. While olfactory preferences are known to be strongly modulated by experience and learning, it has been recently suggested that, in humans, the pleasantness of odors may be partly explained by the physicochemical properties of the odorant molecules themselves. If odor hedonic value is indeed predetermined by odorant structure, then it could be hypothesized that other species will show similar odor preferences to humans. Combining behavioral and psychophysical approaches, we here show that odorants rated as pleasant by humans were also those which, behaviorally, mice investigated longer and human subjects sniffed longer, thereby revealing for the first time a component of olfactory hedonic perception conserved across species. Consistent with this, we further show that odor pleasantness rating in humans and investigation time in mice were both correlated with the physicochemical properties of the molecules, suggesting that olfactory preferences are indeed partly engraved in the physicochemical structure of the odorant. That odor preferences are shared between mammal species and are guided by physicochemical features of odorant stimuli strengthens the view that odor preference is partially predetermined. These findings open up new perspectives for the study of the neural mechanisms of hedonic perception.

  6. Spontaneous ischaemic stroke lesions in a dog brain: neuropathological characterisation and comparison to human ischaemic stroke

    DEFF Research Database (Denmark)

    Thomsen, Barbara Blicher; Gredal, Hanne; Wirenfeldt, Martin

    2017-01-01

    Background Dogs develop spontaneous ischaemic stroke with a clinical picture closely resembling human ischaemic stroke patients. Animal stroke models have been developed, but it has proved difficult to translate results obtained from such models into successful therapeutic strategies in human str...

  7. Digital stereology in neuropathology

    DEFF Research Database (Denmark)

    Kristiansen, Sarah Line Brøgger; Nyengaard, Jens Randel

    2012-01-01

    will therefore present the relevant stereological estimators for obtaining reliable quantitative structural data from brains and peripheral nerves when using digital light microscopy. It is discussed how to obtain brain and nerve fibre samples to fulfil the requirements for the estimators. A presentation......-dimensional structural knowledge. Accordingly, stereology is a science based on statistical sampling principles and geometric measures. The application of stereology to neuropathological studies allows the researcher to efficiently obtain a precise estimate of various structural quantities. This neuropathological review...

  8. Manganese Neurotoxicity: New Perspectives from Behavioral, Neuroimaging, and Neuropathological Studies in Humans and Non-Human Primates

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    Tomas R Guilarte

    2013-06-01

    Full Text Available Manganese (Mn is an essential metal and has important physiological functions for human health. However, exposure to excess levels of Mn in occupational settings or from environmental sources has been associated with a neurological syndrome comprising cognitive deficits, neuropsychological abnormalities and parkinsonism. Historically, studies on the effects of Mn in humans and experimental animals have been concerned with effects on the basal ganglia and the dopaminergic system as it relates to movement abnormalities. However, emerging studies are beginning to provide significant evidence of Mn effects on cortical structures and cognitive function at lower levels than previously recognized. This review advances new knowledge of putative mechanisms by which exposure to excess levels of Mn alters neurobiological systems and produces neurological deficits not only in the basal ganglia but also in the cerebral cortex. The emerging evidence suggests that working memory is significantly affected by chronic Mn exposure and this may be mediated by alterations in brain structures associated with the working memory network including the caudate nucleus in the striatum, frontal cortex and parietal cortex. Dysregulation of the dopaminergic system may play an important role in both the movement abnormalities as well as the neuropsychiatric and cognitive function deficits that have been described in humans and non-human primates exposed to Mn.

  9. Neuropathological diagnostic accuracy.

    NARCIS (Netherlands)

    Murphy, M.; Loosemore, A.; Ferrer, I.; Wesseling, P.; Wilkins, P.R.; Bell, B.A.

    2002-01-01

    This study investigated variations in neuropathological diagnosis when histopathological slides are evaluated with access to all information pertinent to a case, compared with evaluation of H & E stained slides with only limited clinical information. The aim of the study is to evaluate the role of

  10. A Similarity Analysis of Audio Signal to Develop a Human Activity Recognition Using Similarity Networks

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    Alejandra García-Hernández

    2017-11-01

    Full Text Available Human Activity Recognition (HAR is one of the main subjects of study in the areas of computer vision and machine learning due to the great benefits that can be achieved. Examples of the study areas are: health prevention, security and surveillance, automotive research, and many others. The proposed approaches are carried out using machine learning techniques and present good results. However, it is difficult to observe how the descriptors of human activities are grouped. In order to obtain a better understanding of the the behavior of descriptors, it is important to improve the abilities to recognize the human activities. This paper proposes a novel approach for the HAR based on acoustic data and similarity networks. In this approach, we were able to characterize the sound of the activities and identify those activities looking for similarity in the sound pattern. We evaluated the similarity of the sounds considering mainly two features: the sound location and the materials that were used. As a result, the materials are a good reference classifying the human activities compared with the location.

  11. [-25]A Similarity Analysis of Audio Signal to Develop a Human Activity Recognition Using Similarity Networks.

    Science.gov (United States)

    García-Hernández, Alejandra; Galván-Tejada, Carlos E; Galván-Tejada, Jorge I; Celaya-Padilla, José M; Gamboa-Rosales, Hamurabi; Velasco-Elizondo, Perla; Cárdenas-Vargas, Rogelio

    2017-11-21

    Human Activity Recognition (HAR) is one of the main subjects of study in the areas of computer vision and machine learning due to the great benefits that can be achieved. Examples of the study areas are: health prevention, security and surveillance, automotive research, and many others. The proposed approaches are carried out using machine learning techniques and present good results. However, it is difficult to observe how the descriptors of human activities are grouped. In order to obtain a better understanding of the the behavior of descriptors, it is important to improve the abilities to recognize the human activities. This paper proposes a novel approach for the HAR based on acoustic data and similarity networks. In this approach, we were able to characterize the sound of the activities and identify those activities looking for similarity in the sound pattern. We evaluated the similarity of the sounds considering mainly two features: the sound location and the materials that were used. As a result, the materials are a good reference classifying the human activities compared with the location.

  12. Similarity or dissimilarity in the relations between human service organizations.

    Science.gov (United States)

    Bruynooghe, Kevin; Verhaeghe, Mieke; Bracke, Piet

    2008-01-01

    Exchange theory and homophily theory give rise to counteracting expectations for the interaction between human service organizations. Based on arguments of exchange theory, more interaction is expected between dissimilar organizations having complementary resources. Based on arguments of homophily theory, organizations having similar characteristics are expected to interact more. Interorganizational relations between human service organizations in two regional networks in Flanders are examined in this study. Results indicate that human service organizations tend to cooperate more with similar organizations as several homophily effects but not one effect of dissimilarity were found to be significant. The results of this study contribute to the understanding of interorganizational networks of human service organizations and have implications for the development of integrated care.

  13. Similar Fracture Patterns in Human Nose and Gothic Cathedral.

    Science.gov (United States)

    Lee, Shu Jin; Tse, Kwong Ming; Lee, Heow Pueh

    2015-10-01

    This study proposes that the bony anatomy of the human nose and masonry structure of the Gothic cathedral are geometrically similar, and have common fracture patterns. We also aim to correlate the fracture patterns observed in patients' midface structures with those seen in the Gothic cathedral using computational approach. CT scans of 33 patients with facial fractures were examined and compared with computer simulations of both the Gothic cathedral and human nose. Three similar patterns were found: (1) Cracks of the nasal arch with crumpling of the vertical buttresses akin to the damage seen during minor earthquakes; (2) lateral deviation of the central nasal arch and collapse of the vertical buttresses akin to those due to lateral forces from wind and in major earthquakes; and (3) Central arch collapse seen as a result of collapse under excessive dead weight. Interestingly, the finding of occult nasal and septal fractures in the mandible fractures with absence of direct nasal trauma highlights the possibility of transmission of forces from the foundation to the arch leading to structural failure. It was also found that the structural buttresses of the Gothic cathedral delineate the vertical buttresses in the human midface structure. These morphologic similarities between the human nose and Gothic cathedral will serve as a basis to study the biomechanics of nasal fractures. Identification of structural buttresses in a skeletal structure has important implications for reconstruction as reestablishment of structural continuity restores normal anatomy and architectural stability of the human midface structure. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  14. The neuropathology of sport.

    Science.gov (United States)

    McKee, Ann C; Daneshvar, Daniel H; Alvarez, Victor E; Stein, Thor D

    2014-01-01

    The benefits of regular exercise, physical fitness and sports participation on cardiovascular and brain health are undeniable. Physical activity reduces the risk for cardiovascular disease, type 2 diabetes, hypertension, obesity, and stroke, and produces beneficial effects on cholesterol levels, antioxidant systems, inflammation, and vascular function. Exercise also enhances psychological health, reduces age-related loss of brain volume, improves cognition, reduces the risk of developing dementia, and impedes neurodegeneration. Nonetheless, the play of sports is associated with risks, including a risk for mild TBI (mTBI) and, rarely, catastrophic traumatic injury and death. There is also growing awareness that repetitive mTBIs, such as concussion and subconcussion, can occasionally produce persistent cognitive, behavioral, and psychiatric problems as well as lead to the development of a neurodegeneration, chronic traumatic encephalopathy (CTE). In this review, we summarize the beneficial aspects of sports participation on psychological, emotional, physical and cognitive health, and specifically analyze some of the less common adverse neuropathological outcomes, including concussion, second-impact syndrome, juvenile head trauma syndrome, catastrophic sudden death, and CTE. CTE is a latent neurodegeneration clinically associated with behavioral changes, executive dysfunction and cognitive impairments, and pathologically characterized by frontal and temporal lobe atrophy, neuronal and axonal loss, and abnormal deposits of paired helical filament (PHF)-tau and 43 kDa TAR deoxyribonucleic acid (DNA)-binding protein (TDP-43). CTE often occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including motor neuron disease (CTE-MND). Although the incidence and prevalence of CTE are not known, CTE has been reported most frequently in American football players and boxers. Other sports associated with CTE include ice hockey, professional

  15. Phytomonas serpens: immunological similarities with the human trypanosomatid pathogens.

    Science.gov (United States)

    Santos, André L S; d'Avila-Levy, Claudia M; Elias, Camila G R; Vermelho, Alane B; Branquinha, Marta H

    2007-07-01

    The present review provides an overview of recent discoveries concerning the immunological similarities between Phytomonas serpens, a tomato parasite, and human trypanosomatid pathogens, with special emphasis on peptidases. Leishmania spp. and Trypanosoma cruzi express peptidases that are well-known virulence factors, named leishmanolysin and cruzipain. P. serpens synthesizes two distinct classes of proteolytic enzymes, metallo- and cysteine-type peptidases, that share common epitopes with leishmanolysin and cruzipain, respectively. The leishmanolysin-like and cruzipain-like molecules from P. serpens participate in several biological processes including cellular growth and adhesion to the salivary glands of Oncopeltus fasciatus, a phytophagous insect experimental model. Since previous reports demonstrated that immunization of mice with P. serpens induced a partial protective immune response against T. cruzi, this plant trypanosomatid may be a suitable candidate for vaccine studies. Moreover, comparative approaches in the Trypanosomatidae family may be useful to understand kinetoplastid biology, biochemistry and evolution.

  16. Neuropathology in mice expressing mouse alpha-synuclein.

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    Claus Rieker

    Full Text Available α-Synuclein (αSN in human is tightly linked both neuropathologically and genetically to Parkinson's disease (PD and related disorders. Disease-causing properties in vivo of the wildtype mouse ortholog (mαSN, which carries a threonine at position 53 like the A53T human mutant version that is genetically linked to PD, were never reported. To this end we generated mouse lines that express mαSN in central neurons at levels reaching up to six-fold compared to endogenous mαSN. Unlike transgenic mice expressing human wildtype or mutant forms of αSN, these mαSN transgenic mice showed pronounced ubiquitin immunopathology in spinal cord and brainstem. Isoelectric separation of mαSN species revealed multiple isoforms including two Ser129-phosphorylated species in the most severely affected brain regions. Neuronal Ser129-phosphorylated αSN occurred in granular and small fibrillar aggregates and pathological staining patterns in neurites occasionally revealed a striking ladder of small alternating segments staining either for Ser129-phosphorylated αSN or ubiquitin but not both. Axonal degeneration in long white matter tracts of the spinal cord, with breakdown of myelin sheaths and degeneration of neuromuscular junctions with loss of integrity of the presynaptic neurofilament network in mαSN transgenic mice, was similar to what we have reported for mice expressing human αSN wildtype or mutant forms. In hippocampal neurons, the mαSN protein accumulated and was phosphorylated but these neurons showed no ubiquitin immunopathology. In contrast to the early-onset motor abnormalities and muscle weakness observed in mice expressing human αSN, mαSN transgenic mice displayed only end-stage phenotypic alterations that manifested alongside with neuropathology. Altogether these findings show that increased levels of wildtype mαSN does not induce early-onset behavior changes, but drives end-stage pathophysiological changes in murine neurons that are

  17. Neuropathological Alterations in Alzheimer Disease

    Science.gov (United States)

    Serrano-Pozo, Alberto; Frosch, Matthew P.; Masliah, Eliezer; Hyman, Bradley T.

    2011-01-01

    The neuropathological hallmarks of Alzheimer disease (AD) include “positive” lesions such as amyloid plaques and cerebral amyloid angiopathy, neurofibrillary tangles, and glial responses, and “negative” lesions such as neuronal and synaptic loss. Despite their inherently cross-sectional nature, postmortem studies have enabled the staging of the progression of both amyloid and tangle pathologies, and, consequently, the development of diagnostic criteria that are now used worldwide. In addition, clinicopathological correlation studies have been crucial to generate hypotheses about the pathophysiology of the disease, by establishing that there is a continuum between “normal” aging and AD dementia, and that the amyloid plaque build-up occurs primarily before the onset of cognitive deficits, while neurofibrillary tangles, neuron loss, and particularly synaptic loss, parallel the progression of cognitive decline. Importantly, these cross-sectional neuropathological data have been largely validated by longitudinal in vivo studies using modern imaging biomarkers such as amyloid PET and volumetric MRI. PMID:22229116

  18. Ontogenetic trajectories of chimpanzee social play: similarities with humans.

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    Giada Cordoni

    Full Text Available Social play, a widespread phenomenon in mammals, is a multifunctional behavior, which can have many different roles according to species, sex, age, relationship quality between playmates, group membership, context, and habitat. Play joins and cuts across a variety of disciplines leading directly to inquiries relating to individual developmental changes and species adaptation, thus the importance of comparative studies appears evident. Here, we aim at proposing a possible ontogenetic pathway of chimpanzee play (Pan troglodytes and contrast our data with those of human play. Chimpanzee play shows a number of changes from infancy to juvenility. Particularly, solitary and social play follows different developmental trajectories. While solitary play peaks in infancy, social play does not show any quantitative variation between infancy and juvenility but shows a strong qualitative variation in complexity, asymmetry, and playmate choice. Like laughter in humans, the playful expressions in chimpanzees (at the different age phases seem to have a role in advertising cooperative dispositions and intentions thus increasing the likelihood of engaging in solid social relationships. In conclusion, in chimpanzees, as in humans, both play behavior and the signals that accompany play serve multiple functions according to the different age phases.

  19. Neuropathological Changes and Clinical Features of Autism Spectrum Disorder Participants Are Similar to that Reported in Congenital and Chronic Cerebral Toxoplasmosis in Humans and Mice

    Science.gov (United States)

    Prandota, Joseph

    2010-01-01

    Anatomic, histopathologic, and MRI/SPET studies of autistic spectrum disorders (ASD) patients' brains confirm existence of very early developmental deficits. In congenital and chronic murine toxoplasmosis several cerebral anomalies also have been reported, and worldwide, approximately two billion people are chronically infected with T. "gondii"…

  20. Professor Camillo Negro's Neuropathological Films.

    Science.gov (United States)

    Chiò, Adriano; Gianetto, Claudia; Dagna, Stella

    2016-01-01

    Camillo Negro, Professor in Neurology at the University of Torino, was a pioneer of scientific film. From 1906 to 1908, with the help of his assistant Giuseppe Roasenda and in collaboration with Roberto Omegna, one of the most experienced cinematographers in Italy, he filmed some of his patients for scientific and educational purposes. During the war years, he continued his scientific film project at the Military Hospital in Torino, filming shell-shocked soldiers. In autumn 2011, the Museo Nazionale del Cinema, in partnership with the Faculty of Neurosciences of the University of Torino, presented a new critical edition of the neuropathological films directed by Negro. The Museum's collection also includes 16 mm footage probably filmed in 1930 by Doctor Fedele Negro, Camillo's son. One of these films is devoted to celebrating the effects of the so-called "Bulgarian cure" on Parkinson's disease.

  1. Human object-similarity judgments reflect and transcend the primate-IT object representation

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    Marieke eMur

    2013-03-01

    Full Text Available Primate inferior temporal (IT cortex is thought to contain a high-level representation of objects at the interface between vision and semantics. This suggests that the perceived similarity of real-world objects might be predicted from the IT representation. Here we show that objects that elicit similar activity patterns in human IT tend to be judged as similar by humans. The IT representation explained the human judgments better than early visual cortex, other ventral stream regions, and a range of computational models. Human similarity judgments exhibited category clusters that reflected several categorical divisions that are prevalent in the IT representation of both human and monkey, including the animate/inanimate and the face/body division. Human judgments also reflected the within-category representation of IT. However, the judgments transcended the IT representation in that they introduced additional categorical divisions. In particular, human judgments emphasized human-related additional divisions between human and nonhuman animals and between man-made and natural objects. Human IT was more similar to monkey IT than to human judgments. One interpretation is that IT has evolved visual feature detectors that distinguish between animates and inanimates and between faces and bodies because these divisions are fundamental to survival and reproduction for all primate species, and that other brain systems serve to more flexibly introduce species-dependent and evolutionarily more recent divisions.

  2. Region of eye contact of humanoid Nao robot is similar to that of a human

    NARCIS (Netherlands)

    Cuijpers, R.H.; Pol, van der D.; Herrmann, G.; Pearson, M.J.; Lenz, A.; Bremner, P.; Spiers, A.; Leonards, U.

    2013-01-01

    Eye contact is an important social cue in human-human interaction, but it is unclear how easily it carries over to humanoid robots. In this study we investigated whether the tolerance of making eye contact is similar for the Nao robot as compared to human lookers. We measured the region of eye

  3. Histologic examination of the rat central nervous system after intrathecal administration of human beta-endorphin

    DEFF Research Database (Denmark)

    Hée, P.; Klinken, Leif; Ballegaard, Martin

    1992-01-01

    Neuropathology, analgesics - intrathecal, central nervous system, histology, human beta-endorphin, toxicity......Neuropathology, analgesics - intrathecal, central nervous system, histology, human beta-endorphin, toxicity...

  4. Neuroanatomy and neuropathology associated with Korsakoff's syndrome.

    Science.gov (United States)

    Kril, Jillian J; Harper, Clive G

    2012-06-01

    Although the neuropathology of Korsakoff's syndrome (KS) was first described well over a century ago and the characteristic brain pathology does not pose a diagnostic challenge to pathologists, there is still controversy over the neuroanatomical substrate of the distinctive memory impairment in these patients. Cohort studies of KS suggest a central role for the mammillary bodies and mediodorsal thalamus, and quantitative studies suggest additional damage to the anterior thalamus is required. Rare cases of KS caused by pathologies other than those of nutritional origin provide support for the role of the anterior thalamus and mammillary bodies. Taken together the evidence to date shows that damage to the thalamus and hypothalamus is required, in particular the anterior thalamic nucleus and the medial mammillary nucleus of the hypothalamus. As these nuclei form part of wider memory circuits, damage to the inter-connecting white matter tracts can also result in a similar deficit as direct damage to the nuclei. Although these nuclei and their connections appear to be the primary site of damage, input from other brain regions within the circuits, such as the frontal cortex and hippocampus, or more distant regions, including the cerebellum and amygdala, may have a modulatory role on memory function. Further studies to confirm the precise site(s) and extend of brain damage necessary for the memory impairment of KS are required.

  5. Prediction of the human response time with the similarity and quantity of information

    International Nuclear Information System (INIS)

    Lee, Sungjin; Heo, Gyunyoung; Chang, Soon Heung

    2006-01-01

    Memory is one of brain processes that are important when trying to understand how people process information. Although a large number of studies have been made on the human performance, little is known about the similarity effect in human performance. The purpose of this paper is to propose and validate the quantitative and predictive model on the human response time in the user interface with the concept of similarity. However, it is not easy to explain the human performance with only similarity or information amount. We are confronted by two difficulties: making the quantitative model on the human response time with the similarity and validating the proposed model by experimental work. We made the quantitative model based on the Hick's law and the law of practice. In addition, we validated the model with various experimental conditions by measuring participants' response time in the environment of computer-based display. Experimental results reveal that the human performance is improved by the user interface's similarity. We think that the proposed model is useful for the user interface design and evaluation phases

  6. Similarity of hydrolyzing activity of human and rat small intestinal disaccharidases

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    Oku T

    2011-06-01

    Full Text Available Tsuneyuki Oku¹, Kenichi Tanabe¹, Shigeharu Ogawa², Naoki Sadamori¹, Sadako Nakamura¹¹Graduate School of Human Health Science, University of Nagasaki, Siebold, Nagayo, Japan; ²Juzenkai Hospital, Kagomachi, Nagasaki, JapanBackground: The purpose of this study was to clarify whether it is possible to extrapolate results from studies of the hydrolyzing activity of disaccharidases from rats to humans.Materials and methods: We measured disaccharidase activity in humans and rats using identical preparation and assay methods, and investigated the similarity in hydrolyzing activity. Small intestinal samples without malignancy were donated by five patients who had undergone bladder tumor surgery, and homogenates were prepared to measure disaccharidase activity. Adult rat homogenates were prepared using small intestine.Results: Maltase activity was the highest among the five disaccharidases, followed by sucrase and then palatinase in humans and rats. Trehalase activity was slightly lower than that of palatinase in humans and was similar to that of sucrase in rats. Lactase activity was the lowest in humans, but was similar to that of palatinase in rats. Thus, the hydrolyzing activity of five disaccharidases was generally similar in humans and rats. The relative activity of sucrose and palatinase versus maltase was generally similar between humans and rats. The ratio of rat to human hydrolyzing activity of maltase, sucrase, and palatinase was 1.9–3.1, but this was not a significant difference. Leaf extract from Morus alba strongly inhibited the activity of maltase, sucrase, and palatinase, but not trehalase and lactase, and the degree of inhibition was similar in humans and rats. L-arabinose mildly inhibited sucrase activity, but hardly inhibited the activity of maltase, palatinase, trehalase and lactase in humans and rats. The digestibility of 1-kestose, galactosylsucrose, and panose by small intestinal enzymes was very similar between humans and

  7. Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis

    Science.gov (United States)

    Swindell, William R.; Johnston, Andrew; Carbajal, Steve; Han, Gangwen; Wohn, Christian; Lu, Jun; Xing, Xianying; Nair, Rajan P.; Voorhees, John J.; Elder, James T.; Wang, Xiao-Jing; Sano, Shigetoshi; Prens, Errol P.; DiGiovanni, John; Pittelkow, Mark R.; Ward, Nicole L.; Gudjonsson, Johann E.

    2011-01-01

    Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis. PMID:21483750

  8. Predictive modeling of human perception subjectivity: feasibility study of mammographic lesion similarity

    Science.gov (United States)

    Xu, Songhua; Hudson, Kathleen; Bradley, Yong; Daley, Brian J.; Frederick-Dyer, Katherine; Tourassi, Georgia

    2012-02-01

    The majority of clinical content-based image retrieval (CBIR) studies disregard human perception subjectivity, aiming to duplicate the consensus expert assessment of the visual similarity on example cases. The purpose of our study is twofold: i) discern better the extent of human perception subjectivity when assessing the visual similarity of two images with similar semantic content, and (ii) explore the feasibility of personalized predictive modeling of visual similarity. We conducted a human observer study in which five observers of various expertise were shown ninety-nine triplets of mammographic masses with similar BI-RADS descriptors and were asked to select the two masses with the highest visual relevance. Pairwise agreement ranged between poor and fair among the five observers, as assessed by the kappa statistic. The observers' self-consistency rate was remarkably low, based on repeated questions where either the orientation or the presentation order of a mass was changed. Various machine learning algorithms were explored to determine whether they can predict each observer's personalized selection using textural features. Many algorithms performed with accuracy that exceeded each observer's self-consistency rate, as determined using a cross-validation scheme. This accuracy was statistically significantly higher than would be expected by chance alone (two-tailed p-value ranged between 0.001 and 0.01 for all five personalized models). The study confirmed that human perception subjectivity should be taken into account when developing CBIR-based medical applications.

  9. Updating neuropathology and neuropharmacology of monoaminergic systems.

    Science.gov (United States)

    Ramsay, Rona R; De Deurwaerdère, Philippe; Di Giovanni, Giuseppe

    2016-07-01

    This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc. © 2016 The British Pharmacological Society.

  10. Pollen Allergies in Humans and their Dogs, Cats and Horses: Differences and Similarities

    OpenAIRE

    Jensen-Jarolim, Erika; Einhorn, Lukas; Herrmann, Ina; Thalhammer, Johann G; Panakova, Lucia

    2015-01-01

    Both humans and their most important domestic animals harbor IgE and a similar IgE receptor repertoire and expression pattern. The same cell types are also involved in the triggering or regulation of allergies, such as mast cells, eosinophils or T-regulatory cells. Translational clinical studies in domestic animals could therefore help cure animal allergies and at the same time gather knowledge relevant to human patients. Dogs, cats and horses may spontaneously and to different extents develo...

  11. The Human Semicircular Canals Orientation Is More Similar to the Bonobos than to the Chimpanzees

    Science.gov (United States)

    El Khoury, Marwan; Braga, José; Dumoncel, Jean; Nancy, Javotte; Esclassan, Remi; Vaysse, Frederic

    2014-01-01

    For some traits, the human genome is more closely related to either the bonobo or the chimpanzee genome than they are to each other. Therefore, it becomes crucial to understand whether and how morphostructural differences between humans, chimpanzees and bonobos reflect the well known phylogeny. Here we comparatively investigated intra and extra labyrinthine semicircular canals orientation using 260 computed tomography scans of extant humans (Homo sapiens), bonobos (Pan paniscus) and chimpanzees (Pan troglodytes). Humans and bonobos proved more similarities between themselves than with chimpanzees. This finding did not fit with the well established chimpanzee – bonobo monophyly. One hypothesis was convergent evolution in which bonobos and humans produce independently similar phenotypes possibly in response to similar selective pressures that may be associated with postural adaptations. Another possibility was convergence following a “random walk” (Brownian motion) evolutionary model. A more parsimonious explanation was that the bonobo-human labyrinthine shared morphology more closely retained the ancestral condition with chimpanzees being subsequently derived. Finally, these results might be a consequence of genetic diversity and incomplete lineage sorting. The remarkable symmetry of the Semicircular Canals was the second major finding of this article with possible applications in taphonomy. It has the potential to investigate altered fossils, inferring the probability of post-mortem deformation which can lead to difficulties in understanding taxonomic variation, phylogenetic relationships, and functional morphology. PMID:24710502

  12. The human semicircular canals orientation is more similar to the bonobos than to the chimpanzees.

    Directory of Open Access Journals (Sweden)

    Marwan El Khoury

    Full Text Available For some traits, the human genome is more closely related to either the bonobo or the chimpanzee genome than they are to each other. Therefore, it becomes crucial to understand whether and how morphostructural differences between humans, chimpanzees and bonobos reflect the well known phylogeny. Here we comparatively investigated intra and extra labyrinthine semicircular canals orientation using 260 computed tomography scans of extant humans (Homo sapiens, bonobos (Pan paniscus and chimpanzees (Pan troglodytes. Humans and bonobos proved more similarities between themselves than with chimpanzees. This finding did not fit with the well established chimpanzee - bonobo monophyly. One hypothesis was convergent evolution in which bonobos and humans produce independently similar phenotypes possibly in response to similar selective pressures that may be associated with postural adaptations. Another possibility was convergence following a "random walk" (Brownian motion evolutionary model. A more parsimonious explanation was that the bonobo-human labyrinthine shared morphology more closely retained the ancestral condition with chimpanzees being subsequently derived. Finally, these results might be a consequence of genetic diversity and incomplete lineage sorting. The remarkable symmetry of the Semicircular Canals was the second major finding of this article with possible applications in taphonomy. It has the potential to investigate altered fossils, inferring the probability of post-mortem deformation which can lead to difficulties in understanding taxonomic variation, phylogenetic relationships, and functional morphology.

  13. From sweeping to the caress: similarities and discrepancies between human and non-human primates' pleasant touch

    Directory of Open Access Journals (Sweden)

    Laura Clara Grandi

    2016-09-01

    Full Text Available Affective touch plays a key role in affiliative behavior, offering a mechanism for the formation and maintenance of social bonds among conspecifics, both in humans and non-human primates. Furthermore, it has been speculated that the CT fiber system is a specific coding channel for affiliative touch that occurs during skin-to-skin interactions with conspecifics. In humans, this touch is commonly referred to as the caress, and its correlation with the CT fiber system has been widely demonstrated. It has been hypothesized that the sweeping touch that occurs during grooming in non-human primates may modulate the CT fibers, with recent preliminary studies on rhesus monkeys supporting this hypothesis. The present mini-review proposes a comparison between the pleasant touch, caress and sweeping of humans and non-human primates, respectively. The currently available data was therefore reviewed regarding i the correlation between pleasant touch and CT fibers both in humans and non-human primates, ii the autonomic effects, iii the encoding at the central nervous system, iv the development from early life to adulthood, and v the potential applications of pleasant touch in the daily lives of both humans and non-human primates. Moreover, by considering both the similarities and discrepancies between the human caress and non-human primate sweeping, a possible evolutionary mechanism can be proposed that has developed from sweeping as a utilitarian action with affiliative meaning among monkeys, to the caress as a purely affective gesture associated with humans.

  14. Active site similarity between human and Plasmodium falciparum phosphodiesterases: considerations for antimalarial drug design

    Science.gov (United States)

    Howard, Brittany L.; Thompson, Philip E.; Manallack, David T.

    2011-08-01

    The similarity between Plasmodium falciparum phosphodiesterase enzymes ( PfPDEs) and their human counterparts have been examined and human PDE9A was found to be a suitable template for the construction of homology models for each of the four PfPDE isoforms. In contrast, the architecture of the active sites of each model was most similar to human PDE1. Molecular docking was able to model cyclic guanosine monophosphate (cGMP) substrate binding in each case but a docking mode supporting cyclic adenosine monophosphate (cAMP) binding could not be found. Anticipating the potential of PfPDE inhibitors as anti-malarial drugs, a range of reported PDE inhibitors including zaprinast and sildenafil were docked into the model of PfPDEα. The results were consistent with their reported biological activities, and the potential of PDE1/9 inhibitor analogues was also supported by docking.

  15. Neuropathological assessment and validation of mouse models for Alzheimer's disease: applying NIA-AA guidelines

    Directory of Open Access Journals (Sweden)

    C. Dirk Keene

    2016-06-01

    Full Text Available Dozens of transgenic mouse models, generally based on mutations associated with familial Alzheimer's disease (AD, have been developed, in part, for preclinical testing of candidate AD therapies. However, none of these models has successfully predicted the clinical efficacy of drugs for treating AD patients. Therefore, development of more translationally relevant AD mouse models remains a critical unmet need in the field. A concept not previously implemented in AD preclinical drug testing is the use of mouse lines that have been validated for neuropathological features of human AD. Current thinking suggests that amyloid plaque and neurofibrillary tangle deposition is an essential component for accurate modeling of AD. Therefore, the AD translational paradigm would require pathologic Aβ and tau deposition, a disease-relevant distribution of plaques and tangles, and a pattern of disease progression of Aβ and tau isoforms similar to the neuropathological features found in the brains of AD patients. Additional parameters useful to evaluate parallels between AD and animal models would include 1 cerebrospinal fluid (CSF AD biomarker changes with reduced Aβ and increased phospho-tau/tau; 2 structural and functional neuroimaging patterns including MRI hippocampal atrophy, fluorodeoxyglucose (FDG, and amyloid/tau PET alterations in activity and/or patterns of pathologic peptide deposition and distribution; and 3 cognitive impairment with emphasis on spatial learning and memory to distinguish presymptomatic and symptomatic mice at specific ages. A validated AD mouse model for drug testing would likely show tau-related neurofibrillary degeneration following Aβ deposition and demonstrate changes in pathology, CSF analysis, and neuroimaging that mirror human AD. Development of the ideal model would revolutionize the ability to establish the translational value of AD mouse models and serve as a platform for discussions about national phenotyping guidelines

  16. A Quantitative Comparison of the Similarity between Genes and Geography in Worldwide Human Populations

    Science.gov (United States)

    Wang, Chaolong; Zöllner, Sebastian; Rosenberg, Noah A.

    2012-01-01

    Multivariate statistical techniques such as principal components analysis (PCA) and multidimensional scaling (MDS) have been widely used to summarize the structure of human genetic variation, often in easily visualized two-dimensional maps. Many recent studies have reported similarity between geographic maps of population locations and MDS or PCA maps of genetic variation inferred from single-nucleotide polymorphisms (SNPs). However, this similarity has been evident primarily in a qualitative sense; and, because different multivariate techniques and marker sets have been used in different studies, it has not been possible to formally compare genetic variation datasets in terms of their levels of similarity with geography. In this study, using genome-wide SNP data from 128 populations worldwide, we perform a systematic analysis to quantitatively evaluate the similarity of genes and geography in different geographic regions. For each of a series of regions, we apply a Procrustes analysis approach to find an optimal transformation that maximizes the similarity between PCA maps of genetic variation and geographic maps of population locations. We consider examples in Europe, Sub-Saharan Africa, Asia, East Asia, and Central/South Asia, as well as in a worldwide sample, finding that significant similarity between genes and geography exists in general at different geographic levels. The similarity is highest in our examples for Asia and, once highly distinctive populations have been removed, Sub-Saharan Africa. Our results provide a quantitative assessment of the geographic structure of human genetic variation worldwide, supporting the view that geography plays a strong role in giving rise to human population structure. PMID:22927824

  17. A quantitative comparison of the similarity between genes and geography in worldwide human populations.

    Science.gov (United States)

    Wang, Chaolong; Zöllner, Sebastian; Rosenberg, Noah A

    2012-08-01

    Multivariate statistical techniques such as principal components analysis (PCA) and multidimensional scaling (MDS) have been widely used to summarize the structure of human genetic variation, often in easily visualized two-dimensional maps. Many recent studies have reported similarity between geographic maps of population locations and MDS or PCA maps of genetic variation inferred from single-nucleotide polymorphisms (SNPs). However, this similarity has been evident primarily in a qualitative sense; and, because different multivariate techniques and marker sets have been used in different studies, it has not been possible to formally compare genetic variation datasets in terms of their levels of similarity with geography. In this study, using genome-wide SNP data from 128 populations worldwide, we perform a systematic analysis to quantitatively evaluate the similarity of genes and geography in different geographic regions. For each of a series of regions, we apply a Procrustes analysis approach to find an optimal transformation that maximizes the similarity between PCA maps of genetic variation and geographic maps of population locations. We consider examples in Europe, Sub-Saharan Africa, Asia, East Asia, and Central/South Asia, as well as in a worldwide sample, finding that significant similarity between genes and geography exists in general at different geographic levels. The similarity is highest in our examples for Asia and, once highly distinctive populations have been removed, Sub-Saharan Africa. Our results provide a quantitative assessment of the geographic structure of human genetic variation worldwide, supporting the view that geography plays a strong role in giving rise to human population structure.

  18. Biology, diagnosis and treatment of canine appendicular osteosarcoma: similarities and differences with human osteosarcoma.

    Science.gov (United States)

    Morello, Emanuela; Martano, Marina; Buracco, Paolo

    2011-09-01

    Osteosarcoma (OSA) is the most common primary bone tumour in dogs. The appendicular locations are most frequently involved and large to giant breed dogs are commonly affected, with a median age of 7-8 years. OSA is a locally invasive neoplasm with a high rate of metastasis, mostly to the lungs. Due to similarities in biology and treatment of OSA in dogs and humans, canine OSA represents a valid and important tumour model. Differences between canine and human OSAs include the age of occurrence (OSA is most commonly an adolescent disease in humans), localisation (the stifle is the most common site of localisation in humans) and limited use of neoadjuvant chemotherapy in canine OSA. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Dog experts' brains distinguish socially relevant body postures similarly in dogs and humans.

    Science.gov (United States)

    Kujala, Miiamaaria V; Kujala, Jan; Carlson, Synnöve; Hari, Riitta

    2012-01-01

    We read conspecifics' social cues effortlessly, but little is known about our abilities to understand social gestures of other species. To investigate the neural underpinnings of such skills, we used functional magnetic resonance imaging to study the brain activity of experts and non-experts of dog behavior while they observed humans or dogs either interacting with, or facing away from a conspecific. The posterior superior temporal sulcus (pSTS) of both subject groups dissociated humans facing toward each other from humans facing away, and in dog experts, a distinction also occurred for dogs facing toward vs. away in a bilateral area extending from the pSTS to the inferior temporo-occipital cortex: the dissociation of dog behavior was significantly stronger in expert than control group. Furthermore, the control group had stronger pSTS responses to humans than dogs facing toward a conspecific, whereas in dog experts, the responses were of similar magnitude. These findings suggest that dog experts' brains distinguish socially relevant body postures similarly in dogs and humans.

  20. Similarities between Salmonella Enteritidis isolated from humans and captive wild animals in South Africa.

    Science.gov (United States)

    Smith, Anthony M; Ismail, Husna; Henton, Maryke M; Keddy, Karen H

    2014-12-15

    Salmonella is well recognized as an aetiological agent of gastrointestinal and diarrhoeal disease. Salmonella enterica serotype Enteritidis (Salmonella Enteritidis) is one of the commonest serotypes associated with foodborne illness. In South Africa, we compared Salmonella Enteritidis strains isolated from humans with gastroenteritis and strains isolated from captive wild animals, between June 2011 and July 2012. Bacteria were phenotypically characterized using standard microbiological techniques. Genotypic relatedness of isolates was investigated by pulsed-field gel electrophoresis (PFGE) analysis. a diversity of 27 PFGE patterns amongst 196 human non-invasive isolates was shown; two PFGE patterns predominated and accounted for 74% of all human isolates. Human isolates showed a 12% prevalence rate for nalidixic acid resistance. Animal isolates from 5 different sources were investigated. With the exception of an isolate from a ground hornbill, all animal isolates (jaguar, crocodile, lion and poultry) showed PFGE pattern matches to a human isolate. Animal isolates showed susceptibility to all antimicrobial agents tested, with the exception of nalidixic acid resistance in isolates from the lion and poultry source. Our data showed similarities between Salmonella Enteritidis strains isolated from humans and captive wild animals, suggesting a probable common source for strains from humans and animals.

  1. The future of neuropathology in childhood.

    Science.gov (United States)

    Rorke, L B

    2000-11-01

    The current state of knowledge of pediatric neuropathology is based upon a rich historical heritage dating back many centuries and representing the genius of many people, although, relatively speaking, little specific attention was paid to the unique issues relating to infants and children. Aside from descriptions of morphological features of disease (including tumors), advances in understanding basic pathogenetic mechanisms have flowered only in the recent past. Most exciting has been the progress in molecular biology and genetics, which has yielded a phenomenal bank of information in a short time, uncovering details of genes involved in development of the nervous system and specifically associated with various types of tumors. The future of pediatric neuropathology requires partnership with molecular geneticists whose studies hold promise of defining morphology.

  2. Molecular Neuropathology of TDP-43 Proteinopathies

    Directory of Open Access Journals (Sweden)

    Manuela Neumann

    2009-01-01

    Full Text Available The identification of TDP-43 as the major component of the pathologic inclusions in most forms of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U and amyotrophic lateral sclerosis (ALS resolved a long-standing enigma concerning the nature of the ubiquitinated disease protein under these conditions. Anti-TDP-43 immunohistochemistry and the recent development of novel tools, such as phosphorylation-specific TDP-43 antibodies, have increased our knowledge about the spectrum of pathological changes associated with FTLD-U and ALS and moreover, facilitated the neuropathological routine diagnosis of these conditions. This review summarizes the recent advances in our understanding on the molecular neuropathology and pathobiology of TDP-43 in FTLD and ALS.

  3. Structural similarities and differences between the human and the mouse pancreas

    Science.gov (United States)

    Dolenšek, Jurij; Rupnik, Marjan Slak; Stožer, Andraž

    2015-01-01

    Mice remain the most studied animal model in pancreas research. Since the findings of this research are typically extrapolated to humans, it is important to understand both similarities and differences between the 2 species. Beside the apparent difference in size and macroscopic organization of the organ in the 2 species, there are a number of less evident and only recently described differences in organization of the acinar and ductal exocrine tissue, as well as in the distribution, composition, and architecture of the endocrine islets of Langerhans. Furthermore, the differences in arterial, venous, and lymphatic vessels, as well as innervation are potentially important. In this article, the structure of the human and the mouse pancreas, together with the similarities and differences between them are reviewed in detail in the light of conceivable repercussions for basic research and clinical application. PMID:26030186

  4. Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

    KAUST Repository

    Hoehndorf, Robert

    2015-06-08

    Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.

  5. Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

    Science.gov (United States)

    Hoehndorf, Robert; Schofield, Paul N.; Gkoutos, Georgios V.

    2015-06-01

    Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.

  6. Social Trust and Value Similarity: the Relationship between Social Trust and Human Values in Europe

    Directory of Open Access Journals (Sweden)

    Mai Beilmann

    2015-12-01

    Full Text Available The purpose of the current paper is to test whether value similarity may foster social trust in society and whether people have higher levels of social trust when they emphasise the same values that prevail in their country. The relationship between social trust and human values was examined in a sample of 51,308 people across 29 European countries using data from the European Social Survey round 6. Results suggest that value similarity is more important in generating individual level social trust in countries where the overall levels of social trust are higher. There is a stronger positive relationship between value similarity and social trust in Scandinavian countries, which have high social trust levels, while in countries with a low level of social trust, congruity of the personal value structure with the country level value structure tends to decrease the individuals trustfulness

  7. Global similarity and local divergence in human and mouse gene co-expression networks

    Directory of Open Access Journals (Sweden)

    Koonin Eugene V

    2006-09-01

    Full Text Available Abstract Background A genome-wide comparative analysis of human and mouse gene expression patterns was performed in order to evaluate the evolutionary divergence of mammalian gene expression. Tissue-specific expression profiles were analyzed for 9,105 human-mouse orthologous gene pairs across 28 tissues. Expression profiles were resolved into species-specific coexpression networks, and the topological properties of the networks were compared between species. Results At the global level, the topological properties of the human and mouse gene coexpression networks are, essentially, identical. For instance, both networks have topologies with small-world and scale-free properties as well as closely similar average node degrees, clustering coefficients, and path lengths. However, the human and mouse coexpression networks are highly divergent at the local level: only a small fraction ( Conclusion The dissonance between global versus local network divergence suggests that the interspecies similarity of the global network properties is of limited biological significance, at best, and that the biologically relevant aspects of the architectures of gene coexpression are specific and particular, rather than universal. Nevertheless, there is substantial evolutionary conservation of the local network structure which is compatible with the notion that gene coexpression networks are subject to purifying selection.

  8. Human-based percussion and self-similarity detection in electroacoustic music

    Science.gov (United States)

    Mills, John Anderson, III

    Electroacoustic music is music that uses electronic technology for the compositional manipulation of sound, and is a unique genre of music for many reasons. Analyzing electroacoustic music requires special measures, some of which are integrated into the design of a preliminary percussion analysis tool set for electroacoustic music. This tool set is designed to incorporate the human processing of music and sound. Models of the human auditory periphery are used as a front end to the analysis algorithms. The audio properties of percussivity and self-similarity are chosen as the focus because these properties are computable and informative. A collection of human judgments about percussion was undertaken to acquire clearly specified, sound-event dimensions that humans use as a percussive cue. A total of 29 participants was asked to make judgments about the percussivity of 360 pairs of synthesized snare-drum sounds. The grouped results indicate that of the dimensions tested rise time is the strongest cue for percussivity. String resonance also has a strong effect, but because of the complex nature of string resonance, it is not a fundamental dimension of a sound event. Gross spectral filtering also has an effect on the judgment of percussivity but the effect is weaker than for rise time and string resonance. Gross spectral filtering also has less effect when the stronger cue of rise time is modified simultaneously. A percussivity-profile algorithm (PPA) is designed to identify those instants in pieces of music that humans also would identify as percussive. The PPA is implemented using a time-domain, channel-based approach and psychoacoustic models. The input parameters are tuned to maximize performance at matching participants' choices in the percussion-judgment collection. After the PPA is tuned, the PPA then is used to analyze pieces of electroacoustic music. Real electroacoustic music introduces new challenges for the PPA, though those same challenges might affect

  9. Predicting human age using regional morphometry and inter-regional morphological similarity

    Science.gov (United States)

    Wang, Xun-Heng; Li, Lihua

    2016-03-01

    The goal of this study is predicting human age using neuro-metrics derived from structural MRI, as well as investigating the relationships between age and predictive neuro-metrics. To this end, a cohort of healthy subjects were recruited from 1000 Functional Connectomes Project. The ages of the participations were ranging from 7 to 83 (36.17+/-20.46). The structural MRI for each subject was preprocessed using FreeSurfer, resulting in regional cortical thickness, mean curvature, regional volume and regional surface area for 148 anatomical parcellations. The individual age was predicted from the combination of regional and inter-regional neuro-metrics. The prediction accuracy is r = 0.835, p Pearson correlation coefficient between predicted ages and actual ages. Moreover, the LASSO linear regression also found certain predictive features, most of which were inter-regional features. The turning-point of the developmental trajectories in human brain was around 40 years old based on regional cortical thickness. In conclusion, structural MRI could be potential biomarkers for the aging in human brain. The human age could be successfully predicted from the combination of regional morphometry and inter-regional morphological similarity. The inter-regional measures could be beneficial to investigating human brain connectome.

  10. Kinematic and Gait Similarities between Crawling Human Infants and Other Quadruped Mammals

    Science.gov (United States)

    Righetti, Ludovic; Nylén, Anna; Rosander, Kerstin; Ijspeert, Auke Jan

    2015-01-01

    Crawling on hands and knees is an early pattern of human infant locomotion, which offers an interesting way of studying quadrupedalism in one of its simplest form. We investigate how crawling human infants compare to other quadruped mammals, especially primates. We present quantitative data on both the gait and kinematics of seven 10-month-old crawling infants. Body movements were measured with an optoelectronic system giving precise data on 3-dimensional limb movements. Crawling on hands and knees is very similar to the locomotion of non-human primates in terms of the quite protracted arm at touch-down, the coordination between the spine movements in the lateral plane and the limbs, the relatively extended limbs during locomotion and the strong correlation between stance duration and speed of locomotion. However, there are important differences compared to primates, such as the choice of a lateral-sequence walking gait, which is similar to most non-primate mammals and the relatively stiff elbows during stance as opposed to the quite compliant gaits of primates. These finding raise the question of the role of both the mechanical structure of the body and neural control on the determination of these characteristics. PMID:25709597

  11. Neuropathology of amyotrophic lateral sclerosis and its variants”

    Science.gov (United States)

    Saberi, Shahram; Stauffer, Jennifer E.; Schulte, Derek J.; Ravits, John

    2015-01-01

    Summary Amyotrophic lateral sclerosis (ALS) is a clinical syndrome named for its neuropathological hallmark: degeneration of motor neurons in the spinal anterior horn and motor cortex and loss of axons in the lateral columns of the spinal cord. The signature neuropathological molecular signature common to almost all sporadic ALS and most familial ALS is TDP-43 immunoreactive neuronal cytoplasmic inclusions. The neuropathological and molecular neuropathological features of ALS variants primarly lateral sclerosis and progressive muscular atrophy are less certain, but also appear to share the primary features of ALS. A number of genetic causes including mutations in SOD1, FUS, and C9orf72 comprise a disease spectrum and all demonstrate distinctive molecular and neuropathological signatures. Neuropathology will continue to play to a key role in solving the puzzle of ALS pathogenesis. PMID:26515626

  12. Pollen Allergies in Humans and their Dogs, Cats and Horses: Differences and Similarities.

    Science.gov (United States)

    Jensen-Jarolim, Erika; Einhorn, Lukas; Herrmann, Ina; Thalhammer, Johann G; Panakova, Lucia

    2015-01-01

    Both humans and their most important domestic animals harbor IgE and a similar IgE receptor repertoire and expression pattern. The same cell types are also involved in the triggering or regulation of allergies, such as mast cells, eosinophils or T-regulatory cells. Translational clinical studies in domestic animals could therefore help cure animal allergies and at the same time gather knowledge relevant to human patients. Dogs, cats and horses may spontaneously and to different extents develop immediate type symptoms to pollen allergens. The skin, nasal and bronchial reactions, as well as chronic skin lesions due to pollen are in principle comparable to human patients. Pollen of various species most often causes allergic rhinitis in human patients, whereas in dogs it elicits predominantly eczematous lesions (canine atopic dermatitis), in horses recurrent airway obstruction or hives as well as pruritic dermatitis, and in cats bronchial asthma and so-called cutaneous reactive patterns (eosinophilic granuloma complex, head and neck pruritus, symmetric self-induced alopecia). In human allergy-specific IgE detection, skin tests or other allergen provocation tests should be completed. In contrast, in animals IgE and dermal tests are regarded as equally important and may even replace each other. However, for practical and economic reasons intradermal tests are most commonly performed in a specialized practice. As in humans, in dogs, cats and horses allergen immunotherapy leads to significant improvement of the clinical symptoms. The collected evidence suggests that canines, felines and equines, with their spontaneous allergies, are attractive model patients for translational studies.

  13. Favorable ecological circumstances promote life expectancy in chimpanzees similar to that of human hunter-gatherers.

    Science.gov (United States)

    Wood, Brian M; Watts, David P; Mitani, John C; Langergraber, Kevin E

    2017-04-01

    Demographic data on wild chimpanzees are crucial for understanding the evolution of chimpanzee and hominin life histories, but most data come from populations affected by disease outbreaks and anthropogenic disturbance. We present survivorship data from a relatively undisturbed and exceptionally large community of eastern chimpanzees (Pan troglodytes schweinfurthii) at Ngogo, Kibale National Park, Uganda. We monitored births, deaths, immigrations, and emigrations in the community between 1995 and 2016. Using known and estimated ages, we calculated survivorship curves for the whole community, for males and females separately, and for individuals ≤2 years old when identified. We used a novel method to address age estimation error by calculating stochastic survivorship curves. We compared Ngogo life expectancy, survivorship, and mortality rates to those from other chimpanzee communities and human hunter-gatherers. Life expectancy at birth for both sexes combined was 32.8 years, far exceeding estimates of chimpanzee life expectancy in other communities, and falling within the range of human hunter-gatherers (i.e., 27-37 years). Overall, the pattern of survivorship at Ngogo was more similar to that of human hunter-gatherers than to other chimpanzee communities. Maximum lifespan for the Ngogo chimpanzees, however, was similar to that reported at other chimpanzee research sites and was less than that of human-hunter gatherers. The absence of predation by large carnivores may contribute to some of the higher survivorship at Ngogo, but this cannot explain the much higher survivorship at Ngogo than at Kanyawara, another chimpanzee community in the same forest, which also lacks large carnivores. Higher survivorship at Ngogo appears to be an adaptive response to a food supply that is more abundant and varies less than that of Kanyawara. Future analyses of hominin life history evolution should take these results into account. Copyright © 2017 Elsevier Ltd. All rights

  14. Coffin-Siris syndrome. Neuropathologic findings.

    Science.gov (United States)

    DeBassio, W A; Kemper, T L; Knoefel, J E

    1985-04-01

    We studied the neuropathologic features of a patient with Coffin-Siris syndrome. Two previously reported cases showed Dandy-Walker (D-W) malformations. In the present case there was no evidence of D-W malformation; instead there were hindbrain abnormalities of inferior and medial accessory olives, large arcuate nuclei, heterotopic olivary nuclei, and heterotopic nuclei in the white matter of the cerebellum. Although the hindbrain abnormalities in this case are different from those previously reported, they all have in common an intimate developmental relationship with the same embryological areas. This study suggests that the Coffin-Siris syndrome is a neurocutaneous disorder with hindbrain abnormalities in cerebellum and brain stem.

  15. Faithful representation of similarities among three-dimensional shapes in human vision.

    Science.gov (United States)

    Cutzu, F; Edelman, S

    1996-01-01

    Efficient and reliable classification of visual stimuli requires that their representations reside a low-dimensional and, therefore, computationally manageable feature space. We investigated the ability of the human visual system to derive such representations from the sensory input-a highly nontrivial task, given the million or so dimensions of the visual signal at its entry point to the cortex. In a series of experiments, subjects were presented with sets of parametrically defined shapes; the points in the common high-dimensional parameter space corresponding to the individual shapes formed regular planar (two-dimensional) patterns such as a triangle, a square, etc. We then used multidimensional scaling to arrange the shapes in planar configurations, dictated by their experimentally determined perceived similarities. The resulting configurations closely resembled the original arrangements of the stimuli in the parameter space. This achievement of the human visual system was replicated by a computational model derived from a theory of object representation in the brain, according to which similarities between objects, and not the geometry of each object, need to be faithfully represented. Images Fig. 3 PMID:8876260

  16. Humans, geometric similarity and the Froude number: is ''reasonably close'' really close enough?

    Science.gov (United States)

    Kramer, Patricia Ann; Sylvester, Adam D

    2013-02-15

    Understanding locomotor energetics is imperative, because energy expended during locomotion, a requisite feature of primate subsistence, is lost to reproduction. Although metabolic energy expenditure can only be measured in extant species, using the equations of motion to calculate mechanical energy expenditure offers unlimited opportunities to explore energy expenditure, particularly in extinct species on which empirical experimentation is impossible. Variability, either within or between groups, can manifest as changes in size and/or shape. Isometric scaling (or geometric similarity) requires that all dimensions change equally among all individuals, a condition that will not be met in naturally developing populations. The Froude number (Fr), with lower limb (or hindlimb) length as the characteristic length, has been used to compensate for differences in size, but does not account for differences in shape.To determine whether or not shape matters at the intraspecific level, we used a mechanical model that had properties that mimic human variation in shape. We varied crural index and limb segment circumferences (and consequently, mass and inertial parameters) among nine populations that included 19 individuals that were of different size. Our goal in the current work is to understand whether shape variation changes mechanical energy sufficiently enough to make shape a critical factor in mechanical and metabolic energy assessments.Our results reaffirm that size does not affect mass-specific mechanical cost of transport (Alexander and Jayes, 1983) among geometrically similar individuals walking at equal Fr. The known shape differences among modern humans, however, produce sufficiently large differences in internal and external work to account for much of the observed variation in metabolic energy expenditure, if mechanical energy is correlated with metabolic energy. Any species or other group that exhibits shape differences should be affected similarly to that which

  17. Chlamydophila spp. infection in horses with recurrent airway obstruction: similarities to human chronic obstructive disease

    Directory of Open Access Journals (Sweden)

    Hotzel Helmut

    2008-01-01

    Full Text Available Abstract Background Recurrent airway obstruction (RAO in horses is a naturally occurring dust-induced disease mainly characterized by bronchiolitis which shows histological and pathophysiological similarities to human chronic obstructive pulmonary disease (COPD. In human COPD previous investigations indicated an association with Chlamydophila psittaci infection. The present study was designed (1 to clarify a possible role of this infectious agent in RAO and (2 to investigate the suitability of this equine disorder as a model for human COPD. Methods Clinico-pathological parameters of a total of 45 horses (25 horses with clinical signs of RAO and 20 clinically healthy controls were compared to histological findings in lung tissue samples and infection by Chlamydiaceae using light microscopy, immunohistochemistry, and PCR. Results Horses with clinical signs of RAO vs. controls revealed more inflammatory changes in histology (p = 0.01, and a higher detection rate of Chlamydia psittaci antigens in all cells (p OmpA sequencing identified Chlamydophila psittaci (n = 9 and Chlamydophila abortus (n = 13 in both groups with no significant differences. Within the group of clinically healthy horses subgroups with no changes (n = 15 and slight inflammation of the small airways (n = 5 were identified. Also in the group of animals with RAO subgroups with slight (n = 16 and severe (n = 9 bronchiolitis could be formed. These four subgroups can be separated in parts by the number of cells positive for Chlamydia psittaci antigens. Conclusion Chlamydophila psittaci or abortus were present in the lung of both clinically healthy horses and those with RAO. Immunohistochemistry revealed acute chlamydial infections with inflammation in RAO horses, whereas in clinically healthy animals mostly persistent chlamydial infection and no inflammatory reactions were seen. Stable dust as the known fundamental abiotic factor in RAO is comparable to smoking in human disease. These

  18. Bioengineered human IAS reconstructs with functional and molecular properties similar to intact IAS

    Science.gov (United States)

    Singh, Jagmohan

    2012-01-01

    Because of its critical importance in rectoanal incontinence, we determined the feasibility to reconstruct internal anal sphincter (IAS) from human IAS smooth muscle cells (SMCs) with functional and molecular attributes similar to the intact sphincter. The reconstructs were developed using SMCs from the circular smooth muscle layer of the human IAS, grown in smooth muscle differentiation media under sterile conditions in Sylgard-coated tissue culture plates with central Sylgard posts. The basal tone in the reconstructs and its changes were recorded following 0 Ca2+, KCl, bethanechol, isoproterenol, protein kinase C (PKC) activator phorbol 12,13-dibutyrate, and Rho kinase (ROCK) and PKC inhibitors Y-27632 and Gö-6850, respectively. Western blot (WB), immunofluorescence (IF), and immunocytochemical (IC) analyses were also performed. The reconstructs developed spontaneous tone (0.68 ± 0.26 mN). Bethanechol (a muscarinic agonist) and K+ depolarization produced contraction, whereas isoproterenol (β-adrenoceptor agonist) and Y-27632 produced a concentration-dependent decrease in the tone. Maximal decrease in basal tone with Y-27632 and Gö-6850 (each 10−5 M) was 80.45 ± 3.29 and 17.76 ± 3.50%, respectively. WB data with the IAS constructs′ SMCs revealed higher levels of RhoA/ROCK, protein kinase C-potentiated inhibitor or inhibitory phosphoprotein for myosin phosphatase (CPI-17), phospho-CPI-17, MYPT1, and 20-kDa myosin light chain vs. rectal smooth muscle. WB, IF, and IC studies of original SMCs and redispersed from the reconstructs for the relative distribution of different signal transduction proteins confirmed the feasibility of reconstruction of IAS with functional properties similar to intact IAS and demonstrated the development of myogenic tone with critical dependence on RhoA/ROCK. We conclude that it is feasible to bioengineer IAS constructs using human IAS SMCs that behave like intact IAS. PMID:22790596

  19. Faces in places: humans and machines make similar face detection errors.

    Directory of Open Access Journals (Sweden)

    Bernard Marius 't Hart

    Full Text Available The human visual system seems to be particularly efficient at detecting faces. This efficiency sometimes comes at the cost of wrongfully seeing faces in arbitrary patterns, including famous examples such as a rock configuration on Mars or a toast's roast patterns. In machine vision, face detection has made considerable progress and has become a standard feature of many digital cameras. The arguably most wide-spread algorithm for such applications ("Viola-Jones" algorithm achieves high detection rates at high computational efficiency. To what extent do the patterns that the algorithm mistakenly classifies as faces also fool humans? We selected three kinds of stimuli from real-life, first-person perspective movies based on the algorithm's output: correct detections ("real faces", false positives ("illusory faces" and correctly rejected locations ("non faces". Observers were shown pairs of these for 20 ms and had to direct their gaze to the location of the face. We found that illusory faces were mistaken for faces more frequently than non faces. In addition, rotation of the real face yielded more errors, while rotation of the illusory face yielded fewer errors. Using colored stimuli increases overall performance, but does not change the pattern of results. When replacing the eye movement by a manual response, however, the preference for illusory faces over non faces disappeared. Taken together, our data show that humans make similar face-detection errors as the Viola-Jones algorithm, when directing their gaze to briefly presented stimuli. In particular, the relative spatial arrangement of oriented filters seems of relevance. This suggests that efficient face detection in humans is likely to be pre-attentive and based on rather simple features as those encoded in the early visual system.

  20. Pain processing in dementia and its relation to neuropathology

    NARCIS (Netherlands)

    Scherder, E.J.A.; Sergeant, J.A.; Swaab, D.F.

    2003-01-01

    Most clinical studies of pain in dementia have focused on assessment procedures that are sensitive to pain in "demented" or "cognitively impaired" elderly patients. The neuropathology of dementia has not played a major part in pain assessment. In this review, the neuropathological effects of

  1. The neuropathology of hereditary congenital facial palsy vs Mobius syndrome.

    NARCIS (Netherlands)

    Verzijl, H.T.F.M.; Zwaag, B. van der; Lammens, M.M.Y.; Donkelaar, H.J. ten; Padberg, G.W.A.M.

    2005-01-01

    OBJECTIVE: To characterize the neuropathology of hereditary congenital facial palsy. METHODS: The authors compared brainstem pathology of three members of one family with autosomal dominant congenital facial palsy to that in three age-matched controls. The neuropathologic findings of the familial

  2. Cunninghamella Biotransformation--Similarities to Human Drug Metabolism and Its Relevance for the Drug Discovery Process.

    Science.gov (United States)

    Piska, Kamil; Żelaszczyk, Dorota; Jamrozik, Marek; Kubowicz-Kwaśny, Paulina; Pękala, Elżbieta

    2016-01-01

    Studies of drug metabolism are one of the most significant issues in the process of drug development, its introduction to the market and also in treatment. Even the most promising molecule may show undesirable metabolic properties that would disqualify it as a potential drug. Therefore, such studies are conducted in the early phases of drug discovery and development process. Cunninghamella is a filamentous fungus known for its catalytic properties, which mimics mammalian drug metabolism. It has been proven that C. elegans carries at least one gene coding for a CYP enzyme closely related to the CYP51 family. The transformation profile of xenobiotics in Cunninghamella spp. spans a number of reactions catalyzed by different mammalian CYP isoforms. This paper presents detailed data on similar biotransformation drug products in humans and Cunninghamella spp. and covers the most important aspects of preparative biosynthesis of metabolites, since this model allows to obtain metabolites in sufficient quantities to conduct the further detailed investigations, as quantification, structure analysis and pharmacological activity and toxicity testing. The metabolic activity of three mostly used Cunninghamella species in obtaining hydroxylated, dealkylated and oxidated metabolites of different drugs confirmed its convergence with human biotransformation. Though it cannot replace the standard methods, it can provide support in the field of biotransformation and identifying metabolic soft spots of new chemicals and in predicting possible metabolic pathways. Another aspect is the biosynthesis of metabolites. In this respect, techniques using Cunninghamella spp. seem to be competitive to the chemical methods currently used.

  3. Human brain mass: similar body composition associations as observed across mammals.

    Science.gov (United States)

    Heymsfield, Steven B; Müller, Manfred J; Bosy-Westphal, Anja; Thomas, Diana; Shen, Wei

    2012-01-01

    A classic association is the link between brain mass and body mass across mammals that has now been shown to derive from fat-free mass (FFM) and not fat mass (FM). This study aimed to establish for the first time the associations between human brain mass and body composition and to compare these relations with those established for liver as a reference organ. Subjects were 112 men and 148 women who had brain and liver mass measured by magnetic resonance imaging with FM and FFM measured by dual-energy X-ray absorptiometry. Brain mass scaled to height (H) with powers of ≤0.6 in men and women; liver mass and FFM both scaled similarly as H(~2) . The fraction of FFM as brain thus scaled inversely to height (P FFM was independent of height. After controlling for age, brain, and liver mass were associated with FFM while liver was additionally associated with FM (all models P ≤ 0.01). After controlling for age and sex, FFM accounted for ~5% of the variance in brain mass while levels were substantially higher for liver mass (~60%). Brain mass was significantly larger (P FFM. As across mammals, human brain mass associates significantly, although weakly, with FFM and not FM; the fraction of FFM as brain relates inversely to height; brain differs in these relations from liver, another small high metabolic rate organ; and the sexual dimorphism in brain mass persists even after adjusting for age and FFM. Copyright © 2012 Wiley Periodicals, Inc.

  4. Canine and human gastrointestinal stromal tumors display similar mutations in c-KIT exon 11

    International Nuclear Information System (INIS)

    Gregory-Bryson, Emmalena; Bartlett, Elizabeth; Kiupel, Matti; Hayes, Schantel; Yuzbasiyan-Gurkan, Vilma

    2010-01-01

    Gastrointestinal stromal tumors (GISTs) are common mesenchymal neoplasms in the gastrointestinal tract of humans and dogs. Little is known about the pathogenesis of these tumors. This study evaluated the role of c-KIT in canine GISTs; specifically, we investigated activating mutations in exons 8, 9, 11, 13, and 17 of c-KIT and exons 12, 14, and 18 of platelet-derived growth factor receptor, alpha polypeptide (PDGFRA), all of which have been implicated in human GISTs. Seventeen canine GISTs all confirmed to be positive for KIT immunostaining were studied. Exons 8, 9, 11, 13 and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA, were amplified from DNA isolated from formalin-fixed paraffin-embedded samples. Of these seventeen cases, six amplicons of exon 11 of c-KIT showed aberrant bands on gel electrophoresis. Sequencing of these amplicons revealed heterozygous in-frame deletions in six cases. The mutations include two different but overlapping six base pair deletions. Exons 8, 9, 13, and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA had no abnormalities detected by electrophoresis and sequencing did not reveal any mutations, other than synonymous single nucleotide polymorphisms (SNPs) found in exon 11 of c-KIT and exons 12 and 14 of PDGFRA. The deletion mutations detected in canine GISTs are similar to those previously found in the juxtamembrane domain of c-KIT in canine cutaneous mast cell tumors in our laboratory as well as to those reported in human GISTs. Interestingly, none of the other c-KIT or PDGFRA exons showed any abnormalities in our cases. This finding underlines the critical importance of c-KIT in the pathophysiology of canine GISTs. The expression of KIT and the identification of these activating mutations in c-KIT implicate KIT in the pathogenesis of these tumors. Our results indicate that mutations in c-KIT may be of prognostic significance and that targeting KIT may be a rational approach to treatment of these malignant tumors. This study further

  5. Visual motion transforms visual space representations similarly throughout the human visual hierarchy.

    Science.gov (United States)

    Harvey, Ben M; Dumoulin, Serge O

    2016-02-15

    Several studies demonstrate that visual stimulus motion affects neural receptive fields and fMRI response amplitudes. Here we unite results of these two approaches and extend them by examining the effects of visual motion on neural position preferences throughout the hierarchy of human visual field maps. We measured population receptive field (pRF) properties using high-field fMRI (7T), characterizing position preferences simultaneously over large regions of the visual cortex. We measured pRFs properties using sine wave gratings in stationary apertures, moving at various speeds in either the direction of pRF measurement or the orthogonal direction. We find direction- and speed-dependent changes in pRF preferred position and size in all visual field maps examined, including V1, V3A, and the MT+ map TO1. These effects on pRF properties increase up the hierarchy of visual field maps. However, both within and between visual field maps the extent of pRF changes was approximately proportional to pRF size. This suggests that visual motion transforms the representation of visual space similarly throughout the visual hierarchy. Visual motion can also produce an illusory displacement of perceived stimulus position. We demonstrate perceptual displacements using the same stimulus configuration. In contrast to effects on pRF properties, perceptual displacements show only weak effects of motion speed, with far larger speed-independent effects. We describe a model where low-level mechanisms could underlie the observed effects on neural position preferences. We conclude that visual motion induces similar transformations of visuo-spatial representations throughout the visual hierarchy, which may arise through low-level mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Similar uptake profiles of microcystin-LR and -RR in an in vitro human intestinal model

    International Nuclear Information System (INIS)

    Zeller, P.; Clement, M.; Fessard, V.

    2011-01-01

    Highlights: → First description of in vitro cellular uptake of MCs into intestinal cells. → OATP 3A1 and OATP 4A1 are expressed in Caco-2 cell membranes. → MC-LR and MC-RR show similar uptake in Caco-2 cells. → MCs are probably excreted from Caco-2 cells by an active mechanism. -- Abstract: Microcystins (MCs) are cyclic hepatotoxins produced by various species of cyanobacteria. Their structure includes two variable amino acids (AA) leading to more than 80 MC variants. In this study, we focused on the most common variant, microcystin-LR (MC-LR), and microcystin-RR (MC-RR), a variant differing by only one AA. Despite their structural similarity, MC-LR elicits higher liver toxicity than MC-RR partly due to a discrepancy in their uptake by hepatic organic anion transporters (OATP 1B1 and 1B3). However, even though ingestion is the major pathway of human exposure to MCs, intestinal absorption of MCs has been poorly addressed. Consequently, we investigated the cellular uptake of the two MC variants in the human intestinal cell line Caco-2 by immunolocalization using an anti-MC antibody. Caco-2 cells were treated for 30 min to 24 h with several concentrations (1-50 μM) of both variants. We first confirmed the localization of OATP 3A1 and 4A1 at the cell membrane of Caco-2 cells. Our study also revealed a rapid uptake of both variants in less than 1 h. The uptake profiles of the two variants did not differ in our immunostaining study neither with respect to concentration nor the time of exposure. Furthermore, we have demonstrated for the first time the nuclear localization of MC-RR and confirmed that of MC-LR. Finally, our results suggest a facilitated uptake and an active excretion of MC-LR and MC-RR in Caco-2 cells. Further investigation on the role of OATP 3A1 and 4A1 in MC uptake should be useful to clarify the mechanism of intestinal absorption of MCs and contribute in risk assessment of cyanotoxin exposure.

  7. Structural and functional similarities between osmotin from Nicotiana tabacum seeds and human adiponectin.

    Science.gov (United States)

    Miele, Marco; Costantini, Susan; Colonna, Giovanni

    2011-02-02

    Osmotin, a plant protein, specifically binds a seven transmembrane domain receptor-like protein to exert its biological activity via a RAS2/cAMP signaling pathway. The receptor protein is encoded in the gene ORE20/PHO36 and the mammalian homolog of PHO36 is a receptor for the human hormone adiponectin (ADIPOR1). Moreover it is known that the osmotin domain I can be overlapped to the β-barrel domain of adiponectin. Therefore, these observations and some already existing structural and biological data open a window on a possible use of the osmotin or of its derivative as adiponectin agonist. We have modelled the three-dimensional structure of the adiponectin trimer (ADIPOQ), and two ADIPOR1 and PHO36 receptors. Moreover, we have also modelled the following complexes: ADIPOQ/ADIPOR1, osmotin/PHO36 and osmotin/ADIPOR1. We have then shown the structural determinants of these interactions and their physico-chemical features and analyzed the related interaction residues involved in the formation of the complexes. The stability of the modelled structures and their complexes was always evaluated and controlled by molecular dynamics. On the basis of these results a 9 residues osmotin peptide was selected and its interaction with ADIPOR1 and PHO36 was modelled and analysed in term of energetic stability by molecular dynamics. To confirm in vivo the molecular modelling data, osmotin has been purified from nicotiana tabacum seeds and its nine residues peptide synthesized. We have used cultured human synovial fibroblasts that respond to adiponectin by increasing the expression of IL-6, TNF-alpha and IL-1beta via ADIPOR1. The biological effect on fibroblasts of osmotin and its peptide derivative has been found similar to that of adiponectin confirming the results found in silico.

  8. Strain-specific viral distribution and neuropathology of feline immunodeficiency virus.

    Science.gov (United States)

    Miller, Craig; Bielefeldt-Ohmann, Helle; MacMillan, Martha; Huitron-Resendiz, Salvador; Henriksen, Steven; Elder, John; VandeWoude, Susan

    2011-10-15

    Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of domestic cats, and is the causative agent of feline AIDS. Similar to human immunodeficiency virus (HIV), the pathogenesis of FIV involves infection of lymphocytes and macrophages, and results in chronic progressive immune system collapse and death. Neuropathologic correlates of FIV infection have not yet been elucidated, and may be relevant to understanding HIV-associated neurologic disease (neuroAIDS). As in HIV, FIV strains have been shown to express differential tendencies towards development of clinical neuroAIDS. To interrogate viral genetic determinants that might contribute to neuropathogenicity, cats were exposed to two well-characterized FIV strains with divergent clinical phenotypes and a chimeric strain as follows: FIV(PPR) (PPR, relatively apathogenic but associated with neurologic manifestations), FIV(C36) (C36, immunopathogenic but without associated neurologic disease), and Pcenv (a chimeric virus consisting of a PPR backbone with substituted C36 env region). A sham inoculum control group was also included. Peripheral nerve conduction velocity, CNS imaging studies, viral loads and hematologic analysis were performed over a 12 month period. At termination of the study (350 days post-inoculation), brain sections were obtained from four anatomic locations known to be involved in human and primate lentiviral neuroAIDS. Histological and immunohistochemical evaluation with seven markers of inflammation revealed that Pcenv infection resulted in mild inflammation of the CNS, microglial activation, neuronal degeneration and apoptosis, while C36 and PPR strains induced minimal neuropathologic changes. Conduction velocity aberrations were noted peripherally in all three groups at 63 weeks post-infection. Pcenv viral load in this study was intermediate to the parental strains (C36 demonstrating the highest viral load and PPR the lowest). These results collectively suggest that (i) 3' C36

  9. Do humans (Homo sapiens) and fish (Pterophyllum scalare) make similar numerosity judgments?

    Science.gov (United States)

    Miletto Petrazzini, Maria Elena; Agrillo, Christian; Izard, Véronique; Bisazza, Angelo

    2016-11-01

    Numerous studies have shown that many animal species can be trained to discriminate between stimuli differing in numerosity. However, in the absence of generalization tests with untrained numerosities, what decision criterion was used by subjects remains unclear: the subjects may succeed by selecting a specific number of items (a criterion over absolute numerosities), or by applying a more general relative numerosity rule, for example, selecting the larger/smaller quantity of items. The latter case may require more powerful representations, supporting judgments of order ("more/less") beyond simple "same/different" judgments, but a relative numerosity rule may also be more adaptive. In previous research, we showed that guppies (Poecilia reticulata) spontaneously prefer relative numerosity rules. To date it is unclear whether this preference is shared by other fish and, more broadly, other species. Here we compared the performance of angelfish (Pterophyllum scalare) with that of human adults (Homo sapiens) in a task in which subjects were initially trained to select arrays containing 10 dots (either in 5 vs. 10 or 10 vs. 20 comparisons). Subsequently they were tested with the previously trained numerosity and a novel numerosity (respectively, 20 or 5). In the absence of explicit instructions, both species spontaneously favored a relative rule, selecting the novel numerosity. These similarities demonstrate that, beyond shared representations for numerical quantities, vertebrate species may also share a system for taking decisions about quantities. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  10. Circulating Human Eosinophils Share a Similar Transcriptional Profile in Asthma and Other Hypereosinophilic Disorders.

    Science.gov (United States)

    Barnig, Cindy; Alsaleh, Ghada; Jung, Nicolas; Dembélé, Doulaye; Paul, Nicodème; Poirot, Anh; Uring-Lambert, Béatrice; Georgel, Philippe; de Blay, Fréderic; Bahram, Seiamak

    2015-01-01

    Eosinophils are leukocytes that are released into the peripheral blood in a phenotypically mature state and are capable of being recruited into tissues in response to appropriate stimuli. Eosinophils, traditionally considered cytotoxic effector cells, are leukocytes recruited into the airways of asthma patients where they are believed to contribute to the development of many features of the disease. This perception, however, has been challenged by recent findings suggesting that eosinophils have also immunomodulatory functions and may be involved in tissue homeostasis and wound healing. Here we describe a transcriptome-based approach-in a limited number of patients and controls-to investigate the activation state of circulating human eosinophils isolated by flow cytometry. We provide an overview of the global expression pattern in eosinophils in various relevant conditions, e.g., eosinophilic asthma, hypereosinophilic dermatological diseases, parasitosis and pulmonary aspergillosis. Compared to healthy subjects, circulating eosinophils isolated from asthma patients differed in their gene expression profile which is marked by downregulation of transcripts involved in antigen presentation, pathogen recognition and mucosal innate immunity, whereas up-regulated genes were involved in response to non-specific stimulation, wounding and maintenance of homeostasis. Eosinophils from other hypereosinophilic disorders displayed a very similar transcriptional profile. Taken together, these observations seem to indicate that eosinophils exhibit non-specific immunomodulatory functions important for tissue repair and homeostasis and suggest new roles for these cells in asthma immunobiology.

  11. Similar metabolic responses in pigs and humans to breads with different contents and compositions of dietary fibers: a metabolomics study

    DEFF Research Database (Denmark)

    Nielsen, Kirstine Lykke; Hartvigsen, Merete; Hedemann, Mette Skou

    2014-01-01

    Background: In nutritional studies, pigs are often used as models for humans because of nutritional and physiologic similarities. However, evidence supporting similar metabolic responses to nutritional interventions is lacking. Objective: The objective was to establish whether pigs and humans...... respond similarly to a nutritional intervention. Using metabolomics, we compared the acute metabolic response to 4 test breads between conventional pigs (growing) and adult human subjects (with the metabolic syndrome). Design: Six catheterized pigs and 15 human subjects were tested in a randomized...... different basal metabolome concentrations in the plasma of pigs and humans. Humans had higher contents of phosphatidylcholines, oleic acid, and carnitine in plasma, possibly reflecting a higher intake of meats and fats. In pigs, betaine, choline, creatinine, tryptophan, and phenylalanine were higher...

  12. A study on the quantitative model of human response time using the amount and the similarity of information

    International Nuclear Information System (INIS)

    Lee, Sung Jin

    2006-02-01

    The mental capacity to retain or recall information, or memory is related to human performance during processing of information. Although a large number of studies have been carried out on human performance, little is known about the similarity effect. The purpose of this study was to propose and validate a quantitative and predictive model on human response time in the user interface with the basic concepts of information amount, similarity and degree of practice. It was difficult to explain human performance by only similarity or information amount. There were two difficulties: constructing a quantitative model on human response time and validating the proposed model by experimental work. A quantitative model based on the Hick's law, the law of practice and similarity theory was developed. The model was validated under various experimental conditions by measuring the participants' response time in the environment of a computer-based display. Human performance was improved by degree of similarity and practice in the user interface. Also we found the age-related human performance which was degraded as he or she was more elder. The proposed model may be useful for training operators who will handle some interfaces and predicting human performance by changing system design

  13. Warping similarity space in category learning by human subjects: the role of task difficulty

    OpenAIRE

    Pevtzow, Rachel; Harnad, Stevan

    1997-01-01

    In innate Categorical Perception (CP) (e.g., colour perception), similarity space is "warped," with regions of increased within-category similarity (compression) and regions of reduced between-category similarity (separation) enh ancing the category boundaries and making categorisation reliable and all-or-none rather than graded. We show that category learning can likewise warp similarity space, resolving uncertainty near category boundaries. Two Hard and two Easy texture learning tasks were ...

  14. The Neuropathology of Chronic Traumatic Encephalopathy

    Science.gov (United States)

    McKee, Ann C.; Stein, Thor D.; Kiernan, Patrick T.; Alvarez, Victor E.

    2015-01-01

    Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE). Most instances of CTE occur in association with the play of sports, but CTE has also been reported in association with blast injuries and other neurotrauma. Symptoms of CTE include behavioral and mood changes, memory loss, cognitive impairment and dementia. Like many other neurodegenerative diseases, CTE is diagnosed with certainty only by neuropathological examination of brain tissue. CTE is a tauopathy characterized by the deposition of hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles, astrocytic tangles and neurites in striking clusters around small blood vessels of the cortex, typically at the sulcal depths. Severely affected cases show p-tau pathology throughout the brain. Abnormalities in phosphorylated 43 kDa TAR DNA-binding protein are found in most cases of CTE; beta-amyloid is identified in 43%, associated with age. Given the importance of sports participation and physical exercise to physical and psychological health as well as disease resilience, it is critical to identify the genetic risk factors for CTE as well as to understand how other variables, such as stress, age at exposure, gender, substance abuse and other exposures, contribute to the development of CTE. PMID:25904048

  15. How glitter relates to gold : Similarity-dependent reward prediction errors in the human striatum

    NARCIS (Netherlands)

    Kahnt, T.; Park, S.Q.; Burke, C.; Tobler, P.N.

    2012-01-01

    Optimal choices benefit from previous learning. However, it is not clear how previously learned stimuli influence behavior to novel but similar stimuli. One possibility is to generalize based on the similarity between learned and current stimuli. Here, we use neuroscientific methods and a novel

  16. Increased aggression during human group contests when competitive ability is more similar

    NARCIS (Netherlands)

    Stulp, Gert; Kordsmeyer, Tobias; Buunk, Abraham P.; Verhulst, Simon

    2012-01-01

    Theoretical analyses and empirical studies have revealed that conflict escalation is more likely when individuals are more similar in resource-holding potential (RHP). Conflicts can also occur between groups, but it is unknown whether conflicts also escalate more when groups are more similar in RHP.

  17. Cell Type-Specific Contributions to the TSC Neuropathology

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-16-1-0415 TITLE: Cell Type-Specific Contributions to the TSC Neuropathology PRINCIPAL INVESTIGATOR: Gabriella D’Arcangelo...AND SUBTITLE Cell Type-Specific Contributions to the TSC Neuropathology 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0415 5c. PROGRAM...how heterozygous and homozygous Tsc2 mutations affect the development of mutant excitatory neurons as well as other surrounding brain cells , in vivo

  18. Overexpression of mutant ataxin-3 in mouse cerebellum induces ataxia and cerebellar neuropathology.

    Science.gov (United States)

    Nóbrega, Clévio; Nascimento-Ferreira, Isabel; Onofre, Isabel; Albuquerque, David; Conceição, Mariana; Déglon, Nicole; de Almeida, Luís Pereira

    2013-08-01

    Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is a fatal, dominant neurodegenerative disorder caused by the polyglutamine-expanded protein ataxin-3. Clinical manifestations include cerebellar ataxia and pyramidal signs culminating in severe neuronal degeneration. Currently, there is no therapy able to modify disease progression. In the present study, we aimed at investigating one of the most severely affected brain regions in the disorder--the cerebellum--and the behavioral defects associated with the neuropathology in this region. For this purpose, we injected lentiviral vectors encoding full-length human mutant ataxin-3 in the mouse cerebellum of 3-week-old C57/BL6 mice. We show that circumscribed expression of human mutant ataxin-3 in the cerebellum mediates within a short time frame--6 weeks, the development of a behavioral phenotype including reduced motor coordination, wide-based ataxic gait, and hyperactivity. Furthermore, the expression of mutant ataxin-3 resulted in the accumulation of intranuclear inclusions, neuropathological abnormalities, and neuronal death. These data show that lentiviral-based expression of mutant ataxin-3 in the mouse cerebellum induces localized neuropathology, which is sufficient to generate a behavioral ataxic phenotype. Moreover, this approach provides a physiologically relevant, cost-effective and time-effective animal model to gain further insights into the pathogenesis of MJD and for the evaluation of experimental therapeutics of MJD.

  19. Dog Experts' Brains Distinguish Socially Relevant Body Postures Similarly in Dogs and Humans

    OpenAIRE

    Kujala, Miiamaaria; Kujala, Jan; Carlson, Synnove; Hari, Riitta

    2012-01-01

    We read conspecifics' social cues effortlessly, but little is known about our abilities to understand social gestures of other species. To investigate the neural underpinnings of such skills, we used functional magnetic resonance imaging to study the brain activity of experts and non-experts of dog behavior while they observed humans or dogs either interacting with, or facing away from a conspecific. The posterior superior temporal sulcus (pSTS) of both subject groups dissociated humans facin...

  20. Autism spectrum disorders and neuropathology of the cerebellum.

    Science.gov (United States)

    Hampson, David R; Blatt, Gene J

    2015-01-01

    The cerebellum contains the largest number of neurons and synapses of any structure in the central nervous system. The concept that the cerebellum is solely involved in fine motor function has become outdated; substantial evidence has accumulated linking the cerebellum with higher cognitive functions including language. Cerebellar deficits have been implicated in autism for more than two decades. The computational power of the cerebellum is essential for many, if not most of the processes that are perturbed in autism including language and communication, social interactions, stereotyped behavior, motor activity and motor coordination, and higher cognitive functions. The link between autism and cerebellar dysfunction should not be surprising to those who study its cellular, physiological, and functional properties. Postmortem studies have revealed neuropathological abnormalities in cerebellar cellular architecture while studies on mouse lines with cell loss or mutations in single genes restricted to cerebellar Purkinje cells have also strongly implicated this brain structure in contributing to the autistic phenotype. This connection has been further substantiated by studies investigating brain damage in humans restricted to the cerebellum. In this review, we summarize advances in research on idiopathic autism and three genetic forms of autism that highlight the key roles that the cerebellum plays in this spectrum of neurodevelopmental disorders.

  1. Autism Spectrum Disorders and Neuropathology of the Cerebellum

    Directory of Open Access Journals (Sweden)

    David R Hampson

    2015-11-01

    Full Text Available The cerebellum contains the largest number of neurons and synapses of any structure in the central nervous system. The concept that the cerebellum is solely involved in fine motor function has become outdated; substantial evidence has accumulated linking the cerebellum with higher cognitive functions including language. Cerebellar deficits have been implicated in autism for more than two decades. The computational power of the cerebellum is essential for many, if not most of the processes that are perturbed in autism including language and communication, social interactions, stereotyped behavior, motor activity and motor coordination, and higher cognitive functions. The link between autism and cerebellar dysfunction should not be surprising to those who study its cellular, physiological, and functional properties. Postmortem studies have revealed neuropathological abnormalities in cerebellar cellular architecture while studies on mouse lines with cell loss or mutations in single genes restricted to cerebellar Purkinje cells have also strongly implicated this brain structure in contributing to the autistic phenotype. This connection has been further substantiated by studies investigating brain damage in humans restricted to the cerebellum. In this review, we summarize advances in research on idiopathic autism and three genetic forms of autism that highlight the key roles that the cerebellum plays in this spectrum of neurodevelopmental disorders.

  2. MicroRNA Implications across Neurodevelopment and Neuropathology

    Directory of Open Access Journals (Sweden)

    Sabata Martino

    2009-01-01

    Full Text Available MicroRNAs (miRNAs have rapidly emerged as biologically important mediators of posttranscriptional and epigenetic regulation in both plants and animals. miRNAs function through a variety of mechanisms including mRNA degradation and translational repression; additionally, miRNAs may guide gene expression by serving as transcription factors. miRNAs are highly expressed in human brain. Tissue and cell type-specific enrichments of certain miRNAs within the nervous system argue for a biological significance during neurodevelopmental stages. On the other hand, a large number of studies have reported links between alterations of miRNA homeostasis and pathologic conditions such as cancer, heart diseases, and neurodegeneration. Thus, profiles of distinct or aberrant miRNA signatures have most recently surged as one of the most fascinating interests in current biology. Here, the most recent insights into the involvement of miRNAs in the biology of the nervous system and the occurrence of neuropathological disorders are reviewed and discussed.

  3. Recognition of HIV-1 peptides by host CTL is related to HIV-1 similarity to human proteins.

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    Morgane Rolland

    Full Text Available BACKGROUND: While human immunodeficiency virus type 1 (HIV-1-specific cytotoxic T lymphocytes preferentially target specific regions of the viral proteome, HIV-1 features that contribute to immune recognition are not well understood. One hypothesis is that similarities between HIV and human proteins influence the host immune response, i.e., resemblance between viral and host peptides could preclude reactivity against certain HIV epitopes. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the extent of similarity between HIV-1 and the human proteome. Proteins from the HIV-1 B consensus sequence from 2001 were dissected into overlapping k-mers, which were then probed against a non-redundant database of the human proteome in order to identify segments of high similarity. We tested the relationship between HIV-1 similarity to host encoded peptides and immune recognition in HIV-infected individuals, and found that HIV immunogenicity could be partially modulated by the sequence similarity to the host proteome. ELISpot responses to peptides spanning the entire viral proteome evaluated in 314 individuals showed a trend indicating an inverse relationship between the similarity to the host proteome and the frequency of recognition. In addition, analysis of responses by a group of 30 HIV-infected individuals against 944 overlapping peptides representing a broad range of individual HIV-1B Nef variants, affirmed that the degree of similarity to the host was significantly lower for peptides with reactive epitopes than for those that were not recognized. CONCLUSIONS/SIGNIFICANCE: Our results suggest that antigenic motifs that are scarcely represented in human proteins might represent more immunogenic CTL targets not selected against in the host. This observation could provide guidance in the design of more effective HIV immunogens, as sequences devoid of host-like features might afford superior immune reactivity.

  4. Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

    KAUST Repository

    Hoehndorf, Robert; Schofield, Paul N.; Gkoutos, Georgios V.

    2015-01-01

    of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs

  5. Evidence for two numerical systems that are similar in humans and guppies.

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    Christian Agrillo

    Full Text Available BACKGROUND: Humans and non-human animals share an approximate non-verbal system for representing and comparing numerosities that has no upper limit and for which accuracy is dependent on the numerical ratio. Current evidence indicates that the mechanism for keeping track of individual objects can also be used for numerical purposes; if so, its accuracy will be independent of numerical ratio, but its capacity is limited to the number of items that can be tracked, about four. There is, however, growing controversy as to whether two separate number systems are present in other vertebrate species. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we compared the ability of undergraduate students and guppies to discriminate the same numerical ratios, both within and beyond the small number range. In both students and fish the performance was ratio-independent for the numbers 1-4, while it steadily increased with numerical distance when larger numbers were presented. CONCLUSIONS/SIGNIFICANCE: Our results suggest that two distinct systems underlie quantity discrimination in both humans and fish, implying that the building blocks of uniquely human mathematical abilities may be evolutionarily ancient, dating back to before the divergence of bony fish and tetrapod lineages.

  6. Defining the molecular pathologies in cloaca malformation: similarities between mouse and human

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    Laura A. Runck

    2014-04-01

    Full Text Available Anorectal malformations are congenital anomalies that form a spectrum of disorders, from the most benign type with excellent functional prognosis, to very complex, such as cloaca malformation in females in which the rectum, vagina and urethra fail to develop separately and instead drain via a single common channel into the perineum. The severity of this phenotype suggests that the defect occurs in the early stages of embryonic development of the organs derived from the cloaca. Owing to the inability to directly investigate human embryonic cloaca development, current research has relied on the use of mouse models of anorectal malformations. However, even studies of mouse embryos lack analysis of the earliest stages of cloaca patterning and morphogenesis. Here we compared human and mouse cloaca development and retrospectively identified that early mis-patterning of the embryonic cloaca might underlie the most severe forms of anorectal malformation in humans. In mouse, we identified that defective sonic hedgehog (Shh signaling results in early dorsal-ventral epithelial abnormalities prior to the reported defects in septation. This is manifested by the absence of Sox2 and aberrant expression of keratins in the embryonic cloaca of Shh knockout mice. Shh knockout embryos additionally develop a hypervascular stroma, which is defective in BMP signaling. These epithelial and stromal defects persist later, creating an indeterminate epithelium with molecular alterations in the common channel. We then used these animals to perform a broad comparison with patients with mild-to-severe forms of anorectal malformations including cloaca malformation. We found striking parallels with the Shh mouse model, including nearly identical defective molecular identity of the epithelium and surrounding stroma. Our work strongly suggests that early embryonic cloacal epithelial differentiation defects might be the underlying cause of severe forms of anorectal malformations

  7. Organization and evolution of Drosophila terminin: similarities and differences between Drosophila and human telomeres

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    Grazia Daniela Raffa

    2013-05-01

    Full Text Available Drosophila lacks telomerase and fly telomeres are elongated by occasional transposition of three specialized retroelements. Drosophila telomeres do not terminate with GC-rich repeats and are assembled independently of the sequence of chromosome ends. Recent work has shown that Drosophila telomeres are capped by the terminin complex, which includes the fast-evolving proteins HOAP, HipHop, Moi and Ver. These proteins are not conserves outside Drosophilidae and localize and function exclusively at telomeres, protecting them from fusion events. Other proteins required to prevent end-to-end fusion in flies include HP1, Eff/UbcD1, ATM, the components of the Mre11-Rad50-Nbs (MRN complex, and the Woc transcription factor. These proteins do not share the terminin properties; they are evolutionarily conserved non-fast-evolving proteins that do not accumulate only telomeres and do not serve telomere-specific functions. We propose that following telomerase loss, Drosophila rapidly evolved terminin to bind chromosome ends in a sequence-independent manner. This hypothesis suggests that terminin is the functional analog of the shelterin complex that protects human telomeres. The non-terminin proteins are instead likely to correspond to ancestral telomere-associated proteins that did not evolve as rapidly as terminin because of the functional constraints imposed by their involvement in diverse cellular processes. Thus, it appears that the main difference between Drosophila and human telomeres is in the protective complexes that specifically associate with the DNA termini. We believe that Drosophila telomeres offer excellent opportunities for investigations on human telomere biology. The identification of additional Drosophila genes encoding non-terminin proteins involved in telomere protection might lead to the discovery of novel components of human telomeres.

  8. The G protein-coupled receptor subset of the dog genome is more similar to that in humans than rodents.

    Science.gov (United States)

    Haitina, Tatjana; Fredriksson, Robert; Foord, Steven M; Schiöth, Helgi B; Gloriam, David E

    2009-01-15

    The dog is an important model organism and it is considered to be closer to humans than rodents regarding metabolism and responses to drugs. The close relationship between humans and dogs over many centuries has lead to the diversity of the canine species, important genetic discoveries and an appreciation of the effects of old age in another species. The superfamily of G protein-coupled receptors (GPCRs) is one of the largest gene families in most mammals and the most exploited in terms of drug discovery. An accurate comparison of the GPCR repertoires in dog and human is valuable for the prediction of functional similarities and differences between the species. We searched the dog genome for non-olfactory GPCRs and obtained 353 full-length GPCR gene sequences, 18 incomplete sequences and 13 pseudogenes. We established relationships between human, dog, rat and mouse GPCRs resolving orthologous pairs and species-specific duplicates. We found that 12 dog GPCR genes are missing in humans while 24 human GPCR genes are not part of the dog GPCR repertoire. There is a higher number of orthologous pairs between dog and human that are conserved as compared with either mouse or rat. In almost all cases the differences observed between the dog and human genomes coincide with other variations in the rodent species. Several GPCR gene expansions characteristic for rodents are not found in dog. The repertoire of dog non-olfactory GPCRs is more similar to the repertoire in humans as compared with the one in rodents. The comparison of the dog, human and rodent repertoires revealed several examples of species-specific gene duplications and deletions. This information is useful in the selection of model organisms for pharmacological experiments.

  9. The G protein-coupled receptor subset of the dog genome is more similar to that in humans than rodents

    Directory of Open Access Journals (Sweden)

    Schiöth Helgi B

    2009-01-01

    Full Text Available Abstract Background The dog is an important model organism and it is considered to be closer to humans than rodents regarding metabolism and responses to drugs. The close relationship between humans and dogs over many centuries has lead to the diversity of the canine species, important genetic discoveries and an appreciation of the effects of old age in another species. The superfamily of G protein-coupled receptors (GPCRs is one of the largest gene families in most mammals and the most exploited in terms of drug discovery. An accurate comparison of the GPCR repertoires in dog and human is valuable for the prediction of functional similarities and differences between the species. Results We searched the dog genome for non-olfactory GPCRs and obtained 353 full-length GPCR gene sequences, 18 incomplete sequences and 13 pseudogenes. We established relationships between human, dog, rat and mouse GPCRs resolving orthologous pairs and species-specific duplicates. We found that 12 dog GPCR genes are missing in humans while 24 human GPCR genes are not part of the dog GPCR repertoire. There is a higher number of orthologous pairs between dog and human that are conserved as compared with either mouse or rat. In almost all cases the differences observed between the dog and human genomes coincide with other variations in the rodent species. Several GPCR gene expansions characteristic for rodents are not found in dog. Conclusion The repertoire of dog non-olfactory GPCRs is more similar to the repertoire in humans as compared with the one in rodents. The comparison of the dog, human and rodent repertoires revealed several examples of species-specific gene duplications and deletions. This information is useful in the selection of model organisms for pharmacological experiments.

  10. More similar than you think: Frog metamorphosis as a model of human perinatal endocrinology.

    Science.gov (United States)

    Buchholz, Daniel R

    2015-12-15

    Hormonal control of development during the human perinatal period is critically important and complex with multiple hormones regulating fetal growth, brain development, and organ maturation in preparation for birth. Genetic and environmental perturbations of such hormonal control may cause irreversible morphological and physiological impairments and may also predispose individuals to diseases of adulthood, including diabetes and cardiovascular disease. Endocrine and molecular mechanisms that regulate perinatal development and that underlie the connections between early life events and adult diseases are not well elucidated. Such mechanisms are difficult to study in uterus-enclosed mammalian embryos because of confounding maternal effects. To elucidate mechanisms of developmental endocrinology in the perinatal period, Xenopus laevis the African clawed frog is a valuable vertebrate model. Frogs and humans have identical hormones which peak at birth and metamorphosis, have conserved hormone receptors and mechanisms of gene regulation, and have comparable roles for hormones in many target organs. Study of molecular and endocrine mechanisms of hormone-dependent development in frogs is advantageous because an extended free-living larval period followed by metamorphosis (1) is independent of maternal endocrine influence, (2) exhibits dramatic yet conserved developmental effects induced by thyroid and glucocorticoid hormones, and (3) begins at a developmental stage with naturally undetectable hormone levels, thereby facilitating endocrine manipulation and interpretation of results. This review highlights the utility of frog metamorphosis to elucidate molecular and endocrine actions, hormone interactions, and endocrine disruption, especially with respect to thyroid hormone. Knowledge from the frog model is expected to provide fundamental insights to aid medical understanding of endocrine disease, stress, and endocrine disruption affecting the perinatal period in humans

  11. Functional similarities between the dictyostelium protein AprA and the human protein dipeptidyl-peptidase IV.

    Science.gov (United States)

    Herlihy, Sarah E; Tang, Yu; Phillips, Jonathan E; Gomer, Richard H

    2017-03-01

    Autocrine proliferation repressor protein A (AprA) is a protein secreted by Dictyostelium discoideum cells. Although there is very little sequence similarity between AprA and any human protein, AprA has a predicted structural similarity to the human protein dipeptidyl peptidase IV (DPPIV). AprA is a chemorepellent for Dictyostelium cells, and DPPIV is a chemorepellent for neutrophils. This led us to investigate if AprA and DPPIV have additional functional similarities. We find that like AprA, DPPIV is a chemorepellent for, and inhibits the proliferation of, D. discoideum cells, and that AprA binds some DPPIV binding partners such as fibronectin. Conversely, rAprA has DPPIV-like protease activity. These results indicate a functional similarity between two eukaryotic chemorepellent proteins with very little sequence similarity, and emphasize the usefulness of using a predicted protein structure to search a protein structure database, in addition to searching for proteins with similar sequences. © 2016 The Protein Society.

  12. Functional similarities between the dictyostelium protein AprA and the human protein dipeptidyl‐peptidase IV

    Science.gov (United States)

    Herlihy, Sarah E.; Tang, Yu; Phillips, Jonathan E.

    2017-01-01

    Abstract Autocrine proliferation repressor protein A (AprA) is a protein secreted by Dictyostelium discoideum cells. Although there is very little sequence similarity between AprA and any human protein, AprA has a predicted structural similarity to the human protein dipeptidyl peptidase IV (DPPIV). AprA is a chemorepellent for Dictyostelium cells, and DPPIV is a chemorepellent for neutrophils. This led us to investigate if AprA and DPPIV have additional functional similarities. We find that like AprA, DPPIV is a chemorepellent for, and inhibits the proliferation of, D. discoideum cells, and that AprA binds some DPPIV binding partners such as fibronectin. Conversely, rAprA has DPPIV‐like protease activity. These results indicate a functional similarity between two eukaryotic chemorepellent proteins with very little sequence similarity, and emphasize the usefulness of using a predicted protein structure to search a protein structure database, in addition to searching for proteins with similar sequences. PMID:28028841

  13. Type 2 diabetes and obesity induce similar transcriptional reprogramming in human myocytes

    DEFF Research Database (Denmark)

    Väremo, Leif; Henriksen, Tora Ida; Scheele, Camilla

    2017-01-01

    BACKGROUND: Skeletal muscle is one of the primary tissues involved in the development of type 2 diabetes (T2D). The close association between obesity and T2D makes it difficult to isolate specific effects attributed to the disease alone. Therefore, here we set out to identify and characterize...... in sphingolipid metabolism was transcriptionally regulated. CONCLUSIONS: Our findings identify inherent characteristics in myocytes, as a memory of the in vivo phenotype, without the influence from a diabetic or obese extracellular environment, highlighting their importance in the development of T2D....... intrinsic properties of myocytes, associated independently with T2D or obesity. METHODS: We generated and analyzed RNA-seq data from primary differentiated myotubes from 24 human subjects, using a factorial design (healthy/T2D and non-obese/obese), to determine the influence of each specific factor...

  14. Resistance to Alzheimer Disease Neuropathologic Changes and Apparent Cognitive Resilience in the Nun and Honolulu-Asia Aging Studies.

    Science.gov (United States)

    Latimer, Caitlin S; Keene, C Dirk; Flanagan, Margaret E; Hemmy, Laura S; Lim, Kelvin O; White, Lon R; Montine, Kathleen S; Montine, Thomas J

    2017-06-01

    Two population-based studies key to advancing knowledge of brain aging are the Honolulu-Asia Aging Study (HAAS) and the Nun Study. Harmonization of their neuropathologic data allows cross comparison, with findings common to both studies likely generalizable, while distinct observations may point to aging brain changes that are dependent on sex, ethnicity, environment, or lifestyle factors. Here, we expanded the neuropathologic evaluation of these 2 studies using revised NIA-Alzheimer's Association guidelines and compared directly the neuropathologic features of resistance and apparent cognitive resilience. There were significant differences in prevalence of Alzheimer disease neuropathologic change, small vessel vascular brain injury, and Lewy body disease between these 2 studies, suggesting that sex, ethnicity, and lifestyle factors may significantly influence resistance to developing brain injury with age. In contrast, hippocampal sclerosis prevalence was very similar, but skewed to poorer cognitive performance, suggesting that hippocampal sclerosis could act sequentially with other diseases to impair cognitive function. Strikingly, despite these observed differences, the proportion of individuals resistant to all 4 diseases of brain or displaying apparent cognitive resilience was virtually identical between HAAS and Nun Study participants. Future in vivo validation of these results awaits comprehensive biomarkers of these 4 brain diseases. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  15. Ascorbic acid glycation of lens proteins produces UVA sensitizers similar to those in human lens

    International Nuclear Information System (INIS)

    Ortwerth, B.J.; Linetsky, Mikhail; Olesen, P.R.

    1995-01-01

    Soluble calf lens proteins were extensively glycated during a 4 week incubation with ascorbic acid in the presence of oxygen. Amino acids analysis of the dialyzed proteins removed at weekly intervals showed an increasing loss of lysine, arginine and histidine, consistent with the extensive protein cross-linking observed. Irradiation of the dialyzed samples with UVA light (1.0 kJ/cm 2 total illumination through a 338 nm cutoff filter) caused an increasing loss of tryptophan, an additional loss of histidine and the production of micromolar concentrations of hydrogen peroxide. No alteration in amino acid content and no photolytic effects were seen in proteins incubated without ascorbic acid in proteins incubated with glucose for 4 weeks. The rate of hydrogen peroxide formation was linear with each glycated sample with a maximum production of 25 nmol/mg protein illuminated. The possibility that the sensitizer activity was due to an ascorbate-induced oxidation of tryptophan was eliminated by the presence of a heavy metal ion chelator during the incubation and by showing equivalent effects with ascorbate-incubated ribonuclease A, which is devoid of tryptophan. The ascorbate-incubated samples displayed increasing absorbance at wavelengths above 300 nm and increasing fluorescence (340/430) as glycation proceeded. The spectra of the 4 week glycated proteins were identical to those obtained with a solubilized water-insoluble fraction from human lens, which is known to have UVA sensitizer activity. (Author)

  16. The effects of gravity on human walking: a new test of the dynamic similarity hypothesis using a predictive model.

    Science.gov (United States)

    Raichlen, David A

    2008-09-01

    The dynamic similarity hypothesis (DSH) suggests that differences in animal locomotor biomechanics are due mostly to differences in size. According to the DSH, when the ratios of inertial to gravitational forces are equal between two animals that differ in size [e.g. at equal Froude numbers, where Froude = velocity2/(gravity x hip height)], their movements can be made similar by multiplying all time durations by one constant, all forces by a second constant and all linear distances by a third constant. The DSH has been generally supported by numerous comparative studies showing that as inertial forces differ (i.e. differences in the centripetal force acting on the animal due to variation in hip heights), animals walk with dynamic similarity. However, humans walking in simulated reduced gravity do not walk with dynamically similar kinematics. The simulated gravity experiments did not completely account for the effects of gravity on all body segments, and the importance of gravity in the DSH requires further examination. This study uses a kinematic model to predict the effects of gravity on human locomotion, taking into account both the effects of gravitational forces on the upper body and on the limbs. Results show that dynamic similarity is maintained in altered gravitational environments. Thus, the DSH does account for differences in the inertial forces governing locomotion (e.g. differences in hip height) as well as differences in the gravitational forces governing locomotion.

  17. Ischemic perinatal brain damage. Neuropathologic and CT correlations

    Energy Technology Data Exchange (ETDEWEB)

    Crisi, G; Mauri, C; Canossi, G; Della Giustina, E

    1986-01-01

    The term ''hypoxic-ischemic encephalopathy'' covers a large part of neonatal neuropathology including the various forms of intracerebral haemorrhage. In the present work the term is confined to ischemic brain edema and actual infarction, be it diffuse or focal. Eighteen newborns with CT evidence of ischemic brain lesions and infarctual necrosis were selected. Emphasis is placed on current data on neuropathology of ischemic brain edema and its CT appearance. Particular entities such as periventricular leukomalacia and multicystic encephalopathy are discussed. Relationship between CT and temporal profile of cerebral damage is emphasized in order to predict the structural sequelae and the longterm prognosis. 31 refs.

  18. Neuropathological mechanisms of seizures in autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Richard Eugene Frye

    2016-05-01

    Full Text Available This manuscript reviews biological abnormalities shared by autism spectrum disorder (ASD and epilepsy. Two neuropathological findings are shared by ASD and epilepsy: abnormalities in minicolumn architecture and -aminobutyric acid (GABA. The peripheral neuropil, which is the region that contains the inhibition circuits of the minicolumns, has been found to be decreased in the post-mortem ASD brain. ASD and epilepsy are associated with inhibitory GABA neurotransmission abnormalities including reduced GABAA and GABAB subunit expression. These abnormalities can elevate the excitation-to-inhibition balance, resulting in hyperexcitablity of the cortex and, in turn, increases the risk of seizures. Medical abnormalities associated with both epilepsy and ASD are discussed. These include specific genetic syndromes, specific metabolic disorders including disorders of energy metabolism and GABA and glutamate neurotransmission, mineral and vitamin deficiencies, heavy metal exposures and immune dysfunction. Many of these medical abnormalities can result in an elevation of the excitatory-inhibitory balance. Fragile X is linked to dysfunction of the mGluR5 receptor and Fragile X, Angelman and Rett syndromes are linked to a reduction in GABAA receptor expression. Defects in energy metabolism can reduce GABA interneuron function. Both pyridoxine dependent seizures and succinic semialdehyde dehydrogenase deficiency cause GABA deficiencies while urea cycle defects and phenylketonuria cause abnormalities in glutamate neurotransmission. Mineral deficiencies can cause glutamate and GABA neurotransmission abnormalities and heavy metals can cause mitochondrial dysfunction which disrupts GABA metabolism. Thus, both ASD and epilepsy are associated with similar abnormalities that may alter the excitatory-to-inhibitory balance of the cortex. These parallels may explain the high prevalence of epilepsy in ASD and the elevated prevalence of ASD features in individuals with

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

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    Jason A. Koutcher

    2002-01-01

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

  20. Autopsy consent, brain collection, and standardized neuropathologic assessment of ADNI participants: the essential role of the neuropathology core.

    Science.gov (United States)

    Cairns, Nigel J; Taylor-Reinwald, Lisa; Morris, John C

    2010-05-01

    Our objectives are to facilitate autopsy consent, brain collection, and perform standardized neuropathologic assessments of all Alzheimer's Disease Neuroimaging Initiative (ADNI) participants who come to autopsy at the 58 ADNI sites in the USA and Canada. Building on the expertise and resources of the existing Alzheimer's Disease Research Center (ADRC) at Washington University School of Medicine, St. Louis, MO, a Neuropathology Core (NPC) to serve ADNI was established with one new highly motivated research coordinator. The ADNI-NPC coordinator provides training materials and protocols to assist clinicians at ADNI sites in obtaining voluntary consent for brain autopsy in ADNI participants. Secondly, the ADNI-NPC maintains a central laboratory to provide uniform neuropathologic assessments using the operational criteria for the classification of AD and other pathologies defined by the National Alzheimer Coordinating Center (NACC). Thirdly, the ADNI-NPC maintains a state-of-the-art brain bank of ADNI-derived brain tissue to promote biomarker and multi-disciplinary clinicopathologic studies. During the initial year of funding of the ADNI Neuropathology Core, there was notable improvement in the autopsy rate to 44.4%. In the most recent year of funding (September 1(st), 2008 to August 31(st) 2009), our autopsy rate improved to 71.5%. Although the overall numbers to date are small, these data demonstrate that the Neuropathology Core has established the administrative organization with the participating sites to harvest brains from ADNI participants who come to autopsy. Within two years of operation, the Neuropathology Core has: (1) implemented a protocol to solicit permission for brain autopsy in ADNI participants at all 58 sites who die and (2) to send appropriate brain tissue from the decedents to the Neuropathology Core for a standardized, uniform, and state-of-the-art neuropathologic assessment. The benefit to ADNI of the implementation of the NPC is very clear

  1. NCR1 Expression Identifies Canine Natural Killer Cell Subsets with Phenotypic Similarity to Human Natural Killer Cells

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    Jennifer Ann Foltz

    2016-11-01

    Full Text Available Canines spontaneously develop many cancers similar to humans - including osteosarcoma, leukemia, and lymphoma - offering the opportunity to study immune therapies in a genetically heterogeneous and immunocompetent environment. However, a lack of antibodies recognizing canine NK cell markers has resulted in suboptimal characterization and unknown purity of NK cell products, hindering the development of canine models of NK cell adoptive immunotherapy. To this end, we generated a novel antibody to canine NCR1 (NKp46, the putative species-wide marker of NK cells, enabling purification of NK cells for further characterization. We demonstrate that CD3-/NKp46+ cells in healthy and osteosarcoma-bearing canines have phenotypic similarity to human CD3-/NKp46+ NK cells, expressing mRNA for CD16 and the natural cytotoxicity receptors NKp30, NKp44, and NKp80. Functionally, we demonstrate with the calcein release assay that canine CD3-/NKp46+ cells kill canine tumor cell lines without prior sensitization and secrete IFN-γ, TNF-α, IL-8, IL-10, and GM-CSF as measured by Luminex. Like human NK cells, CD3-/NKp46+ cells expand rapidly on feeder cells expressing 4-1BBL and membrane-bound IL-21 (median= 20,283-fold in 21 days. Further, we identify a minor Null population (CD3-/CD21-/CD14-/NKp46- with reduced cytotoxicity against osteosarcoma cells, but similar cytokine secretion as CD3-/NKp46+ cells. Null cells in canines and humans have reduced expression of NKG2D, NKp44, and CD16 compared to NKp46+ NK cells, and can be induced to express NKp46 with further expansion on feeder cells. In conclusion, we have identified and characterized canine NK cells, including an NKp46- subset of canine and human NK cells, using a novel anti-canine NKp46 antibody, and report robust ex vivo expansion of canine NK cells sufficient for adoptive immunotherapy.

  2. Bat Caliciviruses and Human Noroviruses Are Antigenically Similar and Have Overlapping Histo-Blood Group Antigen Binding Profiles.

    Science.gov (United States)

    Kocher, Jacob F; Lindesmith, Lisa C; Debbink, Kari; Beall, Anne; Mallory, Michael L; Yount, Boyd L; Graham, Rachel L; Huynh, Jeremy; Gates, J Edward; Donaldson, Eric F; Baric, Ralph S

    2018-05-22

    Emerging zoonotic viral diseases remain a challenge to global public health. Recent surveillance studies have implicated bats as potential reservoirs for a number of viral pathogens, including coronaviruses and Ebola viruses. Caliciviridae represent a major viral family contributing to emerging diseases in both human and animal populations and have been recently identified in bats. In this study, we blended metagenomics, phylogenetics, homology modeling, and in vitro assays to characterize two novel bat calicivirus (BtCalV) capsid sequences, corresponding to strain BtCalV/A10/USA/2009, identified in Perimyotis subflavus near Little Orleans, MD, and bat norovirus. We observed that bat norovirus formed virus-like particles and had epitopes and receptor-binding patterns similar to those of human noroviruses. To determine whether these observations stretch across multiple bat caliciviruses, we characterized a novel bat calicivirus, BtCalV/A10/USA/2009. Phylogenetic analysis revealed that BtCalV/A10/USA/2009 likely represents a novel Caliciviridae genus and is most closely related to "recoviruses." Homology modeling revealed that the capsid sequences of BtCalV/A10/USA/2009 and bat norovirus resembled human norovirus capsid sequences and retained host ligand binding within the receptor-binding domains similar to that seen with human noroviruses. Both caliciviruses bound histo-blood group antigens in patterns that overlapped those seen with human and animal noroviruses. Taken together, our results indicate the potential for bat caliciviruses to bind histo-blood group antigens and overcome a significant barrier to cross-species transmission. Additionally, we have shown that bat norovirus maintains antigenic epitopes similar to those seen with human noroviruses, providing further evidence of evolutionary descent. Our results reiterate the importance of surveillance of wild-animal populations, especially of bats, for novel viral pathogens. IMPORTANCE Caliciviruses are

  3. Similarity of recombinant human perlecan domain 1 by alternative expression systems bioactive heterogenous recombinant human perlecan D1

    DEFF Research Database (Denmark)

    Ellis, April L; Pan, Wensheng; Yang, Guang

    2010-01-01

    BACKGROUND: Heparan sulfate glycosaminoglycans are diverse components of certain proteoglycans and are known to interact with growth factors as a co-receptor necessary to induce signalling and growth factor activity. In this report we characterize heterogeneously glycosylated recombinant human...... perlecan domain 1 (HSPG2 abbreviated as rhPln.D1) synthesized in either HEK 293 cells or HUVECs by transient gene delivery using either adenoviral or expression plasmid technology. RESULTS: By SDS-PAGE analysis following anion exchange chromatography, the recombinant proteoglycans appeared to possess...... glycosaminoglycan chains ranging, in total, from 6 kDa to >90 kDa per recombinant. Immunoblot analysis of enzyme-digested high Mr rhPln.D1 demonstrated that the rhPln.D1 was synthesized as either a chondroitin sulfate or heparan sulfate proteoglycan, in an approximately 2:1 ratio, with negligible hybrids. Secondary...

  4. Multilayered epithelium in a rat model and human Barrett's esophagus: Similar expression patterns of transcription factors and differentiation markers

    Directory of Open Access Journals (Sweden)

    Yang Chung S

    2008-01-01

    Full Text Available Abstract Background In rats, esophagogastroduodenal anastomosis (EGDA without concomitant chemical carcinogen treatment leads to gastroesophageal reflux disease, multilayered epithelium (MLE, a presumed precursor in intestinal metaplasia, columnar-lined esophagus, dysplasia, and esophageal adenocarcinoma. Previously we have shown that columnar-lined esophagus in EGDA rats resembled human Barrett's esophagus (BE in its morphology, mucin features and expression of differentiation markers (Lab. Invest. 2004;84:753–765. The purpose of this study was to compare the phenotype of rat MLE with human MLE, in order to gain insight into the nature of MLE and its potential role in the development of BE. Methods Serial sectioning was performed on tissue samples from 32 EGDA rats and 13 patients with established BE. Tissue sections were immunohistochemically stained for a variety of transcription factors and differentiation markers of esophageal squamous epithelium and intestinal columnar epithelium. Results We detected MLE in 56.3% (18/32 of EGDA rats, and in all human samples. As expected, both rat and human squamous epithelium, but not intestinal metaplasia, expressed squamous transcription factors and differentiation markers (p63, Sox2, CK14 and CK4 in all cases. Both rat and human intestinal metaplasia, but not squamous epithelium, expressed intestinal transcription factors and differentiation markers (Cdx2, GATA4, HNF1α, villin and Muc2 in all cases. Rat MLE shared expression patterns of Sox2, CK4, Cdx2, GATA4, villin and Muc2 with human MLE. However, p63 and CK14 were expressed in a higher proportion of rat MLE compared to humans. Conclusion These data indicate that rat MLE shares similar properties to human MLE in its expression pattern of these markers, not withstanding small differences, and support the concept that MLE may be a transitional stage in the metaplastic conversion of squamous to columnar epithelium in BE.

  5. Similarities in the immunoglobulin response and VH gene usage in rhesus monkeys and humans exposed to porcine hepatocytes

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    Borie Dominic C

    2006-03-01

    Full Text Available Abstract Background The use of porcine cells and organs as a source of xenografts for human patients would vastly increase the donor pool; however, both humans and Old World primates vigorously reject pig tissues due to xenoantibodies that react with the polysaccharide galactose α (1,3 galactose (αGal present on the surface of many porcine cells. We previously examined the xenoantibody response in patients exposed to porcine hepatocytes via treatment(s with bioartficial liver devices (BALs, composed of porcine cells in a support matrix. We determined that xenoantibodies in BAL-treated patients are predominantly directed at porcine αGal carbohydrate epitopes, and are encoded by a small number of germline heavy chain variable region (VH immunoglobulin genes. The studies described in this manuscript were designed to identify whether the xenoantibody responses and the IgVH genes encoding antibodies to porcine hepatocytes in non-human primates used as preclinical models are similar to those in humans. Adult non-immunosuppressed rhesus monkeys (Macaca mulatta were injected intra-portally with porcine hepatocytes or heterotopically transplanted with a porcine liver lobe. Peripheral blood leukocytes and serum were obtained prior to and at multiple time points after exposure, and the immune response was characterized, using ELISA to evaluate the levels and specificities of circulating xenoantibodies, and the production of cDNA libraries to determine the genes used by B cells to encode those antibodies. Results Xenoantibodies produced following exposure to isolated hepatocytes and solid organ liver grafts were predominantly encoded by genes in the VH3 family, with a minor contribution from the VH4 family. Immunoglobulin heavy-chain gene (VH cDNA library screening and gene sequencing of IgM libraries identified the genes as most closely-related to the IGHV3-11 and IGHV4-59 germline progenitors. One of the genes most similar to IGHV3-11, VH3-11cyno, has

  6. Healthy ageing in the Nun Study: definition and neuropathologic correlates.

    Science.gov (United States)

    Tyas, Suzanne L; Snowdon, David A; Desrosiers, Mark F; Riley, Kathryn P; Markesbery, William R

    2007-11-01

    Although the concept of healthy ageing has stimulated considerable interest, no generally accepted definition has been developed nor has its biological basis been determined. To develop a definition of healthy ageing and investigate its association with longevity and neuropathology. Analyses were based on cognitive, physical, and post-mortem assessments from 1991 to 1998 in the Nun Study, a longitudinal study of ageing in participants 75+ years at baseline. We defined three mutually exclusive levels of healthy ageing (excellent, very good, and good) based on measures of global cognitive function, short-term memory, basic and instrumental activities of daily living, and self-rated function. Mortality analyses were based on 636 participants; neuropathologic analyses were restricted to 221 who had died and were autopsied. Only 11% of those meeting criteria for the excellent level of healthy ageing at baseline subsequently died, compared with 24% for the very good, 39% for the good, and 60% for the remaining participants. Survival curves showed significantly greater longevity with higher levels of healthy ageing. The risk of not attaining healthy ageing, adjusted for age, increased two-fold in participants with brain infarcts alone, six-fold in those with Alzheimer neuropathology alone, and more than thirteen-fold in those with both brain infarcts and Alzheimer neuropathology. The biological validity of our definition of healthy ageing is supported by its strong association with mortality and longevity. Avoiding Alzheimer and stroke neuropathology is critical to the maintenance of healthy ageing, and the presence of both pathologies dramatically decreases the likelihood of healthy ageing.

  7. Distinct contributions of functional and deep neural network features to representational similarity of scenes in human brain and behavior.

    Science.gov (United States)

    Groen, Iris Ia; Greene, Michelle R; Baldassano, Christopher; Fei-Fei, Li; Beck, Diane M; Baker, Chris I

    2018-03-07

    Inherent correlations between visual and semantic features in real-world scenes make it difficult to determine how different scene properties contribute to neural representations. Here, we assessed the contributions of multiple properties to scene representation by partitioning the variance explained in human behavioral and brain measurements by three feature models whose inter-correlations were minimized a priori through stimulus preselection. Behavioral assessments of scene similarity reflected unique contributions from a functional feature model indicating potential actions in scenes as well as high-level visual features from a deep neural network (DNN). In contrast, similarity of cortical responses in scene-selective areas was uniquely explained by mid- and high-level DNN features only, while an object label model did not contribute uniquely to either domain. The striking dissociation between functional and DNN features in their contribution to behavioral and brain representations of scenes indicates that scene-selective cortex represents only a subset of behaviorally relevant scene information.

  8. Xenopus pax6 mutants affect eye development and other organ systems, and have phenotypic similarities to human aniridia patients.

    Science.gov (United States)

    Nakayama, Takuya; Fisher, Marilyn; Nakajima, Keisuke; Odeleye, Akinleye O; Zimmerman, Keith B; Fish, Margaret B; Yaoita, Yoshio; Chojnowski, Jena L; Lauderdale, James D; Netland, Peter A; Grainger, Robert M

    2015-12-15

    Mutations in the Pax6 gene cause ocular defects in both vertebrate and invertebrate animal species, and the disease aniridia in humans. Despite extensive experimentation on this gene in multiple species, including humans, we still do not understand the earliest effects on development mediated by this gene. This prompted us to develop pax6 mutant lines in Xenopus tropicalis taking advantage of the utility of the Xenopus system for examining early development and in addition to establish a model for studying the human disease aniridia in an accessible lower vertebrate. We have generated mutants in pax6 by using Transcription Activator-Like Effector Nuclease (TALEN) constructs for gene editing in X. tropicalis. Embryos with putative null mutations show severe eye abnormalities and changes in brain development, as assessed by changes in morphology and gene expression. One gene that we found is downregulated very early in development in these pax6 mutants is myc, a gene involved in pluripotency and progenitor cell maintenance and likely a mediator of some key pax6 functions in the embryo. Changes in gene expression in the developing brain and pancreas reflect other important functions of pax6 during development. In mutations with partial loss of pax6 function eye development is initially relatively normal but froglets show an underdeveloped iris, similar to the classic phenotype (aniridia) seen in human patients with PAX6 mutations. Other eye abnormalities observed in these froglets, including cataracts and corneal defects, are also common in human aniridia. The frog model thus allows us to examine the earliest deficits in eye formation as a result of pax6 lesions, and provides a useful model for understanding the developmental basis for the aniridia phenotype seen in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Quantification of the rat left ventricle force and Ca2+ -frequency relationships: similarities to dog and human.

    Science.gov (United States)

    Taylor, David G; Parilak, Leonard D; LeWinter, Martin M; Knot, Harm J

    2004-01-01

    To measure and quantify the force-frequency (FFR) and Ca(2+)-frequency (CaFR) relationships in isolated rat left ventricular (LV) muscle at physiological heart rates and compare the obtained FFR to that measured in larger mammalian muscle from dog and human using the same experimental protocol. Rat papillary muscle was isolated from the LV of adult male Sprague-Dawley rats, and dog and human muscles were from free-wall LV biopsies, loaded with the Ca(2+) indicator Fura-2, allowed to recover from isolation trauma and then subjected to direct electrical stimulation while measuring force production and intracellular Ca(2+) transients. We obtained a positive FFR between 1 and 4 Hz that is qualitatively similar to that found in isolated LV epicardial muscle strips from dogs and humans with normal LV function. The FFR reflects the cytosolic Ca(2+) transients in amplitude. Isoproterenol yielded an enhancement in force, but flattening of the FFR, whereas cyclopiazonic acid caused depression of FFR amplitude without changing frequency-dependent shape. We describe an experimental protocol that consistently yields positive FFRs in rat, dog and human LV muscle at stimulation rates between 1 and 4 Hz, without significant qualitative differences. We attribute previously observed negative FFR in rat muscle to an increase in SERCA activity early after excision and preparation of the muscle strips.

  10. Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature

    Science.gov (United States)

    Nelson, Peter T.; Alafuzoff, Irina; Bigio, Eileen H.; Bouras, Constantin; Braak, Heiko; Cairns, Nigel J.; Castellani, Rudolph J.; Crain, Barbara J.; Davies, Peter; Del Tredici, Kelly; Duyckaerts, Charles; Frosch, Matthew P.; Haroutunian, Vahram; Hof, Patrick R.; Hulette, Christine M.; Hyman, Bradley T.; Iwatsubo, Takeshi; Jellinger, Kurt A.; Jicha, Gregory A.; Kövari, Enikö; Kukull, Walter A.; Leverenz, James B.; Love, Seth; Mackenzie, Ian R.; Mann, David M.; Masliah, Eliezer; McKee, Ann C.; Montine, Thomas J.; Morris, John C.; Schneider, Julie A.; Sonnen, Joshua A.; Thal, Dietmar R.; Trojanowski, John Q.; Troncoso, Juan C.; Wisniewski, Thomas; Woltjer, Randall L.; Beach, Thomas G.

    2013-01-01

    Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. β-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective for understanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of Aβ plaques and neurofibrillary tangles. Although Aβ plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles. PMID:22487856

  11. Structural and Sequence Similarities of Hydra Xeroderma Pigmentosum A Protein to Human Homolog Suggest Early Evolution and Conservation

    Directory of Open Access Journals (Sweden)

    Apurva Barve

    2013-01-01

    Full Text Available Xeroderma pigmentosum group A (XPA is a protein that binds to damaged DNA, verifies presence of a lesion, and recruits other proteins of the nucleotide excision repair (NER pathway to the site. Though its homologs from yeast, Drosophila, humans, and so forth are well studied, XPA has not so far been reported from protozoa and lower animal phyla. Hydra is a fresh-water cnidarian with a remarkable capacity for regeneration and apparent lack of organismal ageing. Cnidarians are among the first metazoa with a defined body axis, tissue grade organisation, and nervous system. We report here for the first time presence of XPA gene in hydra. Putative protein sequence of hydra XPA contains nuclear localization signal and bears the zinc-finger motif. It contains two conserved Pfam domains and various characterized features of XPA proteins like regions for binding to excision repair cross-complementing protein-1 (ERCC1 and replication protein A 70 kDa subunit (RPA70 proteins. Hydra XPA shows a high degree of similarity with vertebrate homologs and clusters with deuterostomes in phylogenetic analysis. Homology modelling corroborates the very close similarity between hydra and human XPA. The protein thus most likely functions in hydra in the same manner as in other animals, indicating that it arose early in evolution and has been conserved across animal phyla.

  12. Humans, geometric similarity and the Froude number: is ‘‘reasonably close’’ really close enough?

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    Patricia Ann Kramer

    2012-11-01

    Understanding locomotor energetics is imperative, because energy expended during locomotion, a requisite feature of primate subsistence, is lost to reproduction. Although metabolic energy expenditure can only be measured in extant species, using the equations of motion to calculate mechanical energy expenditure offers unlimited opportunities to explore energy expenditure, particularly in extinct species on which empirical experimentation is impossible. Variability, either within or between groups, can manifest as changes in size and/or shape. Isometric scaling (or geometric similarity requires that all dimensions change equally among all individuals, a condition that will not be met in naturally developing populations. The Froude number (Fr, with lower limb (or hindlimb length as the characteristic length, has been used to compensate for differences in size, but does not account for differences in shape. To determine whether or not shape matters at the intraspecific level, we used a mechanical model that had properties that mimic human variation in shape. We varied crural index and limb segment circumferences (and consequently, mass and inertial parameters among nine populations that included 19 individuals that were of different size. Our goal in the current work is to understand whether shape variation changes mechanical energy sufficiently enough to make shape a critical factor in mechanical and metabolic energy assessments. Our results reaffirm that size does not affect mass-specific mechanical cost of transport (Alexander and Jayes, 1983 among geometrically similar individuals walking at equal Fr. The known shape differences among modern humans, however, produce sufficiently large differences in internal and external work to account for much of the observed variation in metabolic energy expenditure, if mechanical energy is correlated with metabolic energy. Any species or other group that exhibits shape differences should be affected similarly to that which we

  13. Humans, geometric similarity and the Froude number: is ‘‘reasonably close’’ really close enough?

    Science.gov (United States)

    Kramer, Patricia Ann; Sylvester, Adam D.

    2013-01-01

    Summary Understanding locomotor energetics is imperative, because energy expended during locomotion, a requisite feature of primate subsistence, is lost to reproduction. Although metabolic energy expenditure can only be measured in extant species, using the equations of motion to calculate mechanical energy expenditure offers unlimited opportunities to explore energy expenditure, particularly in extinct species on which empirical experimentation is impossible. Variability, either within or between groups, can manifest as changes in size and/or shape. Isometric scaling (or geometric similarity) requires that all dimensions change equally among all individuals, a condition that will not be met in naturally developing populations. The Froude number (Fr), with lower limb (or hindlimb) length as the characteristic length, has been used to compensate for differences in size, but does not account for differences in shape. To determine whether or not shape matters at the intraspecific level, we used a mechanical model that had properties that mimic human variation in shape. We varied crural index and limb segment circumferences (and consequently, mass and inertial parameters) among nine populations that included 19 individuals that were of different size. Our goal in the current work is to understand whether shape variation changes mechanical energy sufficiently enough to make shape a critical factor in mechanical and metabolic energy assessments. Our results reaffirm that size does not affect mass-specific mechanical cost of transport (Alexander and Jayes, 1983) among geometrically similar individuals walking at equal Fr. The known shape differences among modern humans, however, produce sufficiently large differences in internal and external work to account for much of the observed variation in metabolic energy expenditure, if mechanical energy is correlated with metabolic energy. Any species or other group that exhibits shape differences should be affected similarly to

  14. Porphyromonas gulae Has Virulence and Immunological Characteristics Similar to Those of the Human Periodontal Pathogen Porphyromonas gingivalis.

    Science.gov (United States)

    Lenzo, Jason C; O'Brien-Simpson, Neil M; Orth, Rebecca K; Mitchell, Helen L; Dashper, Stuart G; Reynolds, Eric C

    2016-09-01

    Periodontitis is a significant problem in companion animals, and yet little is known about the disease-associated microbiota. A major virulence factor for the human periodontal pathogen Porphyromonas gingivalis is the lysyl- and arginyl-specific proteolytic activity of the gingipains. We screened several Porphyromonas species isolated from companion animals-P. asaccharolytica, P. circumdentaria, P. endodontalis, P. levii, P. gulae, P. macacae, P. catoniae, and P. salivosa-for Lys- and Arg-specific proteolytic activity and compared the epithelial and macrophage responses and induction of alveolar bone resorption of the protease active species to that of Porphyromonas gingivalis Only P. gulae exhibited Lys-and Arg-specific proteolytic activity. The genes encoding the gingipains (RgpA/B and Kgp) were identified in the P. gulae strain ATCC 51700 and all publicly available 12 draft genomes of P. gulae strains. P. gulae ATCC 51700 induced levels of alveolar bone resorption in an animal model of periodontitis similar to those in P. gingivalis W50 and exhibited a higher capacity for autoaggregation and binding to oral epithelial cells with induction of apoptosis. Macrophages (RAW 264.7) were found to phagocytose P. gulae ATCC 51700 and the fimbriated P. gingivalis ATCC 33277 at similar levels. In response to P. gulae ATCC 51700, macrophages secreted higher levels of cytokines than those induced by P. gingivalis ATCC 33277 but lower than those induced by P. gingivalis W50, except for the interleukin-6 response. Our results indicate that P. gulae exhibits virulence characteristics similar to those of the human periodontal pathogen P. gingivalis and therefore may play a key role in the development of periodontitis in companion animals. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  15. Zika Virus: An Emergent Neuropathological Agent

    Science.gov (United States)

    White, Martyn K.; Wollebo, Hassen S.; Beckham, J. David; Tyler, Kenneth L.; Khalili, Kamel

    2016-01-01

    The emergence of Zika virus in the Americas has followed a pattern that is familiar from earlier epidemics of other viruses, where a new disease is introduced into a human population and then spreads rapidly with important public health consequences. In the case of Zika virus, an accumulating body of recent evidence implicates the virus in the etiology of serious pathologies of the human nervous system, that is, the occurrence of microcephaly in neonates and Guillain–Barré syndrome in adults. Zika virus is an arbovirus (arthropod-borne virus) and a member of the family Flaviviridae, genus Flavivirus. Zika virions are enveloped and icosahedral, and contain a nonsegmented, single-stranded, positive-sense RNA genome, which encodes 3 structural and 7 nonstructural proteins that are expressed as a single polyprotein that undergoes cleavage. Zika genomic RNA replicates in the cytoplasm of infected host cells. Zika virus was first detected in 1947 in the blood of a febrile monkey in Uganda’s Zika Forest and in crushed suspensions of the Aedes mosquito, which is one of the vectors for Zika virus. The virus remained obscure, with a few human cases confined to Africa and Asia. There are two lineages of the Zika virus, African and Asian, with the Asian strain causing outbreaks in Micronesia in 2007 and French Polynesia in 2013–2014. From here, the virus spread to Brazil with the first report of autochthonous Zika transmission in the Americas in March 2015. The rapid advance of the virus in the Americas and its likely association with microcephaly and Guillain–Barré syndrome make Zika an urgent public health concern. PMID:27464346

  16. Leptomeninges-Derived Induced Pluripotent Stem Cells and Directly Converted Neurons From Autopsy Cases With Varying Neuropathologic Backgrounds.

    Science.gov (United States)

    Rose, Shannon E; Frankowski, Harald; Knupp, Allison; Berry, Bonnie J; Martinez, Refugio; Dinh, Stephanie Q; Bruner, Lauren T; Willis, Sherry L; Crane, Paul K; Larson, Eric B; Grabowski, Thomas; Darvas, Martin; Keene, C Dirk; Young, Jessica E

    2018-05-01

    Patient-specific stem cell technology from skin and other biopsy sources has transformed in vitro models of neurodegenerative disease, permitting interrogation of the effects of complex human genetics on neurotoxicity. However, the neuropathologic changes that underlie cognitive and behavioral phenotypes can only be determined at autopsy. To better correlate the biology of derived neurons with age-related and neurodegenerative changes, we generated leptomeningeal cell lines from well-characterized research subjects that have undergone comprehensive postmortem neuropathologic examinations. In a series of proof of principle experiments, we reprogrammed autopsy leptomeningeal cell lines to human-induced pluripotent stem cells (hiPSCs) and differentiated these into neurons. We show that leptomeningeal-derived hiPSC lines can be generated from fresh and frozen leptomeninges, are pluripotent, and retain the karyotype of the starting cell population. Additionally, neurons differentiated from these hiPSCs are functional and produce measurable Alzheimer disease-relevant analytes (Aβ and Tau). Finally, we used direct conversion protocols to transdifferentiate leptomeningeal cells to neurons. These resources allow the generation of in vitro models to test mechanistic hypotheses as well as diagnostic and therapeutic strategies in association with neuropathology, clinical and cognitive data, and biomarker studies, aiding in the study of late-onset Alzheimer disease and other age-related neurodegenerative diseases.

  17. Hybrid Capture 2 and cobas human papillomavirus assays perform similarly on SurePath samples from women with abnormalities

    DEFF Research Database (Denmark)

    Fornari, D; Rebolj, M; Bjerregaard, B

    2016-01-01

    OBJECTIVE: In two laboratories (Departments of Pathology, Copenhagen University Hospitals of Herlev and Hvidovre), we compared cobas and Hybrid Capture 2 (HC2) human papillomavirus (HPV) assays using SurePath® samples from women with atypical squamous cells of undetermined significance (ASCUS......) at ≥30 years and women after treatment of cervical intraepithelial neoplasia (CIN). METHODS: Samples from 566 women with ASCUS and 411 women after treatment were routinely tested with HC2 and, thereafter, with cobas. Histological outcomes were retrieved from the Danish Pathology Data Base. We calculated...... the overall agreement between the assays, and compared their sensitivity and specificity for ≥CIN2. RESULTS: In women with ASCUS, HC2 and cobas testing results were similar in the two laboratories. The overall agreement was 91% (95% CI, 88-93). After CIN treatment, the overall agreement was 87% (95% CI, 82...

  18. Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain

    International Nuclear Information System (INIS)

    Volkow, N.D.

    1999-01-01

    The reinforcing effects of cocaine and methylphenidate have been linked to their ability to block dopamine transporters (DAT). Though cocaine and methylphenidate have similar in vitro affinities for DAT the abuse of methylphenidate in humans is substantially lower than of cocaine. To test if differences in in vivo potency at the DAT between these two drugs could account for the differences in their abuse liability the authors compared the levels of DAT occupancies that they had previously reported separately for intravenous methylphenidate in controls and for intravenous cocaine in cocaine abusers. DAT occupancies were measured with Positron Emission Tomography using [ 11 C]cocaine, as a DAT ligand, in 8 normal controls for the methylphenidate study and in 17 active cocaine abusers for the cocaine study. The ratio of the distribution volume of [ 11 C]cocaine in striatum to that in cerebellum, which corresponds to Bmax/Kd+1, was used as measure of DAT availability. Parallel measures were obtained to assess the cardiovascular effects of these two drugs. Methylphenidate and cocaine produced comparable dose-dependent blockage of DAT with an estimated ED 50 for methylphenidate of 0.07 mg/kg and for cocaine of 0.13 mg/kg. Both drugs induced similar increases in heart rate and blood pressure but the duration of the effects were significantly longer for methylphenidate than for cocaine

  19. Quantitative mass spectrometry analysis reveals similar substrate consensus motif for human Mps1 kinase and Plk1.

    Directory of Open Access Journals (Sweden)

    Zhen Dou

    Full Text Available BACKGROUND: Members of the Mps1 kinase family play an essential and evolutionarily conserved role in the spindle assembly checkpoint (SAC, a surveillance mechanism that ensures accurate chromosome segregation during mitosis. Human Mps1 (hMps1 is highly phosphorylated during mitosis and many phosphorylation sites have been identified. However, the upstream kinases responsible for these phosphorylations are not presently known. METHODOLOGY/PRINCIPAL FINDINGS: Here, we identify 29 in vivo phosphorylation sites in hMps1. While in vivo analyses indicate that Aurora B and hMps1 activity are required for mitotic hyper-phosphorylation of hMps1, in vitro kinase assays show that Cdk1, MAPK, Plk1 and hMps1 itself can directly phosphorylate hMps1. Although Aurora B poorly phosphorylates hMps1 in vitro, it positively regulates the localization of Mps1 to kinetochores in vivo. Most importantly, quantitative mass spectrometry analysis demonstrates that at least 12 sites within hMps1 can be attributed to autophosphorylation. Remarkably, these hMps1 autophosphorylation sites closely resemble the consensus motif of Plk1, demonstrating that these two mitotic kinases share a similar substrate consensus. CONCLUSIONS/SIGNIFICANCE: hMps1 kinase is regulated by Aurora B kinase and its autophosphorylation. Analysis on hMps1 autophosphorylation sites demonstrates that hMps1 has a substrate preference similar to Plk1 kinase.

  20. Biochemical characterization of an exonuclease from Arabidopsis thaliana reveals similarities to the DNA exonuclease of the human Werner syndrome protein.

    Science.gov (United States)

    Plchova, Helena; Hartung, Frank; Puchta, Holger

    2003-11-07

    The human Werner syndrome protein (hWRN-p) possessing DNA helicase and exonuclease activities is essential for genome stability. Plants have no homologue of this bifunctional protein, but surprisingly the Arabidopsis genome contains a small open reading frame (ORF) (AtWRNexo) with homology to the exonuclease domain of hWRN-p. Expression of this ORF in Escherichia coli revealed an exonuclease activity for AtWRN-exo-p with similarities but also some significant differences to hWRN-p. The protein digests recessed strands of DNA duplexes in the 3' --> 5' direction but hardly single-stranded DNA or blunt-ended duplexes. In contrast to the Werner exonuclease, AtWRNexo-p is also able to digest 3'-protruding strands. DNA with recessed 3'-PO4 and 3'-OH termini is degraded to a similar extent. AtWRNexo-p hydrolyzes the 3'-recessed strand termini of duplexes containing mismatched bases. AtWRNexo-p needs the divalent cation Mg2+ for activity, which can be replaced by Mn2+. Apurinic sites, cholesterol adducts, and oxidative DNA damage (such as 8-oxoadenine and 8-oxoguanine) inhibit or block the enzyme. Other DNA modifications, including uracil, hypoxanthine and ethenoadenine, did not inhibit AtWRNexo-p. A mutation of a conserved residue within the exonuclease domain (E135A) completely abolished the exonucleolytic activity. Our results indicate that a type of WRN-like exonuclease activity seems to be a common feature of the DNA metabolism of animals and plants.

  1. Neuropathology of mild cognitive impairment (MCI)

    International Nuclear Information System (INIS)

    Murayama, Shigeo; Saito, Yuko

    2007-01-01

    Described are retrospective pathological studies on mild cognitive impairment (MCI) of brain specimens in the brain bank of authors' institute and current clinical studies of outpatients for screening of MCI based on those pathological findings. The study projects, aided by Ministry of Health, Labour and Welfare (MHLW) from 2003 and from 2007, have aimed to develop the optimal way for prophylaxis of dementia. In the former autopsy, about 10% of the elderly dead registered in the institute are found to have pathological changes of the clinical dementia rating 0.5, in whom the early Alzheimer disease (AD), Lewy body dementia, argentaffin granular disease and neurofibrillary tangle dominant disease are involved in a similar ratio to each other. Clinically, new patients with memory complaint are first screened by neurological tests involving CT, and then those with suspicious dementia undergo the second screening (2-day hospitalization) involving MRI with VSRAD (Voxel-based Specific Regional Analysis System for AD), ECD single photon emission computed tomography (SPECT) with eZis (easy Z-score imaging system), myocardial scintigraphy with homovanillic acid (HVA)/m-iodobenzylguanidine (MIBG), and if necessary, PET with fluorodeoxyglucose (FDG), PIB (Pittsburgh Compound B, an amyloid prove) and/or 11 C-CFT and 11 C-raclopride. Further, new patients with suspicious Parkinson disease undergo the screening (3-day) of various tests involving MRI with voxel-based morphometry and VSRAD, cerebral blood flow ECD SPECT with eZis and MIBG myocardial scintigraphy. It is concluded that AD is the most important subject in MCI and systemic diseases can also affect the cognitive ability as well. (R.T.)

  2. Clinical phenotype-based gene prioritization: an initial study using semantic similarity and the human phenotype ontology.

    Science.gov (United States)

    Masino, Aaron J; Dechene, Elizabeth T; Dulik, Matthew C; Wilkens, Alisha; Spinner, Nancy B; Krantz, Ian D; Pennington, Jeffrey W; Robinson, Peter N; White, Peter S

    2014-07-21

    Exome sequencing is a promising method for diagnosing patients with a complex phenotype. However, variant interpretation relative to patient phenotype can be challenging in some scenarios, particularly clinical assessment of rare complex phenotypes. Each patient's sequence reveals many possibly damaging variants that must be individually assessed to establish clear association with patient phenotype. To assist interpretation, we implemented an algorithm that ranks a given set of genes relative to patient phenotype. The algorithm orders genes by the semantic similarity computed between phenotypic descriptors associated with each gene and those describing the patient. Phenotypic descriptor terms are taken from the Human Phenotype Ontology (HPO) and semantic similarity is derived from each term's information content. Model validation was performed via simulation and with clinical data. We simulated 33 Mendelian diseases with 100 patients per disease. We modeled clinical conditions by adding noise and imprecision, i.e. phenotypic terms unrelated to the disease and terms less specific than the actual disease terms. We ranked the causative gene against all 2488 HPO annotated genes. The median causative gene rank was 1 for the optimal and noise cases, 12 for the imprecision case, and 60 for the imprecision with noise case. Additionally, we examined a clinical cohort of subjects with hearing impairment. The disease gene median rank was 22. However, when also considering the patient's exome data and filtering non-exomic and common variants, the median rank improved to 3. Semantic similarity can rank a causative gene highly within a gene list relative to patient phenotype characteristics, provided that imprecision is mitigated. The clinical case results suggest that phenotype rank combined with variant analysis provides significant improvement over the individual approaches. We expect that this combined prioritization approach may increase accuracy and decrease effort for

  3. The proximal first exon architecture of the murine ghrelin gene is highly similar to its human orthologue

    Directory of Open Access Journals (Sweden)

    Seim Inge

    2009-05-01

    Full Text Available Abstract Background The murine ghrelin gene (Ghrl, originally sequenced from stomach tissue, contains five exons and a single transcription start site in a short, 19 bp first exon (exon 0. We recently isolated several novel first exons of the human ghrelin gene and found evidence of a complex transcriptional repertoire. In this report, we examined the 5' exons of the murine ghrelin orthologue in a range of tissues using 5' RACE. Findings 5' RACE revealed two transcription start sites (TSSs in exon 0 and four TSSs in intron 0, which correspond to 5' extensions of exon 1. Using quantitative, real-time RT-PCR (qRT-PCR, we demonstrated that extended exon 1 containing Ghrl transcripts are largely confined to the spleen, adrenal gland, stomach, and skin. Conclusion We demonstrate that multiple transcription start sites are present in exon 0 and an extended exon 1 of the murine ghrelin gene, similar to the proximal first exon organisation of its human orthologue. The identification of several transcription start sites in intron 0 of mouse ghrelin (resulting in an extension of exon 1 raises the possibility that developmental-, cell- and tissue-specific Ghrl mRNA species are created by employing alternative promoters and further studies of the murine ghrelin gene are warranted.

  4. The Cultural Argument for Understanding Nature of Science. A Chance to Reflect on Similarities and Differences Between Science and Humanities

    Science.gov (United States)

    Reiners, Christiane S.; Bliersbach, Markus; Marniok, Karl

    2017-07-01

    , and the role of technology. Thus, the cultural argument for understanding science invites us not only to consider domain-specific concepts but also to reflect on similarities between science and the humanities by way of examples.

  5. Fingerprinting of near-homogeneous DNA ligase I and II from human cells. Similarity of their AMP-binding domains.

    Science.gov (United States)

    Yang, S W; Becker, F F; Chan, J Y

    1990-10-25

    DNA ligases play obligatory roles during replication, repair, and recombination. Multiple forms of DNA ligase have been reported in mammalian cells including DNA ligase I, the high molecular mass species which functions during replication, and DNA ligase II, the low molecular mass species which is associated with repair. In addition, alterations in DNA ligase activities have been reported in acute lymphocytic leukemia cells, Bloom's syndrome cells, and cells undergoing differentiation and development. To better distinguish the biochemical and molecular properties of the various DNA ligases from human cells, we have developed a method of purifying multiple species of DNA ligase from HeLa cells by chromatography through DEAE-Bio-Gel, CM-Bio-Gel, hydroxylapatite, Sephacryl S-300, Mono P, and DNA-cellulose. DNA-cellulose chromatography of the partially purified enzymes resolved multiple species of DNA ligase after labeling the enzyme with [alpha-32P]ATP to form the ligase-[32P]AMP adduct. The early eluting enzyme activity (0.25 M NaCl) contained a major 67-kDa-labeled protein, while the late eluting activity (0.48 M NaCl) contained two major labeled proteins of 90 and 78 kDa. Neutralization experiments with antiligase I antibodies indicated that the early and late eluting activity peaks were DNA ligase II and I, respectively. The three major ligase-[32P]AMP polypeptides (90, 78, and 67 kDa) were subsequently purified to near homogeneity by elution from preparative sodium dodecyl sulfate-polyacrylamide gels. All three polypeptides retained DNA ligase activities after gel elution and renaturation. To further reveal the relationship between these enzymes, partial digestion by V8-protease was performed. All three purified polypeptides gave rise to a common 22-kDa-labeled fragment for their AMP-binding domains, indicating that the catalytic sites of ligase I and II are quite similar, if not identical. Similar findings were obtained from the two-dimensional gel

  6. African ancestry protects against Alzheimer's disease-related neuropathology.

    Science.gov (United States)

    Schlesinger, D; Grinberg, L T; Alba, J G; Naslavsky, M S; Licinio, L; Farfel, J M; Suemoto, C K; de Lucena Ferretti, R E; Leite, R E P; de Andrade, M P; dos Santos, A C F; Brentani, H; Pasqualucci, C A; Nitrini, R; Jacob-Filho, W; Zatz, M

    2013-01-01

    Previous studies in dementia epidemiology have reported higher Alzheimer's disease rates in African-Americans when compared with White Americans. To determine whether genetically determined African ancestry is associated with neuropathological changes commonly associated with dementia, we analyzed a population-based brain bank in the highly admixed city of São Paulo, Brazil. African ancestry was estimated through the use of previously described ancestry-informative markers. Risk of presence of neuritic plaques, neurofibrillary tangles, small vessel disease, brain infarcts and Lewy bodies in subjects with significant African ancestry versus those without was determined. Results were adjusted for multiple environmental risk factors, demographic variables and apolipoprotein E genotype. African ancestry was inversely correlated with neuritic plaques (P=0.03). Subjects with significant African ancestry (n=112, 55.4%) showed lower prevalence of neuritic plaques in the univariate analysis (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.55-0.95, P=0.01) and when adjusted for age, sex, APOE genotype and environmental risk factors (OR 0.43, 95% CI 0.21-0.89, P=0.02). There were no significant differences for the presence of other neuropathological alterations. We show for the first time, using genetically determined ancestry, that African ancestry may be highly protective of Alzheimer's disease neuropathology, functioning through either genetic variants or unknown environmental factors. Epidemiological studies correlating African-American race/ethnicity with increased Alzheimer's disease rates should not be interpreted as surrogates of genetic ancestry or considered to represent African-derived populations from the developing nations such as Brazil.

  7. Genetically similar strains of Escherichia coli O157:H7 isolated from sheep, cattle and human patients

    Directory of Open Access Journals (Sweden)

    Söderlund Robert

    2012-10-01

    Full Text Available Abstract Background Comparatively little is known about the prevalence or the molecular characteristics of the zoonotic pathogen E. coli O157:H7 in the sheep reservoir. To investigate this and determine the host specificity of subclones of the bacterium, we have conducted a slaughterhouse prevalence study in sheep and compared the collected isolates to O157:H7 previously isolated from cattle and human patients. Results Verotoxin-producing O157:H7 was found in 11/597 (1.8% of samples from sheep in Swedish slaughterhouses, 9/492 faecal (1.8% and 2/105 ear samples (1.9%. All positive sheep were eaeA, hlyA, cdtV-B, vtx1, and partial sequencing of vtx2. The observed profiles were similar to those of cattle strains investigated previously. Conclusions The same pathogenic subtypes of VTEC O157:H7, including the highly virulent clade 8, appear to be present in both sheep and cattle in Sweden, suggesting strains can circulate freely between ruminant reservoirs.

  8. Temporal-pattern similarity analysis reveals the beneficial and detrimental effects of context reinstatement on human memory.

    Science.gov (United States)

    Staudigl, Tobias; Vollmar, Christian; Noachtar, Soheyl; Hanslmayr, Simon

    2015-04-01

    A powerful force in human memory is the context in which memories are encoded (Tulving and Thomson, 1973). Several studies suggest that the reinstatement of neural encoding patterns is beneficial for memory retrieval (Manning et al., 2011; Staresina et al., 2012; Jafarpour et al., 2014). However, reinstatement of the original encoding context is not always helpful, for instance, when retrieving a memory in a different contextual situation (Smith and Vela, 2001). It is an open question whether such context-dependent memory effects can be captured by the reinstatement of neural patterns. We investigated this question by applying temporal and spatial pattern similarity analysis in MEG and intracranial EEG in a context-match paradigm. Items (words) were tagged by individual dynamic context stimuli (movies). The results show that beta oscillatory phase in visual regions and the parahippocampal cortex tracks the incidental reinstatement of individual context trajectories on a single-trial level. Crucially, memory benefitted from reinstatement when the encoding and retrieval contexts matched but suffered from reinstatement when the contexts did not match. Copyright © 2015 the authors 0270-6474/15/355373-12$15.00/0.

  9. Stretchable human-machine interface based on skin-conformal sEMG electrodes with self-similar geometry

    Science.gov (United States)

    Dong, Wentao; Zhu, Chen; Hu, Wei; Xiao, Lin; Huang, Yong'an

    2018-01-01

    Current stretchable surface electrodes have attracted increasing attention owing to their potential applications in biological signal monitoring, wearable human-machine interfaces (HMIs) and the Internet of Things. The paper proposed a stretchable HMI based on a surface electromyography (sEMG) electrode with a self-similar serpentine configuration. The sEMG electrode was transfer-printed onto the skin surface conformally to monitor biological signals, followed by signal classification and controlling of a mobile robot. Such electrodes can bear rather large deformation (such as >30%) under an appropriate areal coverage. The sEMG electrodes have been used to record electrophysiological signals from different parts of the body with sharp curvature, such as the index finger, back of the neck and face, and they exhibit great potential for HMI in the fields of robotics and healthcare. The electrodes placed onto the two wrists would generate two different signals with the fist clenched and loosened. It is classified to four kinds of signals with a combination of the gestures from the two wrists, that is, four control modes. Experiments demonstrated that the electrodes were successfully used as an HMI to control the motion of a mobile robot remotely. Project supported by the National Natural Science Foundation of China (Nos. 51635007, 91323303).

  10. Scanning electron microscopy of the neuropathology of murine cerebral malaria

    Directory of Open Access Journals (Sweden)

    Brenneis Christian

    2006-11-01

    Full Text Available Abstract Background The mechanisms leading to death and functional impairments due to cerebral malaria (CM are yet not fully understood. Most of the knowledge about the pathomechanisms of CM originates from studies in animal models. Though extensive histopathological studies of the murine brain during CM are existing, alterations have not been visualized by scanning electron microscopy (SEM so far. The present study investigates the neuropathological features of murine CM by applying SEM. Methods C57BL/6J mice were infected with Plasmodium berghei ANKA blood stages. When typical symptoms of CM developed perfused brains were processed for SEM or light microscopy, respectively. Results Ultrastructural hallmarks were disruption of vessel walls, parenchymal haemorrhage, leukocyte sequestration to the endothelium, and diapedesis of macrophages and lymphocytes into the Virchow-Robin space. Villous appearance of observed lymphocytes were indicative of activated state. Cerebral oedema was evidenced by enlargement of perivascular spaces. Conclusion The results of the present study corroborate the current understanding of CM pathophysiology, further support the prominent role of the local immune system in the neuropathology of CM and might expose new perspectives for further interventional studies.

  11. Neuropathologic Studies of the Baltimore Longitudinal Study of Aging (BLSA)

    Science.gov (United States)

    O’Brien, Richard J.; Resnick, Susan M.; Zonderman, Alan B.; Ferrucci, Luigi; Crain, Barbara J.; Pletnikova, Olga; Rudow, Gay; Iacono, Diego; Riudavets, Miguel A.; Driscoll, Ira; Price, Donald L.; Martin, Lee J.; Troncoso, Juan C.

    2010-01-01

    The Baltimore Longitudinal Study of Aging (BLSA) was established in 1958 and is one the oldest prospective studies of aging in the USA and the world. The BLSA is supported by the National Institute of Aging (NIA) and its mission is to learn what happens to people as they get old and how to sort out changes due to aging and from those due to disease or other causes. In 1986, an autopsy program combined with comprehensive neurologic and cognitive evaluations was established in collaboration with the Johns Hopkins University Alzheimer’s Disease Research Center (ADRC). Since then, 211 subjects have undergone autopsy. Here we review the key clinical neuropathological correlations from this autopsy series. The focus is on the morphological and biochemical changes that occur in normal aging, and the early neuropathological changes of neurodegenerative diseases, especially Alzheimer’s disease (AD). We highlight the combined clinical, pathologic, morphometric, and biochemical evidence of asymptomatic AD, a state characterized by normal clinical evaluations in subjects with abundant AD pathology. We conclude that in some individuals, successful cognitive aging results from compensatory mechanisms that occur at the neuronal level (i.e., neuronal hypertrophy and synaptic plasticity) whereas a failure of compensation may culminate in disease. PMID:19661626

  12. Severe neonatal epileptic encephalopathy and KCNQ2 mutation: neuropathological substrate?

    Directory of Open Access Journals (Sweden)

    Charlotte eDalen Meurs-Van Der Schoor

    2014-12-01

    Full Text Available Background:Neonatal convulsions are clinical manifestations in a heterogeneous group of disorders with different etiology and outcome. They are attributed to several genetic causes. Methods:We describe a patient with intractable neonatal seizures who died from respiratory compromise during a status epilepticus. Results:This case report provides EEG, MRI, genetic analysis and neuropathological data. Genetic analysis revealed a de novo heterozygous missense mutation in the KCNQ2 gene, which encodes a subunit of a voltage-gated potassium channel. KCNQ2 gene mutation is associated with intractable neonatal seizures. EEG, MRI data as well as mutation analysis have been described in other KCNQ2 cases. Postmortem neuropathologic investigation revealed mild malformation of cortical development with increased heterotopic neurons in the deep white matter compared to an age-matched control subject. The new finding of this study is the combination of a KCNQ2 mutation and the cortical abnormalities. Conclusions:KCNQ2 mutations should be considered in neonates with refractory epilepsy of unknown cause. The mild cortical malformation is an important new finding, though it remains unknown whether these cortical abnormalities are due to the KCNQ2 mutation or are secondary to the refractory seizures.

  13. Neuropathologies of the self: clinical and anatomical features.

    Science.gov (United States)

    Feinberg, Todd E

    2011-03-01

    The neuropathologies of the self (NPS) are disorders of the self and identity that occur in association with neuropathology and include perturbations of the bodily, relational, and narrative self. Right, especially medial-frontal and orbitofrontal lesions, are associated with these conditions. The ego disequilibrium theory proposes this brain pathology causes a disturbance of ego boundaries and functions and the emergence of developmentally immature styles of thought, ego functioning, and psychological defenses including denial, projection, splitting, and fantasy that the NPS patient has in common with the child. I hypothesize that during brain development between approximately ages 3 and 7 immature defensive functions and fantasies tend to be replaced by mature defenses and the inhibition of fantasy a process that depends upon maturational processes within the right hemisphere. I propose a four-tiered model of the NPS that emphasizes a multifactorial approach and includes both negative and positive, bottom up and top down, and neuropsychological and psychological factors. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. [Neuropathology in the neurosciences. A system in transition].

    Science.gov (United States)

    Seitelberger, F

    1993-08-01

    Neuropathology (Np) is a full member of the neurosciences. As a basic neuroscience it is directed to the behaviour of nervous tissues under pathogenic conditions. The theoretical and methodical core of Np concerns the morphological features of pathological disorders and processes of the nervous system. The goal of Np data presentation is an objective description of the structural changes; their time course as processes, and if possible their causal constellations. Complementary to this analytical task is that of reconstructing the pathological process and at a higher level the conception of pathomorphological entities, e.g. as syndromes. Clinical Np is an alliance of Np with neurology, psychiatry and neurosurgery for representing the structural basis of diseases and the role of morphology in diagnosis and clinical management. Prerequisite for the proper functioning of Np is an integration with these other specialist fields. The clinical neuropathologist therefore has to be in certain respects also a neurologist. The same is true of the alliances of Np with other neurosciences, which is already reflected in recent neuropathological methodology. Detailed training programs are necessary for clinical Np, covering all aspects of its medical and social implications. Enough options should be offered for horizontal flexibility of curricula, futherance of secondary special training and support of good unconventional approaches by junior scientists.

  15. Interactive exploration of the vulnerability of the human infrastructure: an approach using simultaneous display of similar locations

    Science.gov (United States)

    Ceré, Raphaël; Kaiser, Christian

    2015-04-01

    Currently, three quarters of the Swiss population is living in urban areas. The total population is still increasing, and urbanized space is increasing event faster. Consequently, the intensity of use has decreased but the exposure of the urban space to natural events has grown along with the cost related to the impact of hazards. In line with this fact, during the 20th century there has been a noticeable increase of natural disasters accompanied by the rapid increase of the world population, leading to higher costs. Additionally to the fact that more people are exposed to natural hazards, the value of goods globally has increased more than proportionally. Consequently, the vulnerability of urban space is, more than ever before, a major issue for socio-economic development. Here, vulnerability is defined as the potential human loss or loss of infrastructure caused by a hazardous event. It encompasses factors of urban infrastructure, population and the environment, which increase the susceptibility of a location to the impact of hazards. This paper describes a novel method for improving the interactive use of exploratory data analysis in the context of minimizing vulnerability and disaster risk by prevention or mitigation. This method is used to assess the similarity between different locations with respect to several characteristics relevant to vulnerability at different scales, allowing for automatic display of multiple locations similar to the one under investigation by an expert. Visualizing vulnerability simultaneously for several locations allows for analyzing and comparing of metric characteristics between multiple places and at different scales. The interactivity aspect is also useful for understanding vulnerability patterns and it facilitates disaster risk management and decisions on global preventive measures in urban spaces. Metrics for vulnerability assessment can be extracted from extensive geospatial datasets such as high-resolution digital elevation

  16. Clinical and neuropathological features of ALS/FTD with TIA1 mutations.

    Science.gov (United States)

    Hirsch-Reinshagen, Veronica; Pottier, Cyril; Nicholson, Alexandra M; Baker, Matt; Hsiung, Ging-Yuek R; Krieger, Charles; Sengdy, Pheth; Boylan, Kevin B; Dickson, Dennis W; Mesulam, Marsel; Weintraub, Sandra; Bigio, Eileen; Zinman, Lorne; Keith, Julia; Rogaeva, Ekaterina; Zivkovic, Sasha A; Lacomis, David; Taylor, J Paul; Rademakers, Rosa; Mackenzie, Ian R A

    2017-12-07

    Mutations in the stress granule protein T-cell restricted intracellular antigen 1 (TIA1) were recently shown to cause amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD). Here, we provide detailed clinical and neuropathological descriptions of nine cases with TIA1 mutations, together with comparisons to sporadic ALS (sALS) and ALS due to repeat expansions in C9orf72 (C9orf72+). All nine patients with confirmed mutations in TIA1 were female. The clinical phenotype was heterogeneous with a range in the age at onset from late twenties to the eighth decade (mean = 60 years) and disease duration from one to 6 years (mean = 3 years). Initial presentation was either focal weakness or language impairment. All affected individuals received a final diagnosis of ALS with or without FTD. No psychosis or parkinsonism was described. Neuropathological examination on five patients found typical features of ALS and frontotemporal lobar degeneration (FTLD-TDP, type B) with anatomically widespread TDP-43 proteinopathy. In contrast to C9orf72+ cases, caudate atrophy and hippocampal sclerosis were not prominent. Detailed evaluation of the pyramidal motor system found a similar degree of neurodegeneration and TDP-43 pathology as in sALS and C9orf72+ cases; however, cases with TIA1 mutations had increased numbers of lower motor neurons containing round eosinophilic and Lewy body-like inclusions on HE stain and round compact cytoplasmic inclusions with TDP-43 immunohistochemistry. Immunohistochemistry and immunofluorescence failed to demonstrate any labeling of inclusions with antibodies against TIA1. In summary, our TIA1 mutation carriers developed ALS with or without FTD, with a wide range in age at onset, but without other neurological or psychiatric features. The neuropathology was characterized by widespread TDP-43 pathology, but a more restricted pattern of neurodegeneration than C9orf72+ cases. Increased numbers of round eosinophilic and Lewy

  17. Assessment of bioaccumulation, neuropathology, and neurobehavior following subchronic (90 days) inhalation in Sprague-Dawley rats exposed to manganese phosphate.

    Science.gov (United States)

    Normandin, Louise; Carrier, Gaétan; Gardiner, Phillip F; Kennedy, Greg; Hazell, Alan S; Mergler, Donna; Butterworth, Roger F; Philippe, Suzanne; Zayed, Joseph

    2002-09-01

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline. It has been suggested that the combustion products of MMT containing Mn, such as manganese phosphate, could cause neurological symptoms similar to Parkinson's disease in humans. The aim of this work was to investigate the exposure-response relationship of bioaccumulation, neuropathology, and neurobehavior following a subchronic inhalation exposure to manganese phosphate in Sprague-Dawley male rats. Rats were exposed 6 h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3000 microg/m(3) Mn phosphate and compared to controls. Some rats were implanted with chronic EMG electrodes in the gastrocnemius muscle of the hind limb to assess tremor at the end of Mn exposure. Spontaneous motor activity was measured for 36 h using a computerized autotrack system. Rats were then sacrificed by exsanguination and Mn level in different brain tissues and other organs was determined by instrumental neutron activation analysis. Neuronal cell counts were obtained by assessing the sum of five grid areas for the caudate/putamen and the sum of two adjacent areas for the globus pallidus. Increased manganese concentrations were observed in all tissues of the brain and was dose-dependent in olfactory bulb and caudate/putamen. In fact, beginning with the highest level of exposure (3000 microg/m(3)) and ending with the control group, Mn concentrations in the olfactory bulb were 2.47 vs 1.28 vs 0.77 vs 0.64 ppm (P Locomotor activity assessment and tremor assessment did not reveal in neurobehavioral changes between the groups. Our results reinforce the hypothesis that the olfactory bulb and caudate/putamen are the main brain tissues for Mn accumulation after subchronic inhalation exposure.

  18. Neuropathologic features of the hippocampus and amygdala in cats with familial spontaneous epilepsy.

    Science.gov (United States)

    Yu, Yoshihiko; Hasegawa, Daisuke; Hamamoto, Yuji; Mizoguchi, Shunta; Kuwabara, Takayuki; Fujiwara-Igarashi, Aki; Tsuboi, Masaya; Chambers, James Ken; Fujita, Michio; Uchida, Kazuyuki

    2018-03-01

    OBJECTIVE To investigate epilepsy-related neuropathologic changes in cats of a familial spontaneous epileptic strain (ie, familial spontaneous epileptic cats [FSECs]). ANIMALS 6 FSECs, 9 age-matched unrelated healthy control cats, and 2 nonaffected (without clinical seizures)dams and 1 nonaffected sire of FSECs. PROCEDURES Immunohistochemical analyses were used to evaluate hippocampal sclerosis, amygdaloid sclerosis, mossy fiber sprouting, and granule cell pathological changes. Values were compared between FSECs and control cats. RESULTS Significantly fewer neurons without gliosis were detected in the third subregion of the cornu ammonis (CA) of the dorsal and ventral aspects of the hippocampus as well as the central nucleus of the amygdala in FSECs versus control cats. Gliosis without neuronal loss was also observed in the CA4 subregion of the ventral aspect of the hippocampus. No changes in mossy fiber sprouting and granule cell pathological changes were detected. Moreover, similar changes were observed in the dams and sire without clinical seizures, although to a lesser extent. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that the lower numbers of neurons in the CA3 subregion of the hippocampus and the central nucleus of the amygdala were endophenotypes of familial spontaneous epilepsy in cats. In contrast to results of other veterinary medicine reports, severe epilepsy-related neuropathologic changes (eg, hippocampal sclerosis, amygdaloid sclerosis, mossy fiber sprouting, and granule cell pathological changes) were not detected in FSECs. Despite the use of a small number of cats with infrequent seizures, these findings contributed new insights on the pathophysiologic mechanisms of genetic-related epilepsy in cats.

  19. A path-based measurement for human miRNA functional similarities using miRNA-disease associations

    Science.gov (United States)

    Ding, Pingjian; Luo, Jiawei; Xiao, Qiu; Chen, Xiangtao

    2016-09-01

    Compared with the sequence and expression similarity, miRNA functional similarity is so important for biology researches and many applications such as miRNA clustering, miRNA function prediction, miRNA synergism identification and disease miRNA prioritization. However, the existing methods always utilized the predicted miRNA target which has high false positive and false negative to calculate the miRNA functional similarity. Meanwhile, it is difficult to achieve high reliability of miRNA functional similarity with miRNA-disease associations. Therefore, it is increasingly needed to improve the measurement of miRNA functional similarity. In this study, we develop a novel path-based calculation method of miRNA functional similarity based on miRNA-disease associations, called MFSP. Compared with other methods, our method obtains higher average functional similarity of intra-family and intra-cluster selected groups. Meanwhile, the lower average functional similarity of inter-family and inter-cluster miRNA pair is obtained. In addition, the smaller p-value is achieved, while applying Wilcoxon rank-sum test and Kruskal-Wallis test to different miRNA groups. The relationship between miRNA functional similarity and other information sources is exhibited. Furthermore, the constructed miRNA functional network based on MFSP is a scale-free and small-world network. Moreover, the higher AUC for miRNA-disease prediction indicates the ability of MFSP uncovering miRNA functional similarity.

  20. The importance of brain banks for molecular neuropathological research: The New South Wales Tissue Resource Centre experience.

    Science.gov (United States)

    Dedova, Irina; Harding, Antony; Sheedy, Donna; Garrick, Therese; Sundqvist, Nina; Hunt, Clare; Gillies, Juliette; Harper, Clive G

    2009-01-01

    New developments in molecular neuropathology have evoked increased demands for postmortem human brain tissue. The New South Wales Tissue Resource Centre (TRC) at The University of Sydney has grown from a small tissue collection into one of the leading international brain banking facilities, which operates with best practice and quality control protocols. The focus of this tissue collection is on schizophrenia and allied disorders, alcohol use disorders and controls. This review highlights changes in TRC operational procedures dictated by modern neuroscience, and provides examples of applications of modern molecular techniques to study the neuropathogenesis of many different brain disorders.

  1. Neuropathological and biochemical criteria to identify acquired Creutzfeldt-Jakob disease among presumed sporadic cases.

    Science.gov (United States)

    Kobayashi, Atsushi; Parchi, Piero; Yamada, Masahito; Mohri, Shirou; Kitamoto, Tetsuyuki

    2016-06-01

    As an experimental model of acquired Creutzfeldt-Jakob disease (CJD), we performed transmission studies of sporadic CJD using knock-in mice expressing human prion protein (PrP). In this model, the inoculation of the sporadic CJD strain V2 into animals homozygous for methionine at polymorphic codon 129 (129 M/M) of the PRNP gene produced quite distinctive neuropathological and biochemical features, that is, widespread kuru plaques and intermediate type abnormal PrP (PrP(Sc) ). Interestingly, this distinctive combination of molecular and pathological features has been, to date, observed in acquired CJD but not in sporadic CJD. Assuming that these distinctive phenotypic traits are specific for acquired CJD, we revisited the literature and found two cases showing widespread kuru plaques despite the 129 M/M genotype, in a neurosurgeon and in a patient with a medical history of neurosurgery without dura mater grafting. By Western blot analysis of brain homogenates, we revealed the intermediate type of PrP(Sc) in both cases. Furthermore, transmission properties of brain extracts from these two cases were indistinguishable from those of a subgroup of dura mater graft-associated iatrogenic CJD caused by infection with the sporadic CJD strain V2. These data strongly suggest that the two atypical CJD cases, previously thought to represent sporadic CJD, very likely acquired the disease through exposure to prion-contaminated brain tissues. Thus, we propose that the distinctive combination of 129 M/M genotype, kuru plaques, and intermediate type PrP(Sc) , represents a reliable criterion for the identification of acquired CJD cases among presumed sporadic cases. © 2015 Japanese Society of Neuropathology.

  2. Caco-2 accumulation of lutein is greater from human milk than from infant formula despite similar bioaccessibility.

    Science.gov (United States)

    Lipkie, Tristan E; Banavara, Dattatreya; Shah, Bhavini; Morrow, Ardythe L; McMahon, Robert J; Jouni, Zeina E; Ferruzzi, Mario G

    2014-10-01

    Clinical evidence suggests that the bioavailability of lutein is lower from infant formula than from human milk. The purpose of this study was to assess characteristics of human milk and lutein-fortified infant formula that may impact carotenoid delivery. Carotenoid bioaccessibility and intestinal absorption were modeled by in vitro digestion coupled with Caco-2 human intestinal cell culture. Twelve human milk samples were assessed from 1-6 months postpartum, and 10 lutein-fortified infant formula samples from three lutein sources in both ready-to-use and reconstituted powder forms. The relative bioaccessibility of lutein was not different (p > 0.05) between human milk (29 ± 2%) and infant formula (36 ± 4%). However, lutein delivery was 4.5 times greater from human milk than infant formula when including Caco-2 accumulation efficiency. Caco-2 accumulation of lutein was increasingly efficient with decreasing concentration of lutein from milk. Carotenoid bioaccessibility and Caco-2 accumulation were not affected by lactation stage, total lipid content, lutein source, or form of infant formula (powder vs. liquid). These data suggest that the bioavailability of carotenoids is greater from human milk than infant formula primarily due to intestinal absorptive processes, and that absorption of lutein is potentiated by factors from human milk especially at low lutein concentration. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Human Clay Models versus Cat Dissection: How the Similarity between the Classroom and the Exam Affects Student Performance

    Science.gov (United States)

    Waters, John R.; Van Meter, Peggy; Perrotti, William; Drogo, Salvatore; Cyr, Richard J.

    2011-01-01

    This study examined the effect of different anatomic representations on student learning in a human anatomy class studying the muscular system. Specifically, we examined the efficacy of using dissected cats (with and without handouts) compared with clay sculpting of human structures. Ten undergraduate laboratory sections were assigned to three…

  4. Tooth loss, dementia and neuropathology in the Nun study.

    Science.gov (United States)

    Stein, Pamela Sparks; Desrosiers, Mark; Donegan, Sara Jean; Yepes, Juan F; Kryscio, Richard J

    2007-10-01

    Numerous studies have linked dementia to the subsequent deterioration of oral health. Few investigators, however, have examined oral disease as a potential risk factor in the development of dementia. The authors conducted a study to investigate a potential association between a history of oral disease and the development of dementia. Longitudinal dental records supplemented data collected from 10 annual cognitive assessments of 144 Milwaukee participants in the Nun Study, a longitudinal study of aging and Alzheimer disease, who were 75 to 98 years old. Neuropathologic findings at autopsy were available for 118 participants who died. A low number of teeth increased the risk of higher prevalence and incidence of dementia. Participants with the fewest teeth had the highest risk of prevalence and incidence of dementia. Edentulism or very few (one to nine) teeth may be predictors of dementia late in life.

  5. The neuropathology of morality: Germany 1930-1960.

    Science.gov (United States)

    Schirmann, Felix

    2014-01-01

    This article analyzes brain scientists' attempts to trace morality in the brain in Germany from 1930 to 1960. The debate around Karl Kleist's localization of the Gemeinschafts-Ich [community-I] in the 1930s is depicted in order to illustrate the central arguments for and against localizations of morality. The focus of this article is on the period 1936-1960 in which experts put forth specific ideas on morality's cerebral underpinnings that mirror the larger theoretical shift from strict localization doctrine to a more holistic understanding of the brain. As a result of this shift, experts avoided exact localizations of morality. Instead, they posited correlations between brain areas and morality. The analysis illustrates the dependence of neuropathological research on morality on general theories of brain functioning and marks a first contribution to the history of the neuroscience of morality for the time after 1930.

  6. Linking Essential Tremor to the Cerebellum: Neuropathological Evidence.

    Science.gov (United States)

    Louis, Elan D

    2016-06-01

    A fundamental question about essential tremor (ET) is whether its associated pathological changes and disease mechanisms are linkable to a specific brain region. To that end, recent tissue-based studies have made significant strides in elucidating changes in the ET brain. Emerging from these studies is increasing neuropathological evidence linking ET to the cerebellum. These studies have systematically identified a broad range of structural, degenerative changes in the ET cerebellum, spanning across all Purkinje cell compartments. These include the dendritic compartment (where there is an increase in number of Purkinje cell dendritic swellings, a pruning of the dendritic arbor, and a reduction in spine density), the cell body (where, aside from reductions in Purkinje cell linear density in some studies, there is an increase in the number of heterotopic Purkinje cell soma), and the axonal compartment (where a plethora of changes in axonal morphology have been observed, including an increase in the number of thickened axonal profiles, torpedoes, axonal recurrent collaterals, axonal branching, and terminal axonal sprouting). Additional changes, possibly due to secondary remodeling, have been observed in neighboring neuronal populations. These include a hypertrophy of basket cell axonal processes and changes in the distribution of climbing fiber-Purkinje cell synapses. These changes all distinguish ET from normal control brains. Initial studies further indicate that the profile (i.e., constellation) of these changes may separate ET from other diseases of the cerebellum, thereby serving as a disease signature. With the discovery of these changes, a new model of ET has arisen, which posits that it may be a neurodegenerative disorder centered in the cerebellar cortex. These newly emerging neuropathological studies pave the way for anatomically focused, hypothesis-driven, molecular mechanistic studies of disease pathogenesis.

  7. Characterization of human MMTV-like (HML) elements similar to a sequence that was highly expressed in a human breast cancer: further definition of the HML-6 group.

    Science.gov (United States)

    Yin, H; Medstrand, P; Kristofferson, A; Dietrich, U; Aman, P; Blomberg, J

    1999-03-30

    Previously, we found a retroviral sequence, HML-6.2BC1, to be expressed at high levels in a multifocal ductal breast cancer from a 41-year-old woman who also developed ovarian carcinoma. The sequence of a human genomic clone (HML-6.28) selected by high-stringency hybridization with HML-6.2BC1 is reported here. It was 99% identical to HML-6.2BC1 and gave the same restriction fragments as total DNA. HML-6.28 is a 4.7-kb provirus with a 5'LTR, truncated in RT. Data from two similar genomic clones and sequences found in GenBank are also reported. Overlaps between them gave a rather complete picture of the HML-6.2BC1-like human endogenous retroviral elements. Work with somatic cell hybrids and FISH localized HML-6.28 to chromosome 6, band p21, close to the MHC region. The causal role of HML-6.28 in breast cancer remains unclear. Nevertheless, the ca. 20 Myr old HML-6 sequences enabled the definition of common and unique features of type A, B, and D (ABD) retroviruses. In Gag, HML-6 has no intervening sequences between matrix and capsid proteins, unlike extant exogenous ABD viruses, possibly an ancestral feature. Alignment of the dUTPase showed it to be present in all ABD viruses, but gave a phylogenetic tree different from trees made from other ABD genes, indicating a distinct phylogeny of dUTPase. A conserved 24-mer sequence in the amino terminus of some ABD envelope genes suggested a conserved function. Copyright 1999 Academic Press.

  8. The G protein-coupled receptor subset of the dog genome is more similar to that in humans than rodents

    OpenAIRE

    Schiöth Helgi B; Foord Steven M; Fredriksson Robert; Haitina Tatjana; Gloriam David E

    2009-01-01

    Abstract Background The dog is an important model organism and it is considered to be closer to humans than rodents regarding metabolism and responses to drugs. The close relationship between humans and dogs over many centuries has lead to the diversity of the canine species, important genetic discoveries and an appreciation of the effects of old age in another species. The superfamily of G protein-coupled receptors (GPCRs) is one of the largest gene families in most mammals and the most expl...

  9. The relative use of proximity, shape similarity, and orientation as visual perceptual grouping cues in tufted capuchin monkeys (Cebus apella) and humans (Homo sapiens).

    Science.gov (United States)

    Spinozzi, Giovanna; De Lillo, Carlo; Truppa, Valentina; Castorina, Giulia

    2009-02-01

    Recent experimental results suggest that human and nonhuman primates differ in how they process visual information to assemble component parts into global shapes. To assess whether some of the observed differences in perceptual grouping could be accounted for by the prevalence of different grouping factors in different species, we carried out 2 experiments designed to evaluate the relative use of proximity, similarity of shape, and orientation as grouping cues in humans (Homo sapiens) and capuchin monkeys (Cebus apella). Both species showed similarly high levels of accuracy using proximity as a cue. Moreover, for both species, grouping by orientation similarity produced a lower level of performance than grouping by proximity. Differences emerged with respect to the use of shape similarity as a cue. In humans, grouping by shape similarity also proved less effective than grouping by proximity but the same was not observed in capuchins. These results suggest that there may be subtle differences between humans and capuchin monkeys in the weighting assigned to different grouping cues that may affect the way in which they combine local features into global shapes. Copyright 2009 APA, all rights reserved.

  10. Development of a systematic method to assess similarity between nanomaterials for human hazard evaluation purposes - lessons learnt.

    NARCIS (Netherlands)

    Vdz Park, Margriet; Catalán, Julia; Ferraz, Natalia; Cabellos, Joan; Vanhauten, Ralph; Vázquez-Campos, Socorro; Janer, Gemma

    2018-01-01

    Within the EU FP-7 GUIDEnano project, a methodology was developed to systematically quantify the similarity between a nanomaterial (NM) that has been tested in toxicity studies and the NM for which risk needs to be evaluated, for the purpose of extrapolating toxicity data between the two materials.

  11. Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages : similarities and differences

    NARCIS (Netherlands)

    Martinez, Fernando O.; Helming, Laura; Milde, Ronny; Varin, Audrey; Melgert, Barbro N.; Draijer, Christina; Thomas, Benjamin; Fabbri, Marco; Crawshaw, Anjali; Ho, Ling Pei; Ten Hacken, Nick H.; Jimenez, Viviana Cobos; Kootstra, Neeltje A.; Hamann, Jorg; Greaves, David R.; Locati, Massimo; Mantovani, Alberto; Gordon, Siamon

    2013-01-01

    The molecular repertoire of macrophages in health and disease can provide novel biomarkers for diagnosis, prognosis, and treatment. Th2-IL-4-activated macrophages (M2) have been associated with important diseases in mice, yet no specific markers are available for their detection in human tissues.

  12. Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages: similarities and differences

    NARCIS (Netherlands)

    Martinez, Fernando O.; Helming, Laura; Milde, Ronny; Varin, Audrey; Melgert, Barbro N.; Draijer, Christina; Thomas, Benjamin; Fabbri, Marco; Crawshaw, Anjali; Ho, Ling Pei; ten Hacken, Nick H.; Cobos Jiménez, Viviana; Kootstra, Neeltje A.; Hamann, Jörg; Greaves, David R.; Locati, Massimo; Mantovani, Alberto; Gordon, Siamon

    2013-01-01

    The molecular repertoire of macrophages in health and disease can provide novel biomarkers for diagnosis, prognosis, and treatment. Th2-IL-4-activated macrophages (M2) have been associated with important diseases in mice, yet no specific markers are available for their detection in human tissues.

  13. User involvement in the design of human-computer interactions: some similarities and differences between design approaches

    NARCIS (Netherlands)

    Bekker, M.M.; Long, J.B.

    1998-01-01

    This paper presents a general review of user involvement in the design of human-computer interactions, as advocated by a selection of different approaches to design. The selection comprises User-Centred Design, Participatory Design, Socio-Technical Design, Soft Systems Methodology, and Joint

  14. Free-form image registration of human cochlear μCT data using skeleton similarity as anatomical prior

    DEFF Research Database (Denmark)

    Kjer, Hans Martin; Fagertun, Jens; Vera, Sergio

    2016-01-01

    Better understanding of the anatomical variability of the human cochlear is important for the design and function of Cochlear Implants. Proper non-rigid alignment of high-resolution cochlear μCT data is a challenge for the typical cubic B-spline registration model. In this paper we study one way ...

  15. Similar efficacy of human banked milk and bovine colostrum to decrease incidence of necrotizing enterocolitis in preterm piglets

    DEFF Research Database (Denmark)

    Jensen, Michael L.; Sangild, Per Torp; Lykke, Mikkel

    2013-01-01

    Preterm birth and formula feeding predispose to necrotizing enterocolitis (NEC) in infants. As mother's milk is often absent following preterm delivery, infant formula (IF) and human donor milk (HM) are frequently used as alternatives. We have previously shown that porcine and bovine colostrum (BC...

  16. Perinatal administration of aromatase inhibitors in rodents as animal models of human male homosexuality: similarities and differences.

    Science.gov (United States)

    Olvera-Hernández, Sandra; Fernández-Guasti, Alonso

    2015-01-01

    In this chapter we briefly review the evidence supporting the existence of biological influences on sexual orientation. We focus on basic research studies that have affected the estrogen synthesis during the critical periods of brain sexual differentiation in male rat offspring with the use of aromatase inhibitors, such as 1,4,6-androstatriene-3,17 (ATD) and letrozole. The results after prenatal and/or postnatal treatment with ATD reveal that these animals, when adults, show female sexual responses, such as lordosis or proceptive behaviors, but retain their ability to display male sexual activity with a receptive female. Interestingly, the preference and sexual behavior of these rats vary depending upon the circadian rhythm.Recently, we have established that the treatment with low doses of letrozole during the second half of pregnancy produces male rat offspring, that when adults spend more time in the company of a sexually active male than with a receptive female in a preference test. In addition, they display female sexual behavior when forced to interact with a sexually experienced male and some typical male sexual behavior when faced with a sexually receptive female. Interestingly, these males displayed both sexual behavior patterns spontaneously, i.e., in absence of exogenous steroid hormone treatment. Most of these features correspond with those found in human male homosexuals; however, the "bisexual" behavior shown by the letrozole-treated rats may be related to a particular human population. All these data, taken together, permit to propose letrozole prenatal treatment as a suitable animal model to study human male homosexuality and reinforce the hypothesis that human sexual orientation is underlied by changes in the endocrine milieu during early development.

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

    Directory of Open Access Journals (Sweden)

    Christel Logez

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

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

    Science.gov (United States)

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

    2014-01-01

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

  19. Intraoperative neuropathology of glioma recurrence: cell detection and classification

    Science.gov (United States)

    Abas, Fazly S.; Gokozan, Hamza N.; Goksel, Behiye; Otero, Jose J.; Gurcan, Metin N.

    2016-03-01

    Intraoperative neuropathology of glioma recurrence represents significant visual challenges to pathologists as they carry significant clinical implications. For example, rendering a diagnosis of recurrent glioma can help the surgeon decide to perform more aggressive resection if surgically appropriate. In addition, the success of recent clinical trials for intraoperative administration of therapies, such as inoculation with oncolytic viruses, may suggest that refinement of the intraoperative diagnosis during neurosurgery is an emerging need for pathologists. Typically, these diagnoses require rapid/STAT processing lasting only 20-30 minutes after receipt from neurosurgery. In this relatively short time frame, only dyes, such as hematoxylin and eosin (H and E), can be implemented. The visual challenge lies in the fact that these patients have undergone chemotherapy and radiation, both of which induce cytological atypia in astrocytes, and pathologists are unable to implement helpful biomarkers in their diagnoses. Therefore, there is a need to help pathologists differentiate between astrocytes that are cytologically atypical due to treatment versus infiltrating, recurrent, neoplastic astrocytes. This study focuses on classification of neoplastic versus non-neoplastic astrocytes with the long term goal of providing a better neuropathological computer-aided consultation via classification of cells into reactive gliosis versus recurrent glioma. We present a method to detect cells in H and E stained digitized slides of intraoperative cytologic preparations. The method uses a combination of the `value' component of the HSV color space and `b*' component of the CIE L*a*b* color space to create an enhanced image that suppresses the background while revealing cells on an image. A composite image is formed based on the morphological closing of the hue-luminance combined image. Geometrical and textural features extracted from Discrete Wavelet Frames and combined to classify

  20. 4D flow mri post-processing strategies for neuropathologies

    Science.gov (United States)

    Schrauben, Eric Mathew

    4D flow MRI allows for the measurement of a dynamic 3D velocity vector field. Blood flow velocities in large vascular territories can be qualitatively visualized with the added benefit of quantitative probing. Within cranial pathologies theorized to have vascular-based contributions or effects, 4D flow MRI provides a unique platform for comprehensive assessment of hemodynamic parameters. Targeted blood flow derived measurements, such as flow rate, pulsatility, retrograde flow, or wall shear stress may provide insight into the onset or characterization of more complex neuropathologies. Therefore, the thorough assessment of each parameter within the context of a given disease has important medical implications. Not surprisingly, the last decade has seen rapid growth in the use of 4D flow MRI. Data acquisition sequences are available to researchers on all major scanner platforms. However, the use has been limited mostly to small research trials. One major reason that has hindered the more widespread use and application in larger clinical trials is the complexity of the post-processing tasks and the lack of adequate tools for these tasks. Post-processing of 4D flow MRI must be semi-automated, fast, user-independent, robust, and reliably consistent for use in a clinical setting, within large patient studies, or across a multicenter trial. Development of proper post-processing methods coupled with systematic investigation in normal and patient populations pushes 4D flow MRI closer to clinical realization while elucidating potential underlying neuropathological origins. Within this framework, the work in this thesis assesses venous flow reproducibility and internal consistency in a healthy population. A preliminary analysis of venous flow parameters in healthy controls and multiple sclerosis patients is performed in a large study employing 4D flow MRI. These studies are performed in the context of the chronic cerebrospinal venous insufficiency hypothesis. Additionally, a

  1. Mitochondrial damage and cytoskeleton reorganization in human dermal fibroblasts exposed to artificial visible light similar to screen-emitted light.

    Science.gov (United States)

    Rascalou, Adeline; Lamartine, Jérôme; Poydenot, Pauline; Demarne, Frédéric; Bechetoille, Nicolas

    2018-05-05

    Artificial visible light is everywhere in modern life. Social communication confronts us with screens of all kinds, and their use is on the rise. We are therefore increasingly exposed to artificial visible light, the effects of which on skin are poorly known. The purpose of this study was to model the artificial visible light emitted by electronic devices and assess its effect on normal human fibroblasts. The spectral irradiance emitted by electronic devices was optically measured and equipment was developed to accurately reproduce such artificial visible light. Effects on normal human fibroblasts were analyzed on human genome microarray-based gene expression analysis. At cellular level, visualization and image analysis were performed on the mitochondrial network and F-actin cytoskeleton. Cell proliferation, ATP release and type I procollagen secretion were also measured. We developed a device consisting of 36 LEDs simultaneously emitting blue, green and red light at distinct wavelengths (450 nm, 525 nm and 625 nm) with narrow spectra and equivalent radiant power for the three colors. A dose of 99 J/cm 2 artificial visible light was selected so as not to induce cell mortality following exposure. Microarray analysis revealed 2984 light-modulated transcripts. Functional annotation of light-responsive genes revealed several enriched functions including, amongst others, the "mitochondria" and "integrin signaling" categories. Selected results were confirmed by real-time quantitative PCR, analyzing 24 genes representing these two categories. Analysis of micro-patterned culture plates showed marked fragmentation of the mitochondrial network and disorganization of the F-actin cytoskeleton following exposure. Functionally, there was considerable impairment of cell growth and spread, ATP release and type I procollagen secretion in exposed fibroblasts. Artificial visible light induces drastic molecular and cellular changes in normal human fibroblasts. This may impede

  2. Cultured human foreskin fibroblasts produce a factor that stimulates their growth with properties similar to basic fibroblast growth factor

    International Nuclear Information System (INIS)

    Story, M.T.

    1989-01-01

    To determine if fibroblasts could be a source of fibroblast growth factor (FGF) in tissue, cells were initiated in culture from newborn human foreskin. Fibroblast cell lysates promoted radiolabeled thymidine uptake by cultured quiescent fibroblasts. Seventy-nine percent of the growth-promoting activity of lysates was recovered from heparin-Sepharose. The heparin-binding growth factor reacted on immunoblots with antiserum to human placenta-derived basic FGF and competed with iodinated basic FGF for binding to antiserum to (1-24)bFGF synthetic peptide. To confirm that fibroblasts were the source of the growth factor, cell lysates were prepared from cells incubated with radiolabeled methionine. Heparin affinity purified material was immunoprecipitated with basic FGF antiserum and electrophoresed. Radiolabeled material was detected on gel autoradiographs in the same molecular weight region as authentic iodinated basic FGF. The findings are consistant with the notion that cultured fibroblasts express basic FGF. As these cells also respond to the mitogen, it is possible that the regulation of their growth is under autocrine control. Fibroblasts may be an important source of the growth factor in tissue

  3. IntNetLncSim: an integrative network analysis method to infer human lncRNA functional similarity.

    Science.gov (United States)

    Cheng, Liang; Shi, Hongbo; Wang, Zhenzhen; Hu, Yang; Yang, Haixiu; Zhou, Chen; Sun, Jie; Zhou, Meng

    2016-07-26

    Increasing evidence indicated that long non-coding RNAs (lncRNAs) were involved in various biological processes and complex diseases by communicating with mRNAs/miRNAs each other. Exploiting interactions between lncRNAs and mRNA/miRNAs to lncRNA functional similarity (LFS) is an effective method to explore function of lncRNAs and predict novel lncRNA-disease associations. In this article, we proposed an integrative framework, IntNetLncSim, to infer LFS by modeling the information flow in an integrated network that comprises both lncRNA-related transcriptional and post-transcriptional information. The performance of IntNetLncSim was evaluated by investigating the relationship of LFS with the similarity of lncRNA-related mRNA sets (LmRSets) and miRNA sets (LmiRSets). As a result, LFS by IntNetLncSim was significant positively correlated with the LmRSet (Pearson correlation γ2=0.8424) and LmiRSet (Pearson correlation γ2=0.2601). Particularly, the performance of IntNetLncSim is superior to several previous methods. In the case of applying the LFS to identify novel lncRNA-disease relationships, we achieved an area under the ROC curve (0.7300) in experimentally verified lncRNA-disease associations based on leave-one-out cross-validation. Furthermore, highly-ranked lncRNA-disease associations confirmed by literature mining demonstrated the excellent performance of IntNetLncSim. Finally, a web-accessible system was provided for querying LFS and potential lncRNA-disease relationships: http://www.bio-bigdata.com/IntNetLncSim.

  4. Impact of Cytokines and Chemokines on Alzheimer's Disease Neuropathological Hallmarks.

    Science.gov (United States)

    Domingues, Catarina; da Cruz E Silva, Odete A B; Henriques, Ana Gabriela

    2017-01-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder, neuropathologically characterized by aggregates of β-amyloid peptides, which deposit as senile plaques, and of TAU protein, which forms neurofibrillary tangles. It is now widely accepted that neuroinflammation is implicated in AD pathogenesis. Indeed, inflammatory mediators, such as cytokines and chemokines (chemotactic cytokines) can impact on the Alzheimer´s amyloid precursor protein by affecting its expression levels and amyloidogenic processing and/or β -amyloid aggregation. Additionally, cytokines and chemokines can influence kinases' activities, leading to abnormal TAU phosphorylation. To date there is no cure for AD, but several therapeutic strategies have been directed to prevent neuroinflammation. Anti-inflammatory, but also anti-amyloidogenic compounds, such as flavonoids were shown to favourably modulate some pathological events associated with neurodegeneration. This review focuses on the role of cytokines and chemokines in AD-associated pathologies, and summarizes the potential anti-inflammatory therapeutic approaches aimed at preventing or slowing down disease progression. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Review: Hippocampal sclerosis in epilepsy: a neuropathology review

    Science.gov (United States)

    Thom, Maria

    2014-01-01

    Hippocampal sclerosis (HS) is a common pathology encountered in mesial temporal lobe epilepsy (MTLE) as well as other epilepsy syndromes and in both surgical and post-mortem practice. The 2013 International League Against Epilepsy (ILAE) classification segregates HS into typical (type 1) and atypical (type 2 and 3) groups, based on the histological patterns of subfield neuronal loss and gliosis. In addition, granule cell reorganization and alterations of interneuronal populations, neuropeptide fibre networks and mossy fibre sprouting are distinctive features of HS associated with epilepsies; they can be useful diagnostic aids to discriminate from other causes of HS, as well as highlighting potential mechanisms of hippocampal epileptogenesis. The cause of HS remains elusive and may be multifactorial; the contribution of febrile seizures, genetic susceptibility, inflammatory and neurodevelopmental factors are discussed. Post-mortem based research in HS, as an addition to studies on surgical samples, has the added advantage of enabling the study of the wider network changes associated with HS, the long-term effects of epilepsy on the pathology and associated comorbidities. It is likely that HS is heterogeneous in aspects of its cause, epileptogenetic mechanisms, network alterations and response to medical and surgical treatments. Future neuropathological studies will contribute to better recognition and understanding of these clinical and patho-aetiological subtypes of HS. PMID:24762203

  6. Cytotoxic and Apoptotic Effect of Structurally Similar Flavonoids on Parental and Drug-Resistant Cells of a Human Cervical Carcinoma

    Directory of Open Access Journals (Sweden)

    Ksenija Durgo

    2009-01-01

    Full Text Available Flavonoids are phytochemicals characterized by a wide range of biological activities, including antioxidant activity, the ability to modulate enzyme or cell receptor activity patterns, and to interfere with essential biochemical pathways. Using HeLa cells of a human cervical carcinoma, and their drug-resistant HeLa CK subline, the effects of three structurally related flavonoids (quercetin, fisetin and luteolin have been examined, in terms of their: (i cytotoxicity, (ii influence on intracellular glutathione (GSH level, (iii influence on glutathione S-transferase (GST activity, and (iv influence on the expression of apoptosis-related genes (PARP, Bcl-2, survivin. Fisetin was more toxic to resistant HeLa CK cell line than to parental cell line, causing decreased expression of survivin in the same cell line. Concentrations of 5 μM of the examined flavonoids caused PARP degradation in parental cell line, leading HeLa cell line into apoptotic cell death. The same event was not determined in the resistant cell line. Fisetin and luteolin induce glutathione and GST in the resistant cell line, pointing to complex cellular effects which could be responsible for higher sensitivity of the resistant cell line in comparison with the parental cell line. Prooxidative nature of the investigated flavonoids was not detected, so free radical formation is not responsible for the induction of GSH, GST and proapoptotic enzymes.

  7. Detection of single amino acid mutation in human breast cancer by disordered plasmonic self-similar chain

    KAUST Repository

    Coluccio, M. L.

    2015-09-04

    Control of the architecture and electromagnetic behavior of nanostructures offers the possibility of designing and fabricating sensors that, owing to their intrinsic behavior, provide solutions to new problems in various fields. We show detection of peptides in multicomponent mixtures derived from human samples for early diagnosis of breast cancer. The architecture of sensors is based on a matrix array where pixels constitute a plasmonic device showing a strong electric field enhancement localized in an area of a few square nanometers. The method allows detection of single point mutations in peptides composing the BRCA1 protein. The sensitivity demonstrated falls in the picomolar (10−12 M) range. The success of this approach is a result of accurate design and fabrication control. The residual roughness introduced by fabrication was taken into account in optical modeling and was a further contributing factor in plasmon localization, increasing the sensitivity and selectivity of the sensors. This methodology developed for breast cancer detection can be considered a general strategy that is applicable to various pathologies and other chemical analytical cases where complex mixtures have to be resolved in their constitutive components.

  8. Detection of single amino acid mutation in human breast cancer by disordered plasmonic self-similar chain

    KAUST Repository

    Coluccio, M. L.; Gentile, F.; Das, Gobind; Nicastri, A.; Perri, A. M.; Candeloro, P.; Perozziello, G.; Proietti Zaccaria, R.; Gongora, J. S. Totero; Alrasheed, Salma; Fratalocchi, Andrea; Limongi, Tania; Cuda, G.; Di Fabrizio, Enzo M.

    2015-01-01

    Control of the architecture and electromagnetic behavior of nanostructures offers the possibility of designing and fabricating sensors that, owing to their intrinsic behavior, provide solutions to new problems in various fields. We show detection of peptides in multicomponent mixtures derived from human samples for early diagnosis of breast cancer. The architecture of sensors is based on a matrix array where pixels constitute a plasmonic device showing a strong electric field enhancement localized in an area of a few square nanometers. The method allows detection of single point mutations in peptides composing the BRCA1 protein. The sensitivity demonstrated falls in the picomolar (10−12 M) range. The success of this approach is a result of accurate design and fabrication control. The residual roughness introduced by fabrication was taken into account in optical modeling and was a further contributing factor in plasmon localization, increasing the sensitivity and selectivity of the sensors. This methodology developed for breast cancer detection can be considered a general strategy that is applicable to various pathologies and other chemical analytical cases where complex mixtures have to be resolved in their constitutive components.

  9. Potential teratogenicity of methimazole: exposure of zebrafish embryos to methimazole causes similar developmental anomalies to human methimazole embryopathy.

    Science.gov (United States)

    Komoike, Yuta; Matsuoka, Masato; Kosaki, Kenjiro

    2013-06-01

    While methimazole (MMI) is widely used in the therapy for hyperthyroidism, several groups have reported that maternal exposure to MMI results in a variety of congenital anomalies, including choanal and esophageal atresia, iridic and retinal coloboma, and delayed neurodevelopment. Thus, adverse effects of maternal exposure to MMI on fetal development have long been suggested; however, direct evidence for the teratogenicity of MMI has not been presented. Therefore, we studied the effects of MMI on early development by using zebrafish as a model organism. The fertilized eggs of zebrafish were collected immediately after spawning and grown in egg culture water containing MMI at various concentrations. External observation of the embryos revealed that exposure to high concentrations of MMI resulted in loss of pigmentation, hypoplastic hindbrain, turbid tissue in the forebrain, swelling of the notochord, and curly trunk. Furthermore, these effects occurred in a dose-dependent manner. Precise observation of the serial cross-sections of MMI-exposed embryos elucidated delayed development and hypoplasia of the whole brain and spinal cord, narrowing of the pharynx and esophagus, severe disruption of the retina, and aberrant structure of the notochord. These neuronal, pharyngeal, esophageal, and retinal anomalous morphologies have a direct analogy to the congenital anomalies observed in children exposed to MMI in utero. Here, we show the teratogenic effects of MMI on the development of zebrafish and provide the first experimental evidence for the connection between exposure to MMI and human MMI embryopathy. © 2013 Wiley Periodicals, Inc.

  10. MM2-thalamic Creutzfeldt-Jakob disease: neuropathological, biochemical and transmission studies identify a distinctive prion strain.

    Science.gov (United States)

    Moda, Fabio; Suardi, Silvia; Di Fede, Giuseppe; Indaco, Antonio; Limido, Lucia; Vimercati, Chiara; Ruggerone, Margherita; Campagnani, Ilaria; Langeveld, Jan; Terruzzi, Alessandro; Brambilla, Antonio; Zerbi, Pietro; Fociani, Paolo; Bishop, Matthew T; Will, Robert G; Manson, Jean C; Giaccone, Giorgio; Tagliavini, Fabrizio

    2012-09-01

    In Creutzfeldt-Jakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrP(Sc) ) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrP(Sc) and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrP(Sc) are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia. We observed two young patients with MM2-thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nucleus. Western blot analysis showed the presence of type 2A PrP(Sc) . Challenge of transgenic mice expressing 129MM human PrP showed that MM2-thalamic sporadic CJD (sCJD) was able to transmit the disease, at variance with MM2-cortical sCJD. The affected mice showed deposition of type 2A PrP(Sc) , a scenario that is unprecedented in this mouse line. These data indicate that MM2-thalamic sCJD is caused by a prion strain distinct from the other sCJD subtypes including the MM2-cortical form. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

  11. The handyman's brain: a neuroimaging meta-analysis describing the similarities and differences between grip type and pattern in humans.

    Science.gov (United States)

    King, M; Rauch, H G; Stein, D J; Brooks, S J

    2014-11-15

    Handgrip is a ubiquitous human movement that was critical in our evolution. However, the differences in brain activity between grip type (i.e. power or precision) and pattern (i.e. dynamic or static) are not fully understood. In order to address this, we performed Activation Likelihood Estimation (ALE) analysis between grip type and grip pattern using functional magnetic resonance imaging (fMRI) data. ALE provides a probabilistic summary of the BOLD response in hundreds of subjects, which is often beyond the scope of a single fMRI experiment. We collected data from 28 functional magnetic resonance data sets, which included a total of 398 male and female subjects. Using ALE, we analyzed the BOLD response during power, precision, static and dynamic grip in a range of forces and age in right handed healthy individuals without physical impairment, cardiovascular or neurological dysfunction using a variety of grip tools, feedback and experimental training. Power grip generates unique activation in the postcentral gyrus (areas 1 and 3b) and precision grip generates unique activation in the supplementary motor area (SMA, area 6) and precentral gyrus (area 4a). Dynamic handgrip generates unique activation in the precentral gyrus (area 4p) and SMA (area 6) and of particular interest, both dynamic and static grip share activation in the area 2 of the postcentral gyrus, an area implicated in the evolution of handgrip. According to effect size analysis, precision and dynamic grip generates stronger activity than power and static, respectively. Our study demonstrates specific differences between grip type and pattern. However, there was a large degree of overlap in the pre and postcentral gyrus, SMA and areas of the frontal-parietal-cerebellar network, which indicates that other mechanisms are potentially involved in regulating handgrip. Further, our study provides empirically based regions of interest, which can be downloaded here within, that can be used to more effectively

  12. First case of human babesiosis in Korea: detection and characterization of a novel type of Babesia sp. (KO1) similar to ovine babesia.

    Science.gov (United States)

    Kim, Jung-Yeon; Cho, Shin-Hyeong; Joo, Hyun-Na; Tsuji, Masayoshi; Cho, Sung-Ran; Park, Il-Joong; Chung, Gyung-Tae; Ju, Jung-Won; Cheun, Hyeng-Il; Lee, Hyeong-Woo; Lee, Young-Hee; Kim, Tong-Soo

    2007-06-01

    We report on the first case of human babesiosis in Korea. The intraerythrocytic parasite (KO1) in the patient's blood mainly appeared as paired pyriforms and ring forms; but Maltese cross forms were not seen, and the parasite showed morphological features consistent with those of the genus Babesia sensu stricto. The sequence of the 18S rRNA gene of KO1 was closely related to that of Babesia spp. isolated from sheep in China (similarity, 98%). The present study provides the first evidence of the presence of a hitherto unidentified, new type of Babesia parasite capable of infecting humans.

  13. Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: clinical, neuroanatomical and neuropathological features

    Science.gov (United States)

    Mahoney, Colin J.; Beck, Jon; Rohrer, Jonathan D.; Lashley, Tammaryn; Mok, Kin; Shakespeare, Tim; Yeatman, Tom; Warrington, Elizabeth K.; Schott, Jonathan M.; Fox, Nick C.; Rossor, Martin N.; Hardy, John; Collinge, John; Revesz, Tamas; Mead, Simon

    2012-01-01

    with C9ORF72 mutation from the frontotemporal lobar degeneration series identified histomorphological features consistent with either type A or B TAR DNA-binding protein-43 deposition; however, p62-positive (in excess of TAR DNA-binding protein-43 positive) neuronal cytoplasmic inclusions in hippocampus and cerebellum were a consistent feature of these cases, in contrast to the similar frequency of p62 and TAR DNA-binding protein-43 deposition in 53 control cases with frontotemporal lobar degeneration–TAR DNA-binding protein. These findings corroborate the clinical importance of the C9ORF72 mutation in frontotemporal lobar degeneration, delineate phenotypic and neuropathological features that could help to guide genetic testing, and suggest hypotheses for elucidating the neurobiology of a culprit subcortical network. PMID:22366791

  14. Neuropathological diagnoses and clinical correlates in older adults in Brazil: A cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Claudia K Suemoto

    2017-03-01

    Full Text Available Clinicopathological studies are important in determining the brain lesions underlying dementia. Although almost 60% of individuals with dementia live in developing countries, few clinicopathological studies focus on these individuals. We investigated the frequency of neurodegenerative and vascular-related neuropathological lesions in 1,092 Brazilian admixed older adults, their correlation with cognitive and neuropsychiatric symptoms, and the accuracy of dementia subtype diagnosis.In this cross-sectional study, we describe clinical and neuropathological variables related to cognitive impairment in 1,092 participants (mean age = 74 y, 49% male, 69% white, and mean education = 4 y. Cognitive function was investigated using the Clinical Dementia Rating (CDR and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE; neuropsychiatric symptoms were evaluated using the Neuropsychiatric Inventory (NPI. Associations between neuropathological lesions and cognitive impairment were investigated using ordinal logistic regression. We developed a neuropathological comorbidity (NPC score and compared it to CDR, IQCODE, and NPI scores. We also described and compared the frequency of neuropathological diagnosis to clinical diagnosis of dementia subtype. Forty-four percent of the sample met criteria for neuropathological diagnosis. Among these participants, 50% had neuropathological diagnoses of Alzheimer disease (AD, and 35% of vascular dementia (VaD. Neurofibrillary tangles (NFTs, hippocampal sclerosis, lacunar infarcts, hyaline atherosclerosis, siderocalcinosis, and Lewy body disease were independently associated with cognitive impairment. Higher NPC scores were associated with worse scores in the CDR sum of boxes (β = 1.33, 95% CI 1.20-1.46, IQCODE (β = 0.14, 95% CI 0.13-0.16, and NPI (β = 1.74, 95% CI = 1.33-2.16. Compared to neuropathological diagnoses, clinical diagnosis had high sensitivity to AD and high specificity to dementia with

  15. Neuropathological changes following experimental stereotactic irradiation. Progressive injuries of oligodendrocytes

    International Nuclear Information System (INIS)

    Ohtsuka, Takashi; Seiki, Yoshikatsu; Nakano, Jiro; Shibata, Iekado; Terao, Hideo

    1997-01-01

    This report describes the results of neuropathological examinations in 14 rabbit brains after 100 Gy of linear stereotactic irradiation. The tissue around the area of radiation necrosis was subjected to special examination. Fourteen rabbits were given a single dose of 100 Gy by a linear accelerator with a use of the 10 mm collimator. Animals were sacrificed serially after irradiation. Brains were removed and formalin treated paraffin sections were made. All sections were stained by H and E, GFAP and TUNEL (TdT-mediated dUTP-biotin nick end labeling method) stain. Pathological changes of vessels and neural tissue around the area of necrosis were examined. Three months after irradiation, TUNEL-positive oligodendrocytes were seen scattered in the white matter or the radiated field, and after 6 months, these changes extended around the radiating field, but vessels and neurons appeared to be intact. Two years after irradiation, massive necrosis had occurred in the radiated area. Thickness and fibrinoid degeneration of the vessel walls were evident in the area around the necrosis. These vessel changes were recognized in the zone of the 40 Gy radiated region. TUNEL-positive oligodendrocytes were also observed around the necrosis, and were scattered in the white matter and corpus callosum over the region of vascular changes. These findings suggested the following: In the later period after irradiation, oligodendrocytes in the peripheral zone of necrosis are damaged by ischemia and edema, which are caused by vascular changes. TUNEL-positive oligodendrocytes which exsisted in the white matter and corpus callosum distal to the radiated area may exhibit development of serial damage of oligodendrocytes in those regions. (author)

  16. Similar substrate specificity of cynomolgus monkey cytochrome P450 2C19 to reported human P450 2C counterpart enzymes by evaluation of 89 drug clearances.

    Science.gov (United States)

    Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-12-01

    Cynomolgus monkeys are used widely in preclinical studies as non-human primate species. The amino acid sequence of cynomolgus monkey cytochrome P450 (P450 or CYP) 2C19 is reportedly highly correlated to that of human CYP2C19 (92%) and CYP2C9 (93%). In the present study, 89 commercially available compounds were screened to find potential substrates for cynomolgus monkey CYP2C19. Of 89 drugs, 34 were metabolically depleted by cynomolgus monkey CYP2C19 with relatively high rates. Among them, 30 compounds have been reported as substrates or inhibitors of, either or both, human CYP2C19 and CYP2C9. Several compounds, including loratadine, showed high selectivity to cynomolgus monkey CYP2C19, and all of these have been reported as human CYP2C19 and/or CYP2C9 substrates. In addition, cynomolgus monkey CYP2C19 formed the same loratadine metabolite as human CYP2C19, descarboethoxyloratadine. These results suggest that cynomolgus monkey CYP2C19 is generally similar to human CYP2C19 and CYP2C9 in its substrate recognition functionality. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Wolves (Canis lupus) and Dogs (Canis familiaris) Differ in Following Human Gaze Into Distant Space But Respond Similar to Their Packmates’ Gaze

    Science.gov (United States)

    Werhahn, Geraldine; Virányi, Zsófia; Barrera, Gabriela; Sommese, Andrea; Range, Friederike

    2017-01-01

    Gaze following into distant space is defined as visual co-orientation with another individual’s head direction allowing the gaze follower to gain information on its environment. Human and nonhuman animals share this basic gaze following behavior, suggested to rely on a simple reflexive mechanism and believed to be an important prerequisite for complex forms of social cognition. Pet dogs differ from other species in that they follow only communicative human gaze clearly addressed to them. However, in an earlier experiment we showed that wolves follow human gaze into distant space. Here we set out to investigate whether domestication has affected gaze following in dogs by comparing pack-living dogs and wolves raised and kept under the same conditions. In Study 1 we found that in contrast to the wolves, these dogs did not follow minimally communicative human gaze into distant space in the same test paradigm. In the observational Study 2 we found that pack-living dogs and wolves, similarly vigilant to environmental stimuli, follow the spontaneous gaze of their conspecifics similarly often. Our findings suggest that domestication did not affect the gaze following ability of dogs itself. The results raise hypotheses about which other dog skills might have been altered through domestication that may have influenced their performance in Study 1. Because following human gaze in dogs might be influenced by special evolutionary as well as developmental adaptations to interactions with humans, we suggest that comparing dogs to other animal species might be more informative when done in intraspecific social contexts. PMID:27244538

  18. Wolves (Canis lupus) and dogs (Canis familiaris) differ in following human gaze into distant space but respond similar to their packmates' gaze.

    Science.gov (United States)

    Werhahn, Geraldine; Virányi, Zsófia; Barrera, Gabriela; Sommese, Andrea; Range, Friederike

    2016-08-01

    Gaze following into distant space is defined as visual co-orientation with another individual's head direction allowing the gaze follower to gain information on its environment. Human and nonhuman animals share this basic gaze following behavior, suggested to rely on a simple reflexive mechanism and believed to be an important prerequisite for complex forms of social cognition. Pet dogs differ from other species in that they follow only communicative human gaze clearly addressed to them. However, in an earlier experiment we showed that wolves follow human gaze into distant space. Here we set out to investigate whether domestication has affected gaze following in dogs by comparing pack-living dogs and wolves raised and kept under the same conditions. In Study 1 we found that in contrast to the wolves, these dogs did not follow minimally communicative human gaze into distant space in the same test paradigm. In the observational Study 2 we found that pack-living dogs and wolves, similarly vigilant to environmental stimuli, follow the spontaneous gaze of their conspecifics similarly often. Our findings suggest that domestication did not affect the gaze following ability of dogs itself. The results raise hypotheses about which other dog skills might have been altered through domestication that may have influenced their performance in Study 1. Because following human gaze in dogs might be influenced by special evolutionary as well as developmental adaptations to interactions with humans, we suggest that comparing dogs to other animal species might be more informative when done in intraspecific social contexts. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  19. "Wolves (Canis lupus) and dogs (Canis familiaris) differ in following human gaze into distant space but respond similar to their packmates' gaze": Correction to Werhahn et al. (2016).

    Science.gov (United States)

    2017-02-01

    Reports an error in "Wolves ( Canis lupus ) and dogs ( Canis familiaris ) differ in following human gaze into distant space but respond similar to their packmates' gaze" by Geraldine Werhahn, Zsófia Virányi, Gabriela Barrera, Andrea Sommese and Friederike Range ( Journal of Comparative Psychology , 2016[Aug], Vol 130[3], 288-298). In the article, the affiliations for the second and fifth authors should be Wolf Science Center, Ernstbrunn, Austria, and Comparative Cognition, Messerli Research Institute, University of Veterinary Medicine Vienna/ Medical University of Vienna/University of Vienna. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2016-26311-001.) Gaze following into distant space is defined as visual co-orientation with another individual's head direction allowing the gaze follower to gain information on its environment. Human and nonhuman animals share this basic gaze following behavior, suggested to rely on a simple reflexive mechanism and believed to be an important prerequisite for complex forms of social cognition. Pet dogs differ from other species in that they follow only communicative human gaze clearly addressed to them. However, in an earlier experiment we showed that wolves follow human gaze into distant space. Here we set out to investigate whether domestication has affected gaze following in dogs by comparing pack-living dogs and wolves raised and kept under the same conditions. In Study 1 we found that in contrast to the wolves, these dogs did not follow minimally communicative human gaze into distant space in the same test paradigm. In the observational Study 2 we found that pack-living dogs and wolves, similarly vigilant to environmental stimuli, follow the spontaneous gaze of their conspecifics similarly often. Our findings suggest that domestication did not affect the gaze following ability of dogs itself. The results raise hypotheses about which other dog skills

  20. Electron microscopy and in vitro deneddylation reveal similar architectures and biochemistry of isolated human and Flag-mouse COP9 signalosome complexes

    International Nuclear Information System (INIS)

    Rockel, Beate; Schmaler, Tilo; Huang, Xiaohua; Dubiel, Wolfgang

    2014-01-01

    Highlights: • Deneddylation rates of human erythrocyte and mouse fibroblast CSN are very similar. • 3D models of native human and mouse CSN reveal common architectures. • The cryo-structure of native mammalian CSN shows a horseshoe subunit arrangement. - Abstract: The COP9 signalosome (CSN) is a regulator of the ubiquitin (Ub) proteasome system (UPS). In the UPS, proteins are Ub-labeled for degradation by Ub ligases conferring substrate specificity. The CSN controls a large family of Ub ligases called cullin-RING ligases (CRLs), which ubiquitinate cell cycle regulators, transcription factors and DNA damage response proteins. The CSN possesses structural similarities with the 26S proteasome Lid complex and the translation initiation complex 3 (eIF3) indicating similar ancestry and function. Initial structures were obtained 14 years ago by 2D electron microscopy (EM). Recently, first 3D molecular models of the CSN were created on the basis of negative-stain EM and single-particle analysis, mostly with recombinant complexes. Here, we compare deneddylating activity and structural features of CSN complexes purified in an elaborate procedure from human erythrocytes and efficiently pulled down from mouse Flag-CSN2 B8 fibroblasts. In an in vitro deneddylation assay both the human and the mouse CSN complexes deneddylated Nedd8-Cul1 with comparable rates. 3D structural models of the erythrocyte CSN as well as of the mouse Flag-CSN were generated by negative stain EM and by cryo-EM. Both complexes show a central U-shaped segment from which several arms emanate. This structure, called the horseshoe, is formed by the PCI domain subunits. CSN5 and CSN6 point away from the horseshoe. Compared to 3D models of negatively stained CSN complexes, densities assigned to CSN2 and CSN4 are better defined in the cryo-map. Because biochemical and structural results obtained with CSN complexes isolated from human erythrocytes and purified by Flag-CSN pulldown from mouse B8 fibroblasts

  1. Electron microscopy and in vitro deneddylation reveal similar architectures and biochemistry of isolated human and Flag-mouse COP9 signalosome complexes

    Energy Technology Data Exchange (ETDEWEB)

    Rockel, Beate [Department of Molecular Structural Biology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried (Germany); Schmaler, Tilo; Huang, Xiaohua [Division of Molecular Biology, Department of General, Visceral, Vascular and Thoracic Surgery, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin (Germany); Dubiel, Wolfgang, E-mail: Wolfgang.dubiel@charite.de [Division of Molecular Biology, Department of General, Visceral, Vascular and Thoracic Surgery, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin (Germany)

    2014-07-25

    Highlights: • Deneddylation rates of human erythrocyte and mouse fibroblast CSN are very similar. • 3D models of native human and mouse CSN reveal common architectures. • The cryo-structure of native mammalian CSN shows a horseshoe subunit arrangement. - Abstract: The COP9 signalosome (CSN) is a regulator of the ubiquitin (Ub) proteasome system (UPS). In the UPS, proteins are Ub-labeled for degradation by Ub ligases conferring substrate specificity. The CSN controls a large family of Ub ligases called cullin-RING ligases (CRLs), which ubiquitinate cell cycle regulators, transcription factors and DNA damage response proteins. The CSN possesses structural similarities with the 26S proteasome Lid complex and the translation initiation complex 3 (eIF3) indicating similar ancestry and function. Initial structures were obtained 14 years ago by 2D electron microscopy (EM). Recently, first 3D molecular models of the CSN were created on the basis of negative-stain EM and single-particle analysis, mostly with recombinant complexes. Here, we compare deneddylating activity and structural features of CSN complexes purified in an elaborate procedure from human erythrocytes and efficiently pulled down from mouse Flag-CSN2 B8 fibroblasts. In an in vitro deneddylation assay both the human and the mouse CSN complexes deneddylated Nedd8-Cul1 with comparable rates. 3D structural models of the erythrocyte CSN as well as of the mouse Flag-CSN were generated by negative stain EM and by cryo-EM. Both complexes show a central U-shaped segment from which several arms emanate. This structure, called the horseshoe, is formed by the PCI domain subunits. CSN5 and CSN6 point away from the horseshoe. Compared to 3D models of negatively stained CSN complexes, densities assigned to CSN2 and CSN4 are better defined in the cryo-map. Because biochemical and structural results obtained with CSN complexes isolated from human erythrocytes and purified by Flag-CSN pulldown from mouse B8 fibroblasts

  2. Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings.

    Science.gov (United States)

    Thom, Maria; Michalak, Zuzanna; Wright, Gabriella; Dawson, Timothy; Hilton, David; Joshi, Abhijit; Diehl, Beate; Koepp, Matthias; Lhatoo, Samden; Sander, Josemir W; Sisodiya, Sanjay M

    2016-08-01

    Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy. For classification of definite SUDEP, a post mortem (PM), including anatomical and toxicological examination, is mandatory to exclude other causes of death. We audited PM practice as well as the value of brain examination in SUDEP. We reviewed 145 PM reports in SUDEP cases from four UK neuropathology centres. Data were extracted for clinical epilepsy details, circumstances of death and neuropathological findings. Macroscopic brain abnormalities were identified in 52% of cases. Mild brain swelling was present in 28%, and microscopic pathologies relevant to cause or effect of seizures were seen in 89%. Examination based on whole fixed brains (76.6% of all PMs), and systematic regional sampling was associated with higher detection rates of underlying pathology (P detection of relevant pathology. Availability of full clinical epilepsy-related information at the time of PM could potentially further improve detection through targeted tissue sampling. Apart from confirmation of SUDEP, complete neuropathological examination contributes to evaluation of risk factors as well as helping to direct future research into underlying causes. © 2015 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

  3. Hippocampal volume as an index of Alzheimer neuropathology: findings from the Nun Study.

    Science.gov (United States)

    Gosche, K M; Mortimer, J A; Smith, C D; Markesbery, W R; Snowdon, D A

    2002-05-28

    To determine whether hippocampal volume is a sensitive and specific indicator of Alzheimer neuropathology, regardless of the presence or absence of cognitive and memory impairment. Postmortem MRI scans were obtained for the first 56 participants of the Nun Study who were scanned. The area under receiver operating characteristic curves, sensitivity, specificity, and positive and negative predictive values were used to assess the diagnostic accuracy of hippocampal volume in predicting fulfillment of Alzheimer neuropathologic criteria and differences in Braak staging. Hippocampal volume predicted fulfillment of neuropathologic criteria for AD for all 56 participants (p < 0.001): 24 sisters who were demented (p = 0.036); 32 sisters who remained nondemented (p < 0.001), 8 sisters who remained nondemented but had memory impairment (p < 0.001), and 24 sisters who were intact with regard to memory and cognition at the final examination prior to death (p = 0.003). In individuals who remained nondemented, hippocampal volume was a better indicator of AD neuropathology than a delayed memory measure. Among nondemented sisters, Braak stages III and VI were distinguishable from Braak stages II or lower (p = 0.001). Among cognitively intact individuals, those in Braak stage II could be distinguished from those in stage I or less (p = 0.025). Volumetric measures of the hippocampus may be useful in identifying nondemented individuals who satisfy neuropathologic criteria for AD as well as pathologic stages of AD that may be present decades before initial clinical expression.

  4. Neuropathologic comorbidity and cognitive impairment in the Nun and Honolulu-Asia Aging Studies.

    Science.gov (United States)

    White, Lon R; Edland, Steven D; Hemmy, Laura S; Montine, Kathleen S; Zarow, Chris; Sonnen, Joshua A; Uyehara-Lock, Jane H; Gelber, Rebecca P; Ross, G Webster; Petrovitch, Helen; Masaki, Kamal H; Lim, Kelvin O; Launer, Lenore J; Montine, Thomas J

    2016-03-15

    To examine frequencies and relationships of 5 common neuropathologic abnormalities identified at autopsy with late-life cognitive impairment and dementia in 2 different autopsy panels. The Nun Study (NS) and the Honolulu-Asia Aging Study (HAAS) are population-based investigations of brain aging that included repeated cognitive assessments and comprehensive brain autopsies. The neuropathologic abnormalities assessed were Alzheimer disease (AD) neuropathologic changes, neocortical Lewy bodies (LBs), hippocampal sclerosis, microinfarcts, and low brain weight. Associations with screening tests for cognitive impairment were examined. Neuropathologic abnormalities occurred at levels ranging from 9.7% to 43%, and were independently associated with cognitive impairment in both studies. Neocortical LBs and AD changes were more frequent among the predominantly Caucasian NS women, while microinfarcts were more common in the Japanese American HAAS men. Comorbidity was usual and very strongly associated with cognitive impairment. Apparent cognitive resilience (no cognitive impairment despite Braak stage V) was strongly associated with minimal or no comorbid abnormalities, with fewer neocortical AD lesions, and weakly with longer interval between final testing and autopsy. Total burden of comorbid neuropathologic abnormalities, rather than any single lesion type, was the most relevant determinant of cognitive impairment in both cohorts, often despite clinical diagnosis of only AD. These findings emphasize challenges to dementia pathogenesis and intervention research and to accurate diagnoses during life. © 2016 American Academy of Neurology.

  5. The semantic similarity ensemble

    Directory of Open Access Journals (Sweden)

    Andrea Ballatore

    2013-12-01

    Full Text Available Computational measures of semantic similarity between geographic terms provide valuable support across geographic information retrieval, data mining, and information integration. To date, a wide variety of approaches to geo-semantic similarity have been devised. A judgment of similarity is not intrinsically right or wrong, but obtains a certain degree of cognitive plausibility, depending on how closely it mimics human behavior. Thus selecting the most appropriate measure for a specific task is a significant challenge. To address this issue, we make an analogy between computational similarity measures and soliciting domain expert opinions, which incorporate a subjective set of beliefs, perceptions, hypotheses, and epistemic biases. Following this analogy, we define the semantic similarity ensemble (SSE as a composition of different similarity measures, acting as a panel of experts having to reach a decision on the semantic similarity of a set of geographic terms. The approach is evaluated in comparison to human judgments, and results indicate that an SSE performs better than the average of its parts. Although the best member tends to outperform the ensemble, all ensembles outperform the average performance of each ensemble's member. Hence, in contexts where the best measure is unknown, the ensemble provides a more cognitively plausible approach.

  6. The modulation of the motor resonance triggered by reach-to-grasp movements: No role of human physical similarity as conveyed by age.

    Science.gov (United States)

    Marino, Barbara F M; Ricciardelli, Paola

    2017-07-01

    The activation of the mirror-neuron circuit during the observation of motor acts is thought to be the basis of human capacity to read the intentions behind the behavior of others. Growing empirical evidence shows a different activation of the mirror-neuron resonance mechanism depending on how much the observer and the observed agent share their motor repertoires. Here, the possible modulatory effect of physical similarity between the observer and the agent was investigated in three studies. We used a visuo-motor priming task in which participants were asked to categorize manipulable and non-manipulable objects into natural or man-made kinds after having watched precision and power reach-to-grasp movements. Physical similarity was manipulated by presenting reach-to-grasp movements performed by the hands of actors of three different age ranges that are adults of the same age as the participants, children, and elderly. Faster responses were observed in trials where power grip movements were performed by the adults and precision grip movements were performed by the elderly (Main Study). This finding is not in keeping with the idea that physical similarity shapes the mirror-neuron resonance. Instead, it suggests an effect of the kinematic organization of the reach-to-grasp movements, which systematically changed with the actor age as revealed by a kinematic analysis. The differential effect played by adult and elderly actor primes was lost when static grasping hands (Control Study 1) and reach-to-grasp movements with uniform kinematic profiles (Control Study 2) were used. Therefore, we found preliminary evidence that mirror-neuron resonance is not shaped by physical similarity but by the kinematics of the observed action. This finding is novel as it suggests that human ability to read the intentions behind the behavior of others may benefit from a mere visual processing of spatiotemporal patterns.

  7. Molecular characterization of a Leishmania donovani cDNA clone with similarity to human 20S proteasome a-type subunit

    DEFF Research Database (Denmark)

    Christensen, C B; Jørgensen, L; Jensen, A T

    2000-01-01

    Using plasma from patients infected or previously infected with Leishmania donovanii, we isolated a L. donovanii cDNA clone with similarity to the proteasome a-type subunit from humans and other eukaryotes. The cDNA clone, designated LePa, was DNA sequenced and Northern blot analysis of L....... donovanii poly(A(+))mRNA indicated the isolation of a full length cDNA clone with a transcript size of 1.9 kb. The expressed recombinant LePa fusion protein induced proliferation of peripheral blood mononuclear cells in one out of seven patients who had suffered from visceral leishmaniasis. Plasma from 16...

  8. Characterization of cDNA for human tripeptidyl peptidase II: The N-terminal part of the enzyme is similar to subtilisin

    International Nuclear Information System (INIS)

    Tomkinson, B.; Jonsson, A-K

    1991-01-01

    Tripeptidyl peptidase II is a high molecular weight serine exopeptidase, which has been purified from rat liver and human erythrocytes. Four clones, representing 4453 bp, or 90% of the mRNA of the human enzyme, have been isolated from two different cDNA libraries. One clone, designated A2, was obtained after screening a human B-lymphocyte cDNA library with a degenerated oligonucleotide mixture. The B-lymphocyte cDNA library, obtained from human fibroblasts, were rescreened with a 147 bp fragment from the 5' part of the A2 clone, whereby three different overlapping cDNA clones could be isolated. The deduced amino acid sequence, 1196 amino acid residues, corresponding to the longest open rading frame of the assembled nucleotide sequence, was compared to sequences of current databases. This revealed a 56% similarity between the bacterial enzyme subtilisin and the N-terminal part of tripeptidyl peptidase II. The enzyme was found to be represented by two different mRNAs of 4.2 and 5.0 kilobases, respectively, which probably result from the utilziation of two different polyadenylation sites. Futhermore, cDNA corresponding to both the N-terminal and C-terminal part of tripeptidyl peptidase II hybridized with genomic DNA from mouse, horse, calf, and hen, even under fairly high stringency conditions, indicating that tripeptidyl peptidase II is highly conserved

  9. Frontotemporal dementia with severe thalamic involvement : a clinical and neuropathological study

    Directory of Open Access Journals (Sweden)

    Radanovic Márcia

    2003-01-01

    Full Text Available Frontotemporal dementia (FTD is the third-leading cause of cortical dementia after Alzheimer's disease and Lewy body dementia, and is characterized by a dementia where behavioral disturbances are prominent and appear early in the course of the disease. We report the case of a 58 year-old man affected by dementia with behavioral disturbances, in addition to rigid-hypokinetic and a lower motor neuron syndrome that were present at later stages of the illness. Neuroimaging studies showed frontotemporal atrophy. Neuropathological studies revealed intense thalamic neuronal loss and astrocytic gliosis, as well as moderate frontotemporal neuronal loss, astrocytosis and spongiform degeneration. Thalamic degeneration has previously been described among the wide group of neuropathological features of FTD. The aim of the present study is to show the clinical and neuropathological aspects of thalamic degeneration in FTD, along with its role in behavioral disturbances, a common finding in this condition.

  10. Lipopolysaccharide (LPS) stimulates fresh human monocytes to lyse actinomycin D-treated WEHI-164 target cells via increased secretion of a monokine similar to tumor necrosis factor

    International Nuclear Information System (INIS)

    Chen, A.R.; McKinnon, K.P.; Koren, H.S.

    1985-01-01

    The effects of lipopolysaccharide (LPS) on tumoricidal activity of human monocytes freshly isolated from peripheral blood were studied. Actinomycin D-treated WEHI-164 cells were used as targets because they are NK insensitive and are lysed rapidly by monocytes in 6-hr 51 Cr-release assays. Monocytes exhibited significant spontaneous activity without endotoxin. Monocytes either pretreated for 1 hr with LPS or assayed in the presence of LPS exhibited 100- to 1000-fold increased cytolytic activity. Cytolytic activity was heat labile and trypsin sensitive, and was recovered from Sepharose S-200 columns in a single peak with an apparent m.w. between 25,000 and 40,000. Actinomycin D or cycloheximide treatment of monocytes before the addition of LPS inhibited cytolytic monokine production. Cytolytic monokine activity was practically neutralized by specific rabbit antisera to human tumor necrosis factor (TNF). It was concluded that, although fresh human monocytes exhibit spontaneous tumoricidal activity, LPS is a potent activating agent. Its stimulatory effects depend on new transcription and translation and are mediated by enhanced secretion of a cytolytic monokine similar to TNF

  11. Masked-Volume-Wise PCA and "reference Logan" illustrate similar regional differences in kinetic behavior in human brain PET study using [11C]-PIB

    Directory of Open Access Journals (Sweden)

    Engler Henry

    2009-01-01

    Full Text Available Abstract Background Kinetic modeling using reference Logan is commonly used to analyze data obtained from dynamic Positron Emission Tomography (PET studies on patients with Alzheimer's disease (AD and healthy volunteers (HVs using amyloid imaging agent N-methyl [11C]2-(4'-methylaminophenyl-6-hydroxy-benzothiazole, [11C]-PIB. The aim of the present study was to explore whether results obtained using the newly introduced method, Masked Volume Wise Principal Component Analysis, MVW-PCA, were similar to the results obtained using reference Logan. Methods MVW-PCA and reference Logan were performed on dynamic PET images obtained from four Alzheimer's disease (AD patients on two occasions (baseline and follow-up and on four healthy volunteers (HVs. Regions of interest (ROIs of similar sizes were positioned in different parts of the brain in both AD patients and HVs where the difference between AD patients and HVs is largest. Signal-to-noise ratio (SNR and discrimination power (DP were calculated for images generated by the different methods and the results were compared both qualitatively and quantitatively. Results MVW-PCA generated images that illustrated similar regional binding patterns compared to reference Logan images and with slightly higher quality, enhanced contrast, improved SNR and DP, without being based on modeling assumptions. MVW-PCA also generated additional MVW-PC images by using the whole dataset, which illustrated regions with different and uncorrelated kinetic behaviors of the administered tracer. This additional information might improve the understanding of kinetic behavior of the administered tracer. Conclusion MVW-PCA is a potential multivariate method that without modeling assumptions generates high quality images, which illustrated similar regional changes compared to modeling methods such as reference Logan. In addition, MVW-PCA could be used as a new technique, applicable not only on dynamic human brain studies but also on

  12. Short-arm human centrifugation with 0.4g at eye and 0.75g at heart level provides similar cerebrovascular and cardiovascular responses to standing.

    Science.gov (United States)

    Goswami, Nandu; Bruner, Michelle; Xu, Da; Bareille, Marie-Pierre; Beck, Arnaud; Hinghofer-Szalkay, Helmut; Blaber, Andrew P

    2015-07-01

    Orthostatic intolerance continues to be a problem with astronauts upon return to Earth as a result of cerebral and cardiovascular adaptations to weightlessness. We tested the hypothesis that artificial gravity from a short-arm human centrifuge (SAHC) could provide cerebral and cardiovascular stimuli similar to upright posture and thereby serve as a suitable countermeasure. We compared cardiovascular and cerebrovascular responses before, during, and after exposure to hyper-G with that of standing in healthy young participants. The head was positioned such that the middle cerebral artery (MCA) was 0.46 m from the center of rotation. Two levels of hyper-G that provided 1g and 2g at foot level were investigated. Continuous blood pressure, heart rate, calf blood volume, MCA mean blood flow velocity (MFV) and end-tidal CO2 were measured. Blood pressure at the level of the MCA (BP-MCA) and MFV was reduced during stand and at 2g. The relationship between MFV and BP-MCA at 2g was different from supine and similar to standing, while 1g centrifugation was not different from supine. The cardiovascular system was also not different from supine at 1g but was similarly challenged in 2g compared to stand. Our data suggest that short-arm centrifugation 2g at the feet, with the head offset 0.5 m from the center, provides similar cardiovascular and cerebral responses to standing. This supports the hypothesis that passive 2g SAHC exposure at the feet could be used as a countermeasure for in-flight cardiovascular and cerebrovascular deconditioning.

  13. Fluoxetine Ameliorates Behavioral and Neuropathological Deficits in a Transgenic Model Mouse of α-synucleinopathy

    Science.gov (United States)

    Ubhi, Kiren; Inglis, Chandra; Mante, Michael; Patrick, Christina; Adame, Anthony; Spencer, Brian; Rockenstein, Edward; May, Verena; Winkler, Juergen; Masliah, Eliezer

    2013-01-01

    The term α-synucleinopathies refers to a group of age-related neurological disorders including Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA) that display an abnormal accumulation of alpha-synuclein (α-syn). In contrast to the neuronal α-syn accumulation observed in PD and DLB, MSA is characterized by a widespread oligodendrocytic α-syn accumulation. Transgenic mice expressing human α-syn under the oligodendrocyte-specific myelin basic protein promoter (MBP1-hαsyn tg mice) model many of the behavioral and neuropathological alterations observed in MSA. Fluoxetine, a selective serotonin reuptake inhibitor, has been shown to be protective in toxin-induced models of PD, however its effects in an in vivo transgenic model of α-synucleinopathy remain unclear. In this context, this study examined the effect of fluoxetine in the MBP1-hαsyn tg mice, a model of MSA. Fluoxetine adminstration ameliorated motor deficits in the MBP1-hαsyn tg mice, with a concomitant decrease in neurodegenerative pathology in the basal ganglia, neocortex and hippocampus. Fluoxetine adminstration also increased levels of the neurotrophic factors, GDNF (glial-derived neurotrophic factor) and BDNF (brain-derived neurotrophic factor) in the MBP1-hαsyn tg mice compared to vehicle-treated tg mice. This fluoxetine-induced increase in GDNF and BDNF protein levels was accompanied by activation of the ERK signaling pathway. The effects of fluoxetine adminstration on myelin and serotonin markers were also examined. Collectively these results indicate that fluoxetine may represent a novel therapeutic intervention for MSA and other neurodegenerative disorders. PMID:22281106

  14. Fluoxetine ameliorates behavioral and neuropathological deficits in a transgenic model mouse of α-synucleinopathy.

    Science.gov (United States)

    Ubhi, Kiren; Inglis, Chandra; Mante, Michael; Patrick, Christina; Adame, Anthony; Spencer, Brian; Rockenstein, Edward; May, Verena; Winkler, Juergen; Masliah, Eliezer

    2012-04-01

    The term α-synucleinopathies refers to a group of age-related neurological disorders including Parkinson's disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA) that display an abnormal accumulation of alpha-synuclein (α-syn). In contrast to the neuronal α-syn accumulation observed in PD and DLB, MSA is characterized by a widespread oligodendrocytic α-syn accumulation. Transgenic mice expressing human α-syn under the oligodendrocyte-specific myelin basic protein promoter (MBP1-hαsyn tg mice) model many of the behavioral and neuropathological alterations observed in MSA. Fluoxetine, a selective serotonin reuptake inhibitor, has been shown to be protective in toxin-induced models of PD, however its effects in an in vivo transgenic model of α-synucleinopathy remain unclear. In this context, this study examined the effect of fluoxetine in the MBP1-hαsyn tg mice, a model of MSA. Fluoxetine administration ameliorated motor deficits in the MBP1-hαsyn tg mice, with a concomitant decrease in neurodegenerative pathology in the basal ganglia, neocortex and hippocampus. Fluoxetine administration also increased levels of the neurotrophic factors, GDNF (glial-derived neurotrophic factor) and BDNF (brain-derived neurotrophic factor) in the MBP1-hαsyn tg mice compared to vehicle-treated tg mice. This fluoxetine-induced increase in GDNF and BDNF protein levels was accompanied by activation of the ERK signaling pathway. The effects of fluoxetine administration on myelin and serotonin markers were also examined. Collectively these results indicate that fluoxetine may represent a novel therapeutic intervention for MSA and other neurodegenerative disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Delayed recall, hippocampal volume and Alzheimer neuropathology: findings from the Nun Study.

    Science.gov (United States)

    Mortimer, J A; Gosche, K M; Riley, K P; Markesbery, W R; Snowdon, D A

    2004-02-10

    To examine the associations of hippocampal volume and the severity of neurofibrillary lesions determined at autopsy with delayed verbal recall performance evaluated an average of 1 year prior to death. Hippocampal volumes were computed using postmortem brain MRI from the first 56 scanned participants of the Nun Study. Quantitative neuropathologic studies included lesion counts, Braak staging, and determination of whether neuropathologic criteria for Alzheimer disease (AD) were met. Multiple regression was used to assess the association of hippocampal volume and neuropathologic lesions with the number of words (out of 10) recalled on the Consortium to Establish a Registry for Alzheimer's Disease Delayed Word Recall Test administered an average of 1 year prior to death. When entered separately, hippocampal volume, Braak stage, and the mean neurofibrillary tangle counts in the CA-1 region of the hippocampus and the subiculum were strongly associated with the number of words recalled after a delay, adjusting for age and education. When hippocampal volume was entered together with each neuropathologic index, only hippocampal volume retained a significant association with the delayed recall measure. The association between hippocampal volume and the number of words recalled was present in both demented and nondemented individuals as well as in those with and without substantial AD neurofibrillary pathology. The association of neurofibrillary tangles with delayed verbal recall may reflect associated hippocampal atrophy.

  16. Cerebral Dysfunctions Related to Perinatal Organic Damage: Clinical-Neuropathologic Correlations.

    Science.gov (United States)

    Towbin, Abraham

    1978-01-01

    Recent neuropathology studies identify hypoxia as the main cause of perinatal cerebral damage. Cerebral lesions present at birth, with transition to chronic scar lesions, are correlated to mental retardation, cerebral palsy, epilepsy, and minimal brain dysfunction. Gestation age and severity of hypoxic exposure essentially determine the cerebral…

  17. Relation of genomic variants for Alzheimer disease dementia to common neuropathologies.

    Science.gov (United States)

    Farfel, Jose M; Yu, Lei; Buchman, Aron S; Schneider, Julie A; De Jager, Philip L; Bennett, David A

    2016-08-02

    To investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies. This is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in large-scale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis. For each variant, multiple logistic regression was used to investigate its association with neuropathologic traits, adjusting for age, sex, and subpopulation structure. We also conducted power analyses to estimate the sample sizes required to detect genome-wide significance (p dementia variants are not likely to be detected for association with pathologic AD with a sample size in excess of the largest GWAS meta-analyses of AD dementia. Many recently discovered genomic variants for AD dementia are not associated with the pathology of AD. Some genomic variants for AD dementia appear to be associated with other common neuropathologies. © 2016 American Academy of Neurology.

  18. Chronic cerebral hypoperfusion-related neuropathologic changes and compromised cognitive status : Window of treatment

    NARCIS (Netherlands)

    Farkas, E; de Wilde, MC; Kiliaan, AJ; Luiten, PGM

    Neurodegenerative disorders, and dementia in particular, have been shown to have a cerebrovascular pathogenic component often in the form of reduced cerebral blood flow. The debate whether such a reduced brain perfusion is a primary trigger or a secondary symptom in the neuropathological progression

  19. Genome-wide association meta-analysis of neuropathologic features of Alzheimer's disease and related dementias.

    Directory of Open Access Journals (Sweden)

    Gary W Beecham

    2014-09-01

    Full Text Available Alzheimer's disease (AD and related dementias are a major public health challenge and present a therapeutic imperative for which we need additional insight into molecular pathogenesis. We performed a genome-wide association study and analysis of known genetic risk loci for AD dementia using neuropathologic data from 4,914 brain autopsies. Neuropathologic data were used to define clinico-pathologic AD dementia or controls, assess core neuropathologic features of AD (neuritic plaques, NPs; neurofibrillary tangles, NFTs, and evaluate commonly co-morbid neuropathologic changes: cerebral amyloid angiopathy (CAA, Lewy body disease (LBD, hippocampal sclerosis of the elderly (HS, and vascular brain injury (VBI. Genome-wide significance was observed for clinico-pathologic AD dementia, NPs, NFTs, CAA, and LBD with a number of variants in and around the apolipoprotein E gene (APOE. GalNAc transferase 7 (GALNT7, ATP-Binding Cassette, Sub-Family G (WHITE, Member 1 (ABCG1, and an intergenic region on chromosome 9 were associated with NP score; and Potassium Large Conductance Calcium-Activated Channel, Subfamily M, Beta Member 2 (KCNMB2 was strongly associated with HS. Twelve of the 21 non-APOE genetic risk loci for clinically-defined AD dementia were confirmed in our clinico-pathologic sample: CR1, BIN1, CLU, MS4A6A, PICALM, ABCA7, CD33, PTK2B, SORL1, MEF2C, ZCWPW1, and CASS4 with 9 of these 12 loci showing larger odds ratio in the clinico-pathologic sample. Correlation of effect sizes for risk of AD dementia with effect size for NFTs or NPs showed positive correlation, while those for risk of VBI showed a moderate negative correlation. The other co-morbid neuropathologic features showed only nominal association with the known AD loci. Our results discovered new genetic associations with specific neuropathologic features and aligned known genetic risk for AD dementia with specific neuropathologic changes in the largest brain autopsy study of AD and related

  20. Wound healing delays in α-Klotho-deficient mice that have skin appearance similar to that in aged humans - Study of delayed wound healing mechanism.

    Science.gov (United States)

    Yamauchi, Makoto; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Matsumoto, Yoshitaka; Yamashita, Ken; Kayama, Musashi; Sato, Noriyuki; Yotsuyanagi, Takatoshi

    2016-05-13

    Skin atrophy and delayed wound healing are observed in aged humans; however, the molecular mechanism are still elusive. The aim of this study was to analyze the molecular mechanisms of delayed wound healing by aging using α-Klotho-deficient (kl/kl) mice, which have phenotypes similar to those of aged humans. The kl/kl mice showed delayed wound healing and impaired granulation formation compared with those in wild-type (WT) mice. The skin graft experiments revealed that delayed wound healing depends on humoral factors, but not on kl/kl skin tissue. The mRNA expression levels of cytokines related to acute inflammation including IL-1β, IL-6 and TNF-α were higher in wound lesions of kl/kl mice compared with the levels in WT mice by RT-PCR analysis. LPS-induced TNF-α production model using spleen cells revealed that TNF-α production was significantly increased in the presence of FGF23. Thus, higher levels of FGF23 in kl/kl mouse may have a role to increase TNF-α production in would lesion independently of α-Klotho protein, and impair granulation formation and delay wound healing. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Of mice, birds, and men: the mouse ultrasonic song system has some features similar to humans and song-learning birds.

    Directory of Open Access Journals (Sweden)

    Gustavo Arriaga

    Full Text Available Humans and song-learning birds communicate acoustically using learned vocalizations. The characteristic features of this social communication behavior include vocal control by forebrain motor areas, a direct cortical projection to brainstem vocal motor neurons, and dependence on auditory feedback to develop and maintain learned vocalizations. These features have so far not been found in closely related primate and avian species that do not learn vocalizations. Male mice produce courtship ultrasonic vocalizations with acoustic features similar to songs of song-learning birds. However, it is assumed that mice lack a forebrain system for vocal modification and that their ultrasonic vocalizations are innate. Here we investigated the mouse song system and discovered that it includes a motor cortex region active during singing, that projects directly to brainstem vocal motor neurons and is necessary for keeping song more stereotyped and on pitch. We also discovered that male mice depend on auditory feedback to maintain some ultrasonic song features, and that sub-strains with differences in their songs can match each other's pitch when cross-housed under competitive social conditions. We conclude that male mice have some limited vocal modification abilities with at least some neuroanatomical features thought to be unique to humans and song-learning birds. To explain our findings, we propose a continuum hypothesis of vocal learning.

  2. GENE-07. MOLECULAR NEUROPATHOLOGY 2.0 - INCREASING DIAGNOSTIC ACCURACY IN PEDIATRIC NEUROONCOLOGY

    Science.gov (United States)

    Sturm, Dominik; Jones, David T.W.; Capper, David; Sahm, Felix; von Deimling, Andreas; Rutkoswki, Stefan; Warmuth-Metz, Monika; Bison, Brigitte; Gessi, Marco; Pietsch, Torsten; Pfister, Stefan M.

    2017-01-01

    Abstract The classification of central nervous system (CNS) tumors into clinically and biologically distinct entities and subgroups is challenging. Children and adolescents can be affected by >100 histological variants with very variable outcomes, some of which are exceedingly rare. The current WHO classification has introduced a number of novel molecular markers to aid routine neuropathological diagnostics, and DNA methylation profiling is emerging as a powerful tool to distinguish CNS tumor classes. The Molecular Neuropathology 2.0 study aims to integrate genome wide (epi-)genetic diagnostics with reference neuropathological assessment for all newly-diagnosed pediatric brain tumors in Germany. To date, >350 patients have been enrolled. A molecular diagnosis is established by epigenetic tumor classification through DNA methylation profiling and targeted panel sequencing of >130 genes to detect diagnostically and/or therapeutically useful DNA mutations, structural alterations, and fusion events. Results are aligned with the reference neuropathological diagnosis, and discrepant findings are discussed in a multi-disciplinary tumor board including reference neuroradiological evaluation. Ten FFPE sections as input material are sufficient to establish a molecular diagnosis in >95% of tumors. Alignment with reference pathology results in four broad categories: a) concordant classification (~77%), b) discrepant classification resolvable by tumor board discussion and/or additional data (~5%), c) discrepant classification without currently available options to resolve (~8%), and d) cases currently unclassifiable by molecular diagnostics (~10%). Discrepancies are enriched in certain histopathological entities, such as histological high grade gliomas with a molecularly low grade profile. Gene panel sequencing reveals predisposing germline events in ~10% of patients. Genome wide (epi-)genetic analyses add a valuable layer of information to routine neuropathological

  3. Similarities and differences between helminth parasites and cancer cell lines in shaping human monocytes: Insights into parallel mechanisms of immune evasion.

    Directory of Open Access Journals (Sweden)

    Prakash Babu Narasimhan

    2018-04-01

    Full Text Available A number of features at the host-parasite interface are reminiscent of those that are also observed at the host-tumor interface. Both cancer cells and parasites establish a tissue microenvironment that allows for immune evasion and may reflect functional alterations of various innate cells. Here, we investigated how the phenotype and function of human monocytes is altered by exposure to cancer cell lines and if these functional and phenotypic alterations parallel those induced by exposure to helminth parasites. Thus, human monocytes were exposed to three different cancer cell lines (breast, ovarian, or glioblastoma or to live microfilariae (mf of Brugia malayi-a causative agent of lymphatic filariasis. After 2 days of co-culture, monocytes exposed to cancer cell lines showed markedly upregulated expression of M1-associated (TNF-α, IL-1β, M2-associated (CCL13, CD206, Mreg-associated (IL-10, TGF-β, and angiogenesis associated (MMP9, VEGF genes. Similar to cancer cell lines, but less dramatically, mf altered the mRNA expression of IL-1β, CCL13, TGM2 and MMP9. When surface expression of the inhibitory ligands PDL1 and PDL2 was assessed, monocytes exposed to both cancer cell lines and to live mf significantly upregulated PDL1 and PDL2 expression. In contrast to exposure to mf, exposure to cancer cell lines increased the phagocytic ability of monocytes and reduced their ability to induce T cell proliferation and to expand Granzyme A+ CD8+ T cells. Our data suggest that despite the fact that helminth parasites and cancer cell lines are extraordinarily disparate, they share the ability to alter the phenotype of human monocytes.

  4. Similarities and differences between helminth parasites and cancer cell lines in shaping human monocytes: Insights into parallel mechanisms of immune evasion.

    Science.gov (United States)

    Narasimhan, Prakash Babu; Akabas, Leor; Tariq, Sameha; Huda, Naureen; Bennuru, Sasisekhar; Sabzevari, Helen; Hofmeister, Robert; Nutman, Thomas B; Tolouei Semnani, Roshanak

    2018-04-01

    A number of features at the host-parasite interface are reminiscent of those that are also observed at the host-tumor interface. Both cancer cells and parasites establish a tissue microenvironment that allows for immune evasion and may reflect functional alterations of various innate cells. Here, we investigated how the phenotype and function of human monocytes is altered by exposure to cancer cell lines and if these functional and phenotypic alterations parallel those induced by exposure to helminth parasites. Thus, human monocytes were exposed to three different cancer cell lines (breast, ovarian, or glioblastoma) or to live microfilariae (mf) of Brugia malayi-a causative agent of lymphatic filariasis. After 2 days of co-culture, monocytes exposed to cancer cell lines showed markedly upregulated expression of M1-associated (TNF-α, IL-1β), M2-associated (CCL13, CD206), Mreg-associated (IL-10, TGF-β), and angiogenesis associated (MMP9, VEGF) genes. Similar to cancer cell lines, but less dramatically, mf altered the mRNA expression of IL-1β, CCL13, TGM2 and MMP9. When surface expression of the inhibitory ligands PDL1 and PDL2 was assessed, monocytes exposed to both cancer cell lines and to live mf significantly upregulated PDL1 and PDL2 expression. In contrast to exposure to mf, exposure to cancer cell lines increased the phagocytic ability of monocytes and reduced their ability to induce T cell proliferation and to expand Granzyme A+ CD8+ T cells. Our data suggest that despite the fact that helminth parasites and cancer cell lines are extraordinarily disparate, they share the ability to alter the phenotype of human monocytes.

  5. Three-dimensional structure of a Streptomyces sviceus GNAT acetyltransferase with similarity to the C-terminal domain of the human GH84 O-GlcNAcase

    International Nuclear Information System (INIS)

    He, Yuan; Roth, Christian; Turkenburg, Johan P.; Davies, Gideon J.

    2013-01-01

    The crystal structure of a bacterial acetyltransferase with 27% sequence identity to the C-terminal domain of human O-GlcNAcase has been solved at 1.5 Å resolution. This S. sviceus protein is compared with known GCN5-related acetyltransferases, adding to the diversity observed in this superfamily. The mammalian O-GlcNAc hydrolysing enzyme O-GlcNAcase (OGA) is a multi-domain protein with glycoside hydrolase activity in the N-terminus and with a C-terminal domain that has low sequence similarity to known acetyltransferases, prompting speculation, albeit controversial, that the C-terminal domain may function as a histone acetyltransferase (HAT). There are currently scarce data available regarding the structure and function of this C-terminal region. Here, a bacterial homologue of the human OGA C-terminal domain, an acetyltransferase protein (accession No. ZP-05014886) from Streptomyces sviceus (SsAT), was cloned and its crystal structure was solved to high resolution. The structure reveals a conserved protein core that has considerable structural homology to the acetyl-CoA (AcCoA) binding site of GCN5-related acetyltransferases (GNATs). Calorimetric data further confirm that SsAT is indeed able to bind AcCoA in solution with micromolar affinity. Detailed structural analysis provided insight into the binding of AcCoA. An acceptor-binding cavity was identified, indicating that the physiological substrate of SsAT may be a small molecule. Consistent with recently published work, the SsAT structure further questions a HAT function for the human OGA domain

  6. Three-dimensional structure of a Streptomyces sviceus GNAT acetyltransferase with similarity to the C-terminal domain of the human GH84 O-GlcNAcase

    Energy Technology Data Exchange (ETDEWEB)

    He, Yuan [Northwest University, Xi’an 710069 (China); The University of York, York YO10 5DD (United Kingdom); Roth, Christian; Turkenburg, Johan P.; Davies, Gideon J., E-mail: gideon.davies@york.ac.uk [The University of York, York YO10 5DD (United Kingdom); Northwest University, Xi’an 710069 (China)

    2014-01-01

    The crystal structure of a bacterial acetyltransferase with 27% sequence identity to the C-terminal domain of human O-GlcNAcase has been solved at 1.5 Å resolution. This S. sviceus protein is compared with known GCN5-related acetyltransferases, adding to the diversity observed in this superfamily. The mammalian O-GlcNAc hydrolysing enzyme O-GlcNAcase (OGA) is a multi-domain protein with glycoside hydrolase activity in the N-terminus and with a C-terminal domain that has low sequence similarity to known acetyltransferases, prompting speculation, albeit controversial, that the C-terminal domain may function as a histone acetyltransferase (HAT). There are currently scarce data available regarding the structure and function of this C-terminal region. Here, a bacterial homologue of the human OGA C-terminal domain, an acetyltransferase protein (accession No. ZP-05014886) from Streptomyces sviceus (SsAT), was cloned and its crystal structure was solved to high resolution. The structure reveals a conserved protein core that has considerable structural homology to the acetyl-CoA (AcCoA) binding site of GCN5-related acetyltransferases (GNATs). Calorimetric data further confirm that SsAT is indeed able to bind AcCoA in solution with micromolar affinity. Detailed structural analysis provided insight into the binding of AcCoA. An acceptor-binding cavity was identified, indicating that the physiological substrate of SsAT may be a small molecule. Consistent with recently published work, the SsAT structure further questions a HAT function for the human OGA domain.

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

    Science.gov (United States)

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

    2012-09-01

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

  8. Fold-recognition and comparative modeling of human α2,3-sialyltransferases reveal their sequence and structural similarities to CstII from Campylobacter jejuni

    Directory of Open Access Journals (Sweden)

    Balaji Petety V

    2006-04-01

    Full Text Available Abstract Background The 3-D structure of none of the eukaryotic sialyltransferases (SiaTs has been determined so far. Sequence alignment algorithms such as BLAST and PSI-BLAST could not detect a homolog of these enzymes from the protein databank. SiaTs, thus, belong to the hard/medium target category in the CASP experiments. The objective of the current work is to model the 3-D structures of human SiaTs which transfer the sialic acid in α2,3-linkage viz., ST3Gal I, II, III, IV, V, and VI, using fold-recognition and comparative modeling methods. The pair-wise sequence similarity among these six enzymes ranges from 41 to 63%. Results Unlike the sequence similarity servers, fold-recognition servers identified CstII, a α2,3/8 dual-activity SiaT from Campylobacter jejuni as the homolog of all the six ST3Gals; the level of sequence similarity between CstII and ST3Gals is only 15–20% and the similarity is restricted to well-characterized motif regions of ST3Gals. Deriving template-target sequence alignments for the entire ST3Gal sequence was not straightforward: the fold-recognition servers could not find a template for the region preceding the L-motif and that between the L- and S-motifs. Multiple structural templates were identified to model these regions and template identification-modeling-evaluation had to be performed iteratively to choose the most appropriate templates. The modeled structures have acceptable stereochemical properties and are also able to provide qualitative rationalizations for some of the site-directed mutagenesis results reported in literature. Apart from the predicted models, an unexpected but valuable finding from this study is the sequential and structural relatedness of family GT42 and family GT29 SiaTs. Conclusion The modeled 3-D structures can be used for docking and other modeling studies and for the rational identification of residues to be mutated to impart desired properties such as altered stability, substrate

  9. Potency of full-length MGF to induce maximal activation of the IGF-I R Is similar to recombinant human IGF-I at high equimolar concentrations

    NARCIS (Netherlands)

    J.A.M.J.L. Janssen (Joseph); L.J. Hofland (Leo); C.J. Strasburger; E.S.R.D. Van Dungen (Elisabeth S.R. Den); M. Thevis (Mario)

    2016-01-01

    textabstractAims To compare full-length mechano growth factor (full-length MGF) with human recombinant insulin-like growth factor-I (IGF-I) and human recombinant insulin (HI) in their ability to activate the human IGF-I receptor (IGF-IR), the human insulin receptor (IR-A) and the human insulin

  10. Human immunodeficiency virus type 1 subtype B ancestral envelope protein is functional and elicits neutralizing antibodies in rabbits similar to those elicited by a circulating subtype B envelope.

    Science.gov (United States)

    Doria-Rose, N A; Learn, G H; Rodrigo, A G; Nickle, D C; Li, F; Mahalanabis, M; Hensel, M T; McLaughlin, S; Edmonson, P F; Montefiori, D; Barnett, S W; Haigwood, N L; Mullins, J I

    2005-09-01

    Human immunodeficiency virus type 1 (HIV-1) is a difficult target for vaccine development, in part because of its ever-expanding genetic diversity and attendant capacity to escape immunologic recognition. Vaccine efficacy might be improved by maximizing immunogen antigenic similarity to viruses likely to be encountered by vaccinees. To this end, we designed a prototype HIV-1 envelope vaccine using a deduced ancestral state for the env gene. The ancestral state reconstruction method was shown to be >95% accurate by computer simulation and 99.8% accurate when estimating the known inoculum used in an experimental infection study in rhesus macaques. Furthermore, the deduced ancestor gene differed from the set of sequences used to derive the ancestor by an average of 12.3%, while these latter sequences were an average of 17.3% different from each other. A full-length ancestral subtype B HIV-1 env gene was constructed and shown to produce a glycoprotein of 160 kDa that bound and fused with cells expressing the HIV-1 coreceptor CCR5. This Env was also functional in a virus pseudotype assay. When either gp160- or gp140-expressing plasmids and recombinant gp120 were used to immunize rabbits in a DNA prime-protein boost regimen, the artificial gene induced immunoglobulin G antibodies capable of weakly neutralizing heterologous primary HIV-1 strains. The results were similar for rabbits immunized in parallel with a natural isolate, HIV-1 SF162. Further design efforts to better present conserved neutralization determinants are warranted.

  11. The coupling of cerebral blood flow and oxygen metabolism with brain activation is similar for simple and complex stimuli in human primary visual cortex.

    Science.gov (United States)

    Griffeth, Valerie E M; Simon, Aaron B; Buxton, Richard B

    2015-01-01

    Quantitative functional MRI (fMRI) experiments to measure blood flow and oxygen metabolism coupling in the brain typically rely on simple repetitive stimuli. Here we compared such stimuli with a more naturalistic stimulus. Previous work on the primary visual cortex showed that direct attentional modulation evokes a blood flow (CBF) response with a relatively large oxygen metabolism (CMRO2) response in comparison to an unattended stimulus, which evokes a much smaller metabolic response relative to the flow response. We hypothesized that a similar effect would be associated with a more engaging stimulus, and tested this by measuring the primary human visual cortex response to two contrast levels of a radial flickering checkerboard in comparison to the response to free viewing of brief movie clips. We did not find a significant difference in the blood flow-metabolism coupling (n=%ΔCBF/%ΔCMRO2) between the movie stimulus and the flickering checkerboards employing two different analysis methods: a standard analysis using the Davis model and a new analysis using a heuristic model dependent only on measured quantities. This finding suggests that in the primary visual cortex a naturalistic stimulus (in comparison to a simple repetitive stimulus) is either not sufficient to provoke a change in flow-metabolism coupling by attentional modulation as hypothesized, that the experimental design disrupted the cognitive processes underlying the response to a more natural stimulus, or that the technique used is not sensitive enough to detect a small difference. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Kinetic and Thermodynamic Rationale for SAHA Being a Preferential Human HDAC8 Inhibitor as Compared to the Structurally Similar Ligand, TSA

    Science.gov (United States)

    Singh, Raushan K.; Lall, Naveena; Leedahl, Travis S.; McGillivray, Abigail; Mandal, Tanmay; Haldar, Manas; Mallik, Sanku; Cook, Gregory; Srivastava, D.K.

    2013-01-01

    Of the different hydroxamate-based histone deacetylase (HDAC) inhibitors, Suberoylanilide hydroxamic acid (SAHA) has been approved by the FDA for treatment of T-cell lymphoma. Interestingly, a structurally similar inhibitor, Trichostatin A (TSA), which has a higher in vitro inhibitory-potency against HDAC8, reportedly shows a poor efficacy in clinical settings. In order to gain the molecular insight into the above discriminatory feature, we performed transient kinetic and isothermal titration calorimetric studies for the interaction of SAHA and TSA to the recombinant form of human HDAC8. The transient kinetic data revealed that the binding of both the inhibitors to the enzyme showed the biphasic profiles, which represented an initial encounter of enzyme with the inhibitor followed by the isomerization of the transient enzyme-inhibitor complexes. The temperature-dependent transient kinetic studies with the above inhibitors revealed that the bimolecular process is primarily dominated by favorable enthalpic changes, as opposed to the isomerization step; which is solely contributed by entropic changes. The standard binding-enthalpy (ΔH0) of SAHA, deduced from the transient kinetic as well as the isothermal titration calorimetric experiments, was 2–3 kcal/mol higher as compared to TSA. The experimental data presented herein suggests that SAHA serves as a preferential (target-specific/selective) HDAC8 inhibitor as compared to TSA. Arguments are presented that the detailed kinetic and thermodynamic studies may guide in the rational design of HDAC inhibitors as therapeutic agents. PMID:24079912

  13. Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology

    Directory of Open Access Journals (Sweden)

    Daniele Bertoglio

    2017-11-01

    Full Text Available The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE. As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE. Wistar Han (Charles River, France and Sprague-Dawley (Harlan, The Netherlands rats were subjected to KASE using the Hellier kainic acid (KA and a modified injection scheme. Duration of SE and latent phase were characterized by video-electroencephalography (vEEG in a subgroup of animals, while animals were sacrificed 1 week (subacute phase and 12 weeks (chronic phase post-SE. In the 12 weeks post-SE groups, seizures were monitored with vEEG. Neuronal loss (neuronal nuclei, microglial activation (OX-42 and translocator protein, and neurodegeneration (Fluorojade C were assessed. First, the Hellier protocol caused very high mortality in WH/CR rats compared to SD/H animals. The modified protocol resulted in a similar SE severity for WH/CR and SD/H rats, but effectively improved survival rates. The latent phase was significantly shorter (p < 0.0001 in SD/H (median 8.3 days animals compared to WH/CR (median 15.4 days. During the chronic phase, SD/H rats had more seizures/day compared to WH/CR animals (p < 0.01. However, neuronal degeneration and cell loss were overall more extensive in WH/CR than in SD/H rats; microglia activation was similar between the two strains 1 week post-SE, but higher in WH/CR rats 12 weeks post-SE. These neuropathological differences may be more related to the distinct neurotoxic effects of KA in the two rat strains than being the outcome of seizure

  14. Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology

    Science.gov (United States)

    Bertoglio, Daniele; Amhaoul, Halima; Van Eetveldt, Annemie; Houbrechts, Ruben; Van De Vijver, Sebastiaan; Ali, Idrish; Dedeurwaerdere, Stefanie

    2017-01-01

    The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE) rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE). As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE). Wistar Han (Charles River, France) and Sprague-Dawley (Harlan, The Netherlands) rats were subjected to KASE using the Hellier kainic acid (KA) and a modified injection scheme. Duration of SE and latent phase were characterized by video-electroencephalography (vEEG) in a subgroup of animals, while animals were sacrificed 1 week (subacute phase) and 12 weeks (chronic phase) post-SE. In the 12 weeks post-SE groups, seizures were monitored with vEEG. Neuronal loss (neuronal nuclei), microglial activation (OX-42 and translocator protein), and neurodegeneration (Fluorojade C) were assessed. First, the Hellier protocol caused very high mortality in WH/CR rats compared to SD/H animals. The modified protocol resulted in a similar SE severity for WH/CR and SD/H rats, but effectively improved survival rates. The latent phase was significantly shorter (p < 0.0001) in SD/H (median 8.3 days) animals compared to WH/CR (median 15.4 days). During the chronic phase, SD/H rats had more seizures/day compared to WH/CR animals (p < 0.01). However, neuronal degeneration and cell loss were overall more extensive in WH/CR than in SD/H rats; microglia activation was similar between the two strains 1 week post-SE, but higher in WH/CR rats 12 weeks post-SE. These neuropathological differences may be more related to the distinct neurotoxic effects of KA in the two rat strains than being the outcome of seizure burden

  15. Neuropathologic features in the hippocampus and cerebellum of three older men with fragile X syndrome

    Directory of Open Access Journals (Sweden)

    Greco Claudia M

    2011-02-01

    Full Text Available Abstract Background Fragile X syndrome (FXS is the most common inherited form of intellectual disability, and is the most common single-gene disorder known to be associated with autism. Despite recent advances in functional neuroimaging and our understanding of the molecular pathogenesis, only limited neuropathologic information on FXS is available. Methods Neuropathologic examinations were performed on post-mortem brain tissue from three older men (aged 57, 64 and 78 years who had received a clinical or genetic diagnosis of FXS. In each case, physical and cognitive features were typical of FXS, and one man was also diagnosed with autism. Guided by reports of clinical and neuroimaging abnormalities of the limbic system and cerebellum of individuals with FXS, the current analysis focused on neuropathologic features present in the hippocampus and the cerebellar vermis. Results Histologic and immunologic staining revealed abnormalities in both the hippocampus and cerebellar vermis. Focal thickening of hippocampal CA1 and irregularities in the appearance of the dentate gyrus were identified. All lobules of the cerebellar vermis and the lateral cortex of the posterior lobe of the cerebellum had decreased numbers of Purkinje cells, which were occasionally misplaced, and often lacked proper orientation. There were mild, albeit excessive, undulations of the internal granular cell layer, with patchy foliar white matter axonal and astrocytic abnormalities. Quantitative analysis documented panfoliar atrophy of both the anterior and posterior lobes of the vermis, with preferential atrophy of the posterior lobule (VI to VII compared with age-matched normal controls. Conclusions Significant morphologic changes in the hippocampus and cerebellum in three adult men with FXS were identified. This pattern of pathologic features supports the idea that primary defects in neuronal migration, neurogenesis and aging may underlie the neuropathology reported in FXS.

  16. HANSENS DISEASE : STUDY OF CLINICAL, NEUROPATHOLOGICAL, NEUROPHYSIOLOGICAL PATTERN OF LEPROUS NEUROPATHY

    OpenAIRE

    Vijay Kumar; Ajay Kumar

    2015-01-01

    A need still exists to determine the clinical and neurophysiological characteristics of leprosy neuropathy at distinct times of the disease by different methods that measure the various nerve fiber functions. A prospective clinical study was performed 100 patients of clinically proven Hansen’s will take in study and given diagnosis is made by dermatologist and neurologist. For Study of Clinical, Neuropathological , Neurophysiological Pattern of leprous neuropathy and r...

  17. Next-Generation Sequencing in Neuropathologic Diagnosis of Infections of the Nervous System (Open Access)

    Science.gov (United States)

    2016-06-13

    nervous system ABSTRACT Objective: To determine the feasibility of next-generation sequencing (NGS) microbiome ap- proaches in the diagnosis of infectious...V, van Doorn HR, Nghia HD, et al. Identification of a new cyclovirus in cerebrospinal fluid of patients with acute central nervous system infections...Kumar, et al. system Next-generation sequencing in neuropathologic diagnosis of infections of the nervous This information is current as of June 13

  18. Neuropathologic features in the hippocampus and cerebellum of three older men with fragile X syndrome

    Science.gov (United States)

    2011-01-01

    Background Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, and is the most common single-gene disorder known to be associated with autism. Despite recent advances in functional neuroimaging and our understanding of the molecular pathogenesis, only limited neuropathologic information on FXS is available. Methods Neuropathologic examinations were performed on post-mortem brain tissue from three older men (aged 57, 64 and 78 years) who had received a clinical or genetic diagnosis of FXS. In each case, physical and cognitive features were typical of FXS, and one man was also diagnosed with autism. Guided by reports of clinical and neuroimaging abnormalities of the limbic system and cerebellum of individuals with FXS, the current analysis focused on neuropathologic features present in the hippocampus and the cerebellar vermis. Results Histologic and immunologic staining revealed abnormalities in both the hippocampus and cerebellar vermis. Focal thickening of hippocampal CA1 and irregularities in the appearance of the dentate gyrus were identified. All lobules of the cerebellar vermis and the lateral cortex of the posterior lobe of the cerebellum had decreased numbers of Purkinje cells, which were occasionally misplaced, and often lacked proper orientation. There were mild, albeit excessive, undulations of the internal granular cell layer, with patchy foliar white matter axonal and astrocytic abnormalities. Quantitative analysis documented panfoliar atrophy of both the anterior and posterior lobes of the vermis, with preferential atrophy of the posterior lobule (VI to VII) compared with age-matched normal controls. Conclusions Significant morphologic changes in the hippocampus and cerebellum in three adult men with FXS were identified. This pattern of pathologic features supports the idea that primary defects in neuronal migration, neurogenesis and aging may underlie the neuropathology reported in FXS. PMID:21303513

  19. Neuropathological biomarker candidates in brain tumors: key issues for translational efficiency.

    Science.gov (United States)

    Hainfellner, J A; Heinzl, H

    2010-01-01

    Brain tumors comprise a large spectrum of rare malignancies in children and adults that are often associated with severe neurological symptoms and fatal outcome. Neuropathological tumor typing provides both prognostic and predictive tissue information which is the basis for optimal postoperative patient management and therapy. Molecular biomarkers may extend and refine prognostic and predictive information in a brain tumor case, providing more individualized and optimized treatment options. In the recent past a few neuropathological brain tumor biomarkers have translated smoothly into clinical use whereas many candidates show protracted translation. We investigated the causes of protracted translation of candidate brain tumor biomarkers. Considering the research environment from personal, social and systemic perspectives we identified eight determinants of translational success: methodology, funding, statistics, organization, phases of research, cooperation, self-reflection, and scientific progeny. Smoothly translating biomarkers are associated with low degrees of translational complexity whereas biomarkers with protracted translation are associated with high degrees. Key issues for translational efficiency of neuropathological brain tumor biomarker research seem to be related to (i) the strict orientation to the mission of medical research, that is the improval of medical practice as primordial purpose of research, (ii) definition of research priorities according to clinical needs, and (iii) absorption of translational complexities by means of operatively beneficial standards. To this end, concrete actions should comprise adequate scientific education of young investigators, and shaping of integrative diagnostics and therapy research both on the local level and the level of influential international brain tumor research platforms.

  20. Core neuropathological abnormalities in progranulin-deficient mice are penetrant on multiple genetic backgrounds.

    Science.gov (United States)

    Petkau, T L; Hill, A; Leavitt, B R

    2016-02-19

    Loss-of-function mutations in the progranulin gene (GRN) are a common cause of familial frontotemporal lobar degeneration (FTLD). A high degree of heterogeneity in the age-of-onset, duration of disease, and clinical presentation of FTLD, even among families carrying the same GRN mutation, suggests that additional modifying genes may be important to pathogenesis. Progranulin-knockout mice display subtle behavioral abnormalities and progressive neuropathological changes, as well as altered dendritic morphology and synaptic deficits in the hippocampus. In this study we evaluated multiple neuropathological endpoints in aged progranulin knockout mice and their wild-type littermates on two different genetic backgrounds: C57Bl/6 and 129/SvImJ. We find that in most brain regions, both strains are susceptible to progranulin-mediated neuropathological phenotypes, including astrogliosis, microgliosis, and highly accelerated deposition of the aging pigment lipofuscin. Neuroinflammation due to progranulin deficiency is exaggerated in the B6 strain and present, but less pronounced, in the 129 strain. Differences between the strains in hippocampal neuron counts and neuronal morphology suggest a complex role for progranulin in the hippocampus. We conclude that core progranulin-mediated neurodegenerative phenotypes are penetrant on multiple inbred mouse strains, but that genetic background modulates progranulin's role in neuroinflammation and hippocampal biology. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Early life linguistic ability, late life cognitive function, and neuropathology: findings from the Nun Study.

    Science.gov (United States)

    Riley, Kathryn P; Snowdon, David A; Desrosiers, Mark F; Markesbery, William R

    2005-03-01

    The relationships between early life variables, cognitive function, and neuropathology were examined in participants in the Nun Study who were between the ages of 75 and 95. Our early life variable was idea density, which is a measure of linguistic ability, derived from autobiographies written at a mean age of 22 years. Six discrete categories of cognitive function, including mild cognitive impairments, were evaluated, using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of cognitive tests. Neuropathologic data included Braak staging, neurofibrillary tangle and senile plaque counts, brain weight, degree of cerebral atrophy, severity of atherosclerosis, and the presence of brain infarcts. Early-life idea density was significantly related to the categories of late-life cognitive function, including mild cognitive impairments: low idea density was associated with greater impairment. Low idea density also was significantly associated with lower brain weight, higher degree of cerebral atrophy, more severe neurofibrillary pathology, and the likelihood of meeting neuropathologic criteria for Alzheimer's disease.

  2. A Clinical, Neuropathological and Genetic Study of Homozygous A467T POLG-Related Mitochondrial Disease.

    Directory of Open Access Journals (Sweden)

    Sanjeev Rajakulendran

    Full Text Available Mutations in the nuclear gene POLG (encoding the catalytic subunit of DNA polymerase gamma are an important cause of mitochondrial disease. The most common POLG mutation, A467T, appears to exhibit considerable phenotypic heterogeneity. The mechanism by which this single genetic defect results in such clinical diversity remains unclear. In this study we evaluate the clinical, neuropathological and mitochondrial genetic features of four unrelated patients with homozygous A467T mutations. One patient presented with the severe and lethal Alpers-Huttenlocher syndrome, which was confirmed on neuropathology, and was found to have a depletion of mitochondrial DNA (mtDNA. Of the remaining three patients, one presented with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS, one with a phenotype in the Myoclonic Epilepsy, Myopathy and Sensory Ataxia (MEMSA spectrum and one with Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoplegia (SANDO. All three had secondary accumulation of multiple mtDNA deletions. Complete sequence analysis of muscle mtDNA using the MitoChip resequencing chip in all four cases demonstrated significant variation in mtDNA, including a pathogenic MT-ND5 mutation in one patient. These data highlight the variable and overlapping clinical and neuropathological phenotypes and downstream molecular defects caused by the A467T mutation, which may result from factors such as the mtDNA genetic background, nuclear genetic modifiers and environmental stressors.

  3. A retrospective study of the neuropathology and diagnosis of naturally occurring feline infectious peritonitis.

    Science.gov (United States)

    Rissi, Daniel R

    2018-05-01

    Feline infectious peritonitis (FIP) is one of the most important viral diseases of cats worldwide. Our study describes the neuropathology and the diagnostic features of 26 cases of FIP in domestic cats. The average age of affected individuals was 11.8 mo, and there was no sex or breed predisposition. Clinical neurologic signs were noted in 22 cases, and rabies was clinically suspected in 11 cases. Twenty cats had lesions in multiple organs, and 6 cats had lesions only in the brain. Gross neuropathologic changes occurred in 15 cases and consisted of hydrocephalus (10 cases), cerebellar herniation through the foramen magnum (6 cases), cerebral swelling with flattening of gyri (2 cases), and accumulation of fibrin within ventricles (2 cases) or leptomeninges (1 case). Histologically, 3 main distinct distributions of neuropathologic changes were observed, namely periventricular encephalitis (12 cases), rhombencephalitis (8 cases), and diffuse leptomeningitis with superficial encephalitis (6 cases). Fresh tissue samples were submitted for fluorescent antibody testing (FAT) after autopsy in 17 cases, and positive results were found in only 7 cases. Immunohistochemistry (IHC) for feline coronavirus confirmed the diagnosis in all 26 cases. IHC appears to be a more sensitive and reliable test for confirmation of FIP than is FAT.

  4. Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings

    Science.gov (United States)

    Michalak, Zuzanna; Wright, Gabriella; Dawson, Timothy; Hilton, David; Joshi, Abhijit; Diehl, Beate; Koepp, Matthias; Lhatoo, Samden; Sander, Josemir W.; Sisodiya, Sanjay M.

    2015-01-01

    Aims Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy. For classification of definite SUDEP, a post mortem (PM), including anatomical and toxicological examination, is mandatory to exclude other causes of death. We audited PM practice as well as the value of brain examination in SUDEP. Methods We reviewed 145 PM reports in SUDEP cases from four UK neuropathology centres. Data were extracted for clinical epilepsy details, circumstances of death and neuropathological findings. Results Macroscopic brain abnormalities were identified in 52% of cases. Mild brain swelling was present in 28%, and microscopic pathologies relevant to cause or effect of seizures were seen in 89%. Examination based on whole fixed brains (76.6% of all PMs), and systematic regional sampling was associated with higher detection rates of underlying pathology (P epilepsy history and investigations. Conclusion Our findings support the contribution of examination of the whole fixed brain in SUDEP, with high rates of detection of relevant pathology. Availability of full clinical epilepsy‐related information at the time of PM could potentially further improve detection through targeted tissue sampling. Apart from confirmation of SUDEP, complete neuropathological examination contributes to evaluation of risk factors as well as helping to direct future research into underlying causes. PMID:26300477

  5. Incidence of mammary tumors in the canine population living in the Veneto region (Northeastern Italy): Risk factors and similarities to human breast cancer.

    Science.gov (United States)

    Vascellari, Marta; Capello, Katia; Carminato, Antonio; Zanardello, Claudia; Baioni, Elisa; Mutinelli, Franco

    2016-04-01

    Although mammary gland tumors (MT) are the most-common type of tumor in intact female dogs, there is little information about their incidence in dog population. Data on MT in female dogs was retrieved from the Animal Tumor registry of dogs and cats of Venice and Vicenza provinces during 2005-2013 and was analyzed to visualize crude incidence rates by breed and across age categories. Overall, 2744 mammary tumors were reported accounting for 54% of all tumors in female dogs. The annual incidence rate (IR) was 250 cases per 100,000 dogs. The most frequent malignant tumors were complex carcinomas, consisting of both epithelial and myoepithelial tissues (IR=71.89), and simple carcinomas (IR=62.59). The MT incidence rate increased through the study period; particularly in the last 4 years, and malignant neoplasms occurred more frequently (70%) than the benign counterparts (30%). Seventy-four percent of tumors were diagnosed in intact females, and the mean age at diagnosis was significantly higher for spayed dogs than for intact ones. MT were less frequent in dogs younger than 6 years and increased up to approximately 60% for ages between 8 and 13 years. The purebred dogs had a higher probability to have a malignant neoplasm than mixed-breed dogs, particularly in dogs younger than 7 years, and the Samoyed, Dobermann, Schnauzer and Yorkshire Terrier breeds were more inclined to develop malignant MT. The incidence of MT in dogs is increasing, and IRs are comparable to that in women. The epidemiological similarities between dogs and women support the validity of canine MT as a model for human breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Structure-function similarities between a plant receptor-like kinase and the human interleukin-1 receptor-associated kinase-4.

    Science.gov (United States)

    Klaus-Heisen, Dörte; Nurisso, Alessandra; Pietraszewska-Bogiel, Anna; Mbengue, Malick; Camut, Sylvie; Timmers, Ton; Pichereaux, Carole; Rossignol, Michel; Gadella, Theodorus W J; Imberty, Anne; Lefebvre, Benoit; Cullimore, Julie V

    2011-04-01

    Phylogenetic analysis has previously shown that plant receptor-like kinases (RLKs) are monophyletic with respect to the kinase domain and share an evolutionary origin with the animal interleukin-1 receptor-associated kinase/Pelle-soluble kinases. The lysin motif domain-containing receptor-like kinase-3 (LYK3) of the legume Medicago truncatula shows 33% amino acid sequence identity with human IRAK-4 over the kinase domain. Using the structure of this animal kinase as a template, homology modeling revealed that the plant RLK contains structural features particular to this group of kinases, including the tyrosine gatekeeper and the N-terminal extension α-helix B. Functional analysis revealed the importance of these conserved features for kinase activity and suggests that kinase activity is essential for the biological role of LYK3 in the establishment of the root nodule nitrogen-fixing symbiosis with rhizobia bacteria. The kinase domain of LYK3 has dual serine/threonine and tyrosine specificity, and mass spectrometry analysis identified seven serine, eight threonine, and one tyrosine residue as autophosphorylation sites in vitro. Three activation loop serine/threonine residues are required for biological activity, and molecular dynamics simulations suggest that Thr-475 is the prototypical phosphorylated residue that interacts with the conserved arginine in the catalytic loop, whereas Ser-471 and Thr-472 may be secondary sites. A threonine in the juxtamembrane region and two threonines in the C-terminal lobe of the kinase domain are important for biological but not kinase activity. We present evidence that the structure-function similarities that we have identified between LYK3 and IRAK-4 may be more widely applicable to plant RLKs in general.

  7. Cerebellar oxidative DNA damage and altered DNA methylation in the BTBR T+tf/J mouse model of autism and similarities with human post mortem cerebellum.

    Directory of Open Access Journals (Sweden)

    Svitlana Shpyleva

    Full Text Available The molecular pathogenesis of autism is complex and involves numerous genomic, epigenomic, proteomic, metabolic, and physiological alterations. Elucidating and understanding the molecular processes underlying the pathogenesis of autism is critical for effective clinical management and prevention of this disorder. The goal of this study is to investigate key molecular alterations postulated to play a role in autism and their role in the pathophysiology of autism. In this study we demonstrate that DNA isolated from the cerebellum of BTBR T+tf/J mice, a relevant mouse model of autism, and from human post-mortem cerebellum of individuals with autism, are both characterized by an increased levels of 8-oxo-7-hydrodeoxyguanosine (8-oxodG, 5-methylcytosine (5mC, and 5-hydroxymethylcytosine (5hmC. The increase in 8-oxodG and 5mC content was associated with a markedly reduced expression of the 8-oxoguanine DNA-glycosylase 1 (Ogg1 and increased expression of de novo DNA methyltransferases 3a and 3b (Dnmt3a and Dnmt3b. Interestingly, a rise in the level of 5hmC occurred without changes in the expression of ten-eleven translocation expression 1 (Tet1 and Tet2 genes, but significantly correlated with the presence of 8-oxodG in DNA. This finding and similar elevation in 8-oxodG in cerebellum of individuals with autism and in the BTBR T+tf/J mouse model warrant future large-scale studies to specifically address the role of OGG1 alterations in pathogenesis of autism.

  8. Human rotavirus strains bearing VP4 gene P[6] allele recovered from asymptomatic or symptomatic infections share similar, if not identical, VP4 neutralization specificities

    International Nuclear Information System (INIS)

    Hoshino, Yasutaka; Jones, Ronald W.; Ross, Jerri; Santos, Norma; Kapikian, Albert Z.

    2003-01-01

    A rotavirus VP4 gene P[6] allele has been documented in a number of countries to be characteristically associated with an endemic predominantly asymptomatic infection in neonates in maternity hospital nurseries. The mechanisms underlying the endemicity and asymptomatic nature of such neonatal infections remain unknown. Rotavirus strains sharing this same P genotype, however, have more recently been recovered from an increasing number of symptomatic diarrheal episodes in infants and young children in various parts of the world. Previously, we have shown that an asymptomatic P[6] rotavirus neonatal infection is not associated with a unique VP7 (G) serotype but may occur in conjunction with various G types. Although amino acid sequence comparisons of the VP4 gene between selected 'asymptomatic' and 'symptomatic' P[6] rotavirus strains have been reported and yielded information concerning their VP4 genotypes, serotypic comparisons of the outer capsid spike protein VP4 of such viruses have not been studied systematically by two-way cross-neutralizations. We determined the VP4 neutralization specificities of four asymptomatic and four symptomatic P[6] strains: two each of asymptomatic and symptomatic strains by two-way tests, and two each of additional asymptomatic and symptomatic strains by one-way tests. Both asymptomatic and symptomatic P[6] strains were shown to bear similar, if not identical, VP4 neutralization specificities. Thus, P[6] rotavirus strains causing asymptomatic or symptomatic infections did not appear to belong to unique P (VP4) serotypes. In addition, a close VP4 serotypic relationship between human P[6] rotavirus strains and the porcine P[6] rotavirus Gottfried strain was confirmed

  9. Academic productivity after retirement in pediatric neurology and neuropathology.

    Science.gov (United States)

    Sarnat, Harvey B

    2018-05-25

    Many academic neurologists and neuropathologists who retire at the peak of their careers continue to be productive in research and teaching, enhanced by years of experience and mature perspective. The early 20th-century model of institutions depending upon the generosity of such individuals to donate their time and efforts without proper recognition or compensation, despite the service, prestige, and recognition they bring to their institutions, should be reconsidered in the early 21st century in the context of fairness, honesty, dignity, and increased longevity. University pensions do not distinguish retirees who continue to contribute from those who stop working. This essay represents the author's personal reflections and experience, reinforced by similar thoughts and encouragement by numerous distinguished colleagues named at the end of the text. Funding of stipends for active emeritus professors lacks precedent but should be sought. © 2018 American Academy of Neurology.

  10. Survival in the pre-senile dementia frontotemporal lobar degeneration with TDP-43 proteinopathy: effects of genetic, demographic and neuropathological variables

    Directory of Open Access Journals (Sweden)

    Richard A. Armstrong

    2016-06-01

    Full Text Available Factors associated with survival were studied in 84 neuropathologically documented cases of the pre-senile dementia frontotemporal dementia lobar degeneration (FTLD with transactive response (TAR DNA-binding protein of 43 kDa (TDP-43 proteinopathy (FTLD-TDP. Kaplan-Meier survival analysis estimated mean survival as 7.9 years (range: 1-19 years, SD = 4.64. Familial and sporadic cases exhibited similar survival, including progranulin (GRN gene mutation cases. No significant differences in survival were associated with sex, disease onset, Braak disease stage, or disease subtype, but higher survival was associated with lower post-mortem brain weight. Survival was significantly reduced in cases with associated motor neuron disease (FTLD-MND but increased with Alzheimer’s disease (AD or hippocampal sclerosis (HS co-morbidity. Cox regression analysis suggested that reduced survival was associated with increased densities of neuronal cytoplasmic inclusions (NCI while increased survival was associated with greater densities of enlarged neurons (EN in the frontal and temporal lobes. The data suggest that: (1 survival in FTLD-TDP is more prolonged than typical in pre-senile dementia but shorter than some clinical subtypes such as the semantic variant of primary progressive aphasia (svPPA, (2 MND co-morbidity predicts poor survival, and (3 NCI may develop early and EN later in the disease. The data have implications for both neuropathological characterization and subtyping of FTLD-TDP.

  11. Preoperative Quantitative MR Tractography Compared with Visual Tract Evaluation in Patients with Neuropathologically Confirmed Gliomas Grades II and III: A Prospective Cohort Study

    International Nuclear Information System (INIS)

    Delgado, Anna F.; Nilsson, Markus; Latini, Francesco; Mårtensson, Johanna; Zetterling, Maria; Berntsson, Shala G.; Alafuzoff, Irina; Lätt, Jimmy; Larsson, Elna-Marie

    2016-01-01

    Background and Purpose. Low-grade gliomas show infiltrative growth in white matter tracts. Diffusion tensor tractography can noninvasively assess white matter tracts. The aim was to preoperatively assess tumor growth in white matter tracts using quantitative MR tractography (3T). The hypothesis was that suspected infiltrated tracts would have altered diffusional properties in infiltrated tract segments compared to noninfiltrated tracts. Materials and Methods. Forty-eight patients with suspected low-grade glioma were included after written informed consent and underwent preoperative diffusion tensor imaging in this prospective review-board approved study. Major white matter tracts in both hemispheres were tracked, segmented, and visually assessed for tumor involvement in thirty-four patients with gliomas grade II or III (astrocytomas or oligodendrogliomas) on postoperative neuropathological evaluation. Relative fractional anisotropy (rFA) and mean diffusivity (rMD) in tract segments were calculated and compared with visual evaluation and neuropathological diagnosis. Results. Tract segment infiltration on visual evaluation was associated with a lower rFA and high rMD in a majority of evaluated tract segments (89% and 78%, resp.). Grade II and grade III gliomas had similar infiltrating behavior. Conclusion. Quantitative MR tractography corresponds to visual evaluation of suspected tract infiltration. It may be useful for an objective preoperative evaluation of tract segment involvement

  12. Molecular Neuropathology of Astrocytes and Oligodendrocytes in Alcohol Use Disorders

    Directory of Open Access Journals (Sweden)

    José J. Miguel-Hidalgo

    2018-03-01

    Full Text Available Postmortem studies reveal structural and molecular alterations of astrocytes and oligodendrocytes in both the gray and white matter (GM and WM of the prefrontal cortex (PFC in human subjects with chronic alcohol abuse or dependence. These glial cellular changes appear to parallel and may largely explain structural and functional alterations detected using neuroimaging techniques in subjects with alcohol use disorders (AUDs. Moreover, due to the crucial roles of astrocytes and oligodendrocytes in neurotransmission and signal conduction, these cells are very likely major players in the molecular mechanisms underpinning alcoholism-related connectivity disturbances between the PFC and relevant interconnecting brain regions. The glia-mediated etiology of alcohol-related brain damage is likely multifactorial since metabolic, hormonal, hepatic and hemodynamic factors as well as direct actions of ethanol or its metabolites have the potential to disrupt distinct aspects of glial neurobiology. Studies in animal models of alcoholism and postmortem human brains have identified astrocyte markers altered in response to significant exposures to ethanol or during alcohol withdrawal, such as gap-junction proteins, glutamate transporters or enzymes related to glutamate and gamma-aminobutyric acid (GABA metabolism. Changes in these proteins and their regulatory pathways would not only cause GM neuronal dysfunction, but also disturbances in the ability of WM axons to convey impulses. In addition, alcoholism alters the expression of astrocyte and myelin proteins and of oligodendrocyte transcription factors important for the maintenance and plasticity of myelin sheaths in WM and GM. These changes are concomitant with epigenetic DNA and histone modifications as well as alterations in regulatory microRNAs (miRNAs that likely cause profound disturbances of gene expression and protein translation. Knowledge is also available about interactions between astrocytes and

  13. Spinal tract pathology in AIDS: postmortem MRI correlation with neuropathology

    Energy Technology Data Exchange (ETDEWEB)

    Santosh, C.G. [City Hospital, Edinburgh (United Kingdom). MRI Unit; Bell, J.E. [Western General Hospital, Edinburgh (United Kingdom). Neuropathology Lab.; Best, J.J.K. [City Hospital, Edinburgh (United Kingdom). MRI Unit

    1995-02-01

    Vacuolar myelopathy (VM) and tract pallor are poorly understood spinal tract abnormalities in patients with the acquired immunodeficiency syndrome (AIDS). We studied the ability of magnetic resonance imaging (MRI) to detect these changes in spinal cord specimens postmortem and whether criteria could be formulated which would allow these conditions to be differentiated from other lesions of the spinal cord in AIDS, such as lymphoma, cytomegalovirus (CMV) and human immunodeficiency virus (HIV) myelitis. We imaged 38 postmortem specimens of spinal cord. The MRI studies were interpreted blind. The specimens included cases of VM myelin pallor. CMV myeloradiculitis, HIV myelitis, lymphoma as well as normal cords, both HIV+ve and HIV-ve. MRI showed abnormal signal, suggestive of tract pathology, in 10 of the 14 cases with histopathological evidence of tract changes. The findings in VM and tract pallor on proton-density and T{sub 2}-weighted MRI were increased signal from the affected white-matter tracts, present on multiple contiguous slices and symmetrical in most cases. The pattern was sufficiently distinct to differentiate spinal tract pathology from other spinal cord lesions in AIDS. (orig.)

  14. Association between polychlorinated biphenyls and Parkinson's disease neuropathology.

    Science.gov (United States)

    Hatcher-Martin, Jaime M; Gearing, Marla; Steenland, Kyle; Levey, Allan I; Miller, Gary W; Pennell, Kurt D

    2012-10-01

    Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson's disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson's disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson's disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson's disease patients. When stratified by sex, the female Parkinson's disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson's disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson's disease-related pathology. Furthermore, these data support epidemiological and laboratory studies

  15. Association between polychlorinated biphenyls and Parkinson’s disease neuropathology

    Science.gov (United States)

    Hatcher-Martin, Jaime M.; Gearing, Marla; Steenland, Kyle; Levey, Allan I.; Miller, Gary W.; Pennell, Kurt D.

    2012-01-01

    Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson’s disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson’s disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson’s disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson’s disease patients. When stratified by sex, the female Parkinson’s disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson’s disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson’s disease-related pathology. Furthermore, these data support epidemiological and

  16. Selenomethionine Ameliorates Neuropathology in the Olfactory Bulb of a Triple Transgenic Mouse Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Zhong-Hao Zhang

    2016-09-01

    Full Text Available Olfactory dysfunction is an early and common symptom in Alzheimer′s disease (AD and is reported to be related to several pathologic changes, including the deposition of Aβ and hyperphosphorylated tau protein as well as synaptic impairment. Selenomethionine (Se-Met, the major form of selenium in animals and humans, may be a promising therapeutic option for AD as it decreases the deposition of Aβ and tau hyperphosphorylation in a triple transgenic mouse model of AD (3× Tg-AD. In this study, 4-month-old AD mice were treated with 6 µg/mL Se-Met in drinking water for 12 weeks and the effect of Se-Met on neuropathological deficits in olfactory bulb (OB of 3× Tg-AD mice was investigated. The administration of Se-Met effectively decreased the production and deposition of Aβ by inhibiting β-site amyloid precursor protein cleaving enzyme 1 (BACE1-regulated amyloid precursor protein (APP processing and reduced the level of total tau and phosphorylated tau, which depended on depressing the activity and expression of glycogen synthase kinase-3β (GSK-3β and cyclin-dependent kinase 5 (CDK5. Meanwhile, Se-Met reduced glial activation, relieved neuroinflammation and attenuated neuronal cell death in the OB of AD mice. So Se-Met could improve pathologic changes of AD in the OB, which further demonstrated the potential therapeutic effect of Se-Met in AD.

  17. Distinguishing the impacts of human activities and climate variability on runoff and sediment load change based on paired periods with similar weather conditions

    NARCIS (Netherlands)

    Wang, Fei; Hessel, Rudi; Mu, Xingmin; Maroulis, Jerry; Zhao, Guangju; Geissen, Violette; Ritsema, Coen

    2015-01-01

    Runoff and sediment loads from river basin are largely affected by the interplay of climate variability and human activities within the basin. However, distinguishing the impacts of climate variability and human activities would vastly improve our knowledge of water resources, climate variability

  18. Lipid raft disarrangement as a result of neuropathological progresses: a novel strategy for early diagnosis?

    Science.gov (United States)

    Marin, R; Rojo, J A; Fabelo, N; Fernandez, C E; Diaz, M

    2013-08-15

    Lipid rafts are the preferential site of numerous membrane signaling proteins which are involved in neuronal functioning and survival. These proteins are organized in multiprotein complexes, or signalosomes, in close contact with lipid classes particularly represented in lipid rafts (i.e. cholesterol, sphingolipids and saturated fatty acids), which may contribute to physiological responses leading to neuroprotection. Increasing evidence indicates that alteration of lipid composition in raft structures as a consequence of neuropathologies, such as Alzheimer's disease (AD) and Parkinson's disease (PD), causes a dramatic increase in lipid raft order. These phenomena may correlate with perturbation of signalosome activities, likely contributing to neurodegenerative progression. Interestingly, significant disruption of stable raft microenvironments has been already observed in the first stages of either AD or PD, suggesting that these alterations may represent early events in the neuropathological development. In this regard, the search for biochemical markers, such as specific metabolic products altered in the brain at the first steps of the disease, presently represents an important challenge for early diagnostic strategies. Alterations of these biomarkers may be reflected in either plasma or cerebrospinal fluid, thus representing a potential strategy to predict an accurate diagnosis. We propose that pathologically-linked lipid raft markers may be interesting candidates to be explored at this level, although it has not been studied so far to what extent alteration of different signalosome components may be reflected in peripheral fluids. In this mini-review, we will discuss on relevant aspects of lipid rafts that contribute to the modulation of neuropathological events related to AD and PD. An interesting hypothesis is that anomalies on raft biomarkers measured at peripheral fluids might mirror the lipid raft pathology observed in early stages of AD and PD. Copyright

  19. Altered lysosome distribution is an early neuropathological event in neurological forms of Gaucher disease.

    Science.gov (United States)

    Zigdon, Hila; Meshcheriakova, Anna; Farfel-Becker, Tamar; Volpert, Giora; Sabanay, Helena; Futerman, Anthony H

    2017-03-01

    In the lysosomal storage disorder Gaucher disease (GD), glucosylceramide (GlcCer) accumulates due to the defective activity of glucocerebrosidase. A subset of GD patients develops neuropathology. We now show mislocalization of Limp2-positive puncta and a large reduction in the number of Lamp1-positive puncta, which are associated with impaired tubulin. These changes occur at an early stage in animal models of GD, prior to development of overt symptoms and considerably earlier than neuronal loss. Altered lysosomal localization and cytoskeleton disruption precede the neuroinflammatory pathways, axonal dystrophy and neuronal loss previously characterized in neuronal forms of GD. © 2017 Federation of European Biochemical Societies.

  20. Depression and Alzheimer's disease: is stress the initiating factor in a common neuropathological cascade?

    DEFF Research Database (Denmark)

    Aznar, Susana; Knudsen, Gitte M

    2011-01-01

    The existence of a high co-morbidity between Alzheimer's disease (AD) and depression has been known for a long time. More interesting though are recent studies indicating that depression and number of depressive episodes earlier in life is associated with increased risk of AD development....... This suggests the existence of common neuropathological mechanisms behind depression and AD. Here we propose that the brain changes associated with depressive episodes that compromise the brain's ability to cope with stress may constitute risk factors for development of AD. Furthermore, in individuals...... serotonergic and cholinergic system, hypothalamic-pituitary-adrenal axis and brain derived neurotrophic factor, and discussed in relation to AD....

  1. Creutzfeldt-Jacob-disease: The computerized tomogram in relation to clinical, electroencephalographic and neuropathological findings

    Energy Technology Data Exchange (ETDEWEB)

    Zieger, A.; Vonofakos, D.; Vitzthum, H.

    1981-12-01

    The computerized tomogram (CT) of a senile case of Creutzfeldt-Jacob disease with rapid progress, showed after an initially minor parietal dilatation of the gyri, a volume increase, predominantly on the right side, in the area of the cerebral convexity and a right-preponderant dilatation of the anterior horns. By neuropathologic examination indications for a passed cerebral oedema was found, covering the cortex atrophy, which previously had been detected by CT. Progression and local intensity of the atrophic signs in CT - in combination with clinical and electroencephalographic findings - suggest the existence of a Creutzfeldt-Jakob disease and permit its delineation against other atrophying processes.

  2. Creutzfeldt-Jacob-disease: The computerized tomogram in relation to clinical, electroencephalographic and neuropathological findings

    International Nuclear Information System (INIS)

    Zieger, A.

    1981-01-01

    The computerized tomogram (CT) of a senile case of Creutzfeldt-Jakob disease with rapid progress, showed after an initially minor parietal dilatation of the gyri, a volume increase, predominantly on the right side, in the area of the cerebral convexity and a right-preponderant dilatation of the anterior horns. By neuropathologic examination indications for a passed cerebral oedema was found, covering the cortex atrophy, which previously had been detected by CT. Progression and local intensity of the atrophic signs in CT - in combination with clinical and electroencephalographic findings - let appear probable the existence of a Creutzfeldt-Jakob disease and permit its delineation against other atrophying processes. (orig./MG) [de

  3. Conditional loss of progranulin in neurons is not sufficient to cause neuronal ceroid lipofuscinosis-like neuropathology in mice.

    Science.gov (United States)

    Petkau, Terri L; Blanco, Jake; Leavitt, Blair R

    2017-10-01

    Progranulin deficiency due to heterozygous null mutations in the GRN gene is a common cause of familial frontotemporal lobar degeneration (FTLD), while homozygous loss-of-function GRN mutations cause neuronal ceroid lipofuscinosis (NCL). Aged progranulin-knockout mice display highly exaggerated lipofuscinosis, microgliosis, and astrogliosis, as well as mild cell loss in specific brain regions. Progranulin is a secreted glycoprotein expressed in both neurons and microglia, but not astrocytes, in the brain. We generated conditional progranulin-knockout mice that lack progranulin in nestin-expressing cells (Nes-cKO mice), which include most neurons as well as astrocytes. We confirmed near complete knockout of progranulin in neurons in Nes-cKO mice, while microglial progranulin levels remained similar to that of wild-type animals. Overall brain progranulin levels were reduced by about 50% in Nes-cKO, and no Grn was detected in primary Nes-cKO neurons. Nes-cKO mice aged to 12months did not display any increase in lipofuscin deposition, microgliosis, or astrogliosis in the four brain regions examined, though increases were observed for most of these measures in Grn-null animals. We conclude that neuron-specific loss of progranulin is not sufficient to cause similar neuropathological changes to those seen in constitutive Grn-null animals. Our results suggest that increased lipofuscinosis and gliosis in Grn-null animals are not caused by intrinsic progranulin deficiency in neurons, and that microglia-derived progranulin may be sufficient to maintain neuronal health and homeostasis in the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Rhesus macaque and chimpanzee DC-SIGN act as HIV/SIV gp120 trans-receptors, similar to human DC-SIGN

    NARCIS (Netherlands)

    Geijtenbeek, T. B.; Koopman, G.; van Duijnhoven, G. C.; van Vliet, S. J.; van Schijndel, A. C.; Engering, A.; Heeney, J. L.; van Kooyk, Y.

    2001-01-01

    Dendritic cells (DC) have been implicated in the pathogenesis of both human and simian immunodeficiency viruses (HIV and SIV, respectively). The DC-specific HIV-1 trans-receptor DC-SIGN is thought to be essential for viral dissemination by DC. Abundant expression in lymphoid tissues also implies a

  5. Phylogenetic diversity and similarity of active sites of Shiga toxin (stx) in Shiga toxin-producing Escherichia coli (STEC) isolates from humans and animals.

    Science.gov (United States)

    Asakura, H; Makino, S; Kobori, H; Watarai, M; Shirahata, T; Ikeda, T; Takeshi, K

    2001-08-01

    Nucleotide sequences of Shiga toxin (Stx) genes in STEC from various origins were determined and characterized by phylogenetic analysis based on Shiga toxin (Stx) with those deposited in GenBank. The phylogenetic trees placed Stx1 and Stx2 into two and five groups respectively, and indicated that Stx1 in sheep-origin STEC were placed into a different group from those in other STEC, and that Stx2 of deer-origin STEC also belonged to the unique group and appeared to be distantly related to human-origin STEC. On the other hand, Stx of STEC isolated from cattle, seagulls and flies were closely related to those of human-origin STEC. Such a diversity of Stx suggested that STEC might be widely disseminated in many animal species, and be dependent on their host species or their habitat. In addition, the active sites in both toxins were compared; the active sites in both subunits of Stx in all the animal-origin STEC were identical to those in human-origin STEC, suggesting that all the toxin of STEC from animals might be also cytotoxic, and therefore, such animal-origin STEC might have potential pathogenicity for humans.

  6. Quantitative analysis of absorption, metabolism, and excretion of benzoxazinoids in humans after the consumption of high- and low-benzoxazinoid diets with similar contents of cereal dietary fibres

    DEFF Research Database (Denmark)

    Jensen, Bettina M; Adhikari, Khem B; Schnoor, Heidi J

    2017-01-01

    PURPOSE: Benzoxazinoids (BXs) are a group of wholegrain phytochemicals with potential pharmacological properties; however, limited information exists on their absorption, metabolism, and excretion in humans. The aim of this study was to investigate the dose-dependent uptake and excretion of dieta...

  7. Total calcium absorption is similar from infant formulas with and without prebiotics and exceeds that in human milk-fed infants

    Science.gov (United States)

    Our goal was to evaluate calcium absorption in infants fed a formula containing prebiotics (PF) and one without prebiotics (CF), and to compare calcium absorption from these formulas with a group of human milk-fed (HM) infants. A dual tracer stable isotope method was used to assess calcium absorptio...

  8. HOMOLOGY BETWEEN SEGMENTS OF HUMAN HEMOSTATIC PROTEINS AND PROTEINS OF VIRUSES WHICH CAUSE ACUTE RESPIRATORY INFECTIONS OR DISEASES WITH SIMILAR SYMPTOMS

    Directory of Open Access Journals (Sweden)

    I. N. Zhilinskaya

    2017-01-01

    Full Text Available Objectives: To identify homologous segments of human hemostatic and viral proteins and to assess the role of human hemostatic proteins in viral replication. Materials and Methods: The following viruses were chosen for comparison: influenza B (B/Astrakhan/2/2017, coronaviruses (Hcov229E and SARS-Co, type 1 adenovirus (adenoid 71, measles (ICHINOSE-BA and rubella (Therien. The primary structures of viral proteins and 41 human hemostatic proteins were obtained from open–access www.ncbi.nlm.nih. gov and www.nextprot.org databases, respectively. Sequence homology was determined by comparing 12-amino-acid segments. Those sequences identical in ≥ 8 positions were considered homologous. Results: The analysis shows that viral proteins contain segments which mimic a number of human hemostatic proteins. Most of these segments, except those of adenovirus proteins, are homologous with coagulation factors. The increase in viral virulence, as in case of SARS-Co, correlates with an increased number of segments homologous with hemostatic proteins. Conclusion: Hemostasis plays an important role in viral replication and pathogenesis. The conclusion is consistent with the literature data about the relationship of hemostasis and inflammatory response to viral infections.

  9. Similar or different?

    DEFF Research Database (Denmark)

    Cornér, Solveig; Pyhältö, Kirsi; Peltonen, Jouni

    2018-01-01

    Previous research has identified researcher community and supervisory support as key determinants of the doctoral journey contributing to students’ persistence and robustness. However, we still know little about cross-cultural variation in the researcher community and supervisory support experien...... counter partners, whereas the Finnish students perceived lower levels of instrumental support than the Danish students. The findings imply that seemingly similar contexts hold valid differences in experienced social support and educational strategies at the PhD level....... experienced by PhD students within the same discipline. This study explores the support experiences of 381 PhD students within the humanities and social sciences from three research-intensive universities in Denmark (n=145) and Finland (n=236). The mixed methods design was utilized. The data were collected...... counter partners. The results also indicated that the only form of support in which the students expressed more matched support than mismatched support was informational support. Further investigation showed that the Danish students reported a high level of mismatch in emotional support than their Finnish...

  10. A COMPARISON OF SEMANTIC SIMILARITY MODELS IN EVALUATING CONCEPT SIMILARITY

    Directory of Open Access Journals (Sweden)

    Q. X. Xu

    2012-08-01

    Full Text Available The semantic similarities are important in concept definition, recognition, categorization, interpretation, and integration. Many semantic similarity models have been established to evaluate semantic similarities of objects or/and concepts. To find out the suitability and performance of different models in evaluating concept similarities, we make a comparison of four main types of models in this paper: the geometric model, the feature model, the network model, and the transformational model. Fundamental principles and main characteristics of these models are introduced and compared firstly. Land use and land cover concepts of NLCD92 are employed as examples in the case study. The results demonstrate that correlations between these models are very high for a possible reason that all these models are designed to simulate the similarity judgement of human mind.

  11. Invited review: Frontotemporal dementia caused by microtubule-associated protein tau gene (MAPT) mutations: a chameleon for neuropathology and neuroimaging.

    Science.gov (United States)

    Ghetti, B; Oblak, A L; Boeve, B F; Johnson, K A; Dickerson, B C; Goedert, M

    2015-02-01

    Hereditary frontotemporal dementia associated with mutations in the microtubule-associated protein tau gene (MAPT) is a protean disorder. Three neuropathologic subtypes can be recognized, based on the presence of inclusions made of tau isoforms with three and four repeats, predominantly three repeats and mostly four repeats. This is relevant for establishing a correlation between structural magnetic resonance imaging and positron emission tomography using tracers specific for aggregated tau. Longitudinal studies will be essential to determine the evolution of anatomical alterations from the asymptomatic stage to the various phases of disease following the onset of symptoms. © 2014 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

  12. Progression of regional neuropathology in Alzheimer disease and normal elderly: findings from the Nun study.

    Science.gov (United States)

    Wolf, D S; Gearing, M; Snowdon, D A; Mori, H; Markesbery, W R; Mirra, S S

    1999-01-01

    Although diffuse plaques in the neocortex may represent an early stage in the evolution of neuritic plaques, plaques in the striatum and cerebellum retain their predominantly diffuse nature in Alzheimer disease (AD), regardless of disease duration. We had the opportunity to explore the progression of these regional features by using autopsy brain specimens from 15 cognitively normal and five AD subjects, all Catholic sisters enrolled in the Nun Study, a longitudinal study on aging and AD. Neuropathologic changes were assessed in the temporal cortex, striatum, and cerebellum without knowledge of clinical status. We found diffuse plaques in the striatum in six (40%) and cerebellar plaques in none of the brains from the non-demented subjects. Striatal plaques were present in all five and cerebellar plaques in four of the five AD cases. In the 20 cases overall, the presence of striatal plaques generally paralleled the occurrence of neuritic plaques in neocortex and correlated with lower scores on several neuropsychologic tests assessing memory. Our findings suggest that striatal diffuse plaques occur relatively early in the progression of AD pathology and coincide with neocortical pathology and cognitive changes. Thus, it is unlikely that temporal factors alone account for regional differences in progression of AD neuropathology.

  13. Convection-enhanced drug delivery to the brain: therapeutic potential and neuropathological considerations.

    Science.gov (United States)

    Barua, Neil U; Gill, Steven S; Love, Seth

    2014-03-01

    Convection-enhanced delivery (CED) describes a direct method of drug delivery to the brain through intraparenchymal microcatheters. By establishing a pressure gradient at the tip of the infusion catheter in order to exploit bulk flow through the interstitial spaces of the brain, CED offers a number of advantages over conventional drug delivery methods-bypass of the blood-brain barrier, targeted distribution through large brain volumes and minimization of systemic side effects. Despite showing early promise, CED is yet to fulfill its potential as a mainstream strategy for the treatment of neurological disease. Substantial research effort has been dedicated to optimize the technology for CED and identify the parameters, which govern successful drug distribution. It seems likely that successful clinical translation of CED will depend on suitable catheter technology being used in combination with drugs with optimal physicochemical characteristics, and on neuropathological analysis in appropriate preclinical models. In this review, we consider the factors most likely to influence the success or failure of CED, and review its application to the treatment of high-grade glioma, Parkinson's disease (PD) and Alzheimer's disease (AD). © 2013 International Society of Neuropathology.

  14. Reducing GBA2 Activity Ameliorates Neuropathology in Niemann-Pick Type C Mice.

    Directory of Open Access Journals (Sweden)

    André R A Marques

    Full Text Available The enzyme glucocerebrosidase (GBA hydrolyses glucosylceramide (GlcCer in lysosomes. Markedly reduced GBA activity is associated with severe manifestations of Gaucher disease including neurological involvement. Mutations in the GBA gene have recently also been identified as major genetic risk factor for Parkinsonism. Disturbed metabolism of GlcCer may therefore play a role in neuropathology. Besides lysosomal GBA, cells also contain a non-lysosomal glucosylceramidase (GBA2. Given that the two β-glucosidases share substrates, we speculated that over-activity of GBA2 during severe GBA impairment might influence neuropathology. This hypothesis was studied in Niemann-Pick type C (Npc1-/- mice showing secondary deficiency in GBA in various tissues. Here we report that GBA2 activity is indeed increased in the brain of Npc1-/- mice. We found that GBA2 is particularly abundant in Purkinje cells (PCs, one of the most affected neuronal populations in NPC disease. Inhibiting GBA2 in Npc1-/- mice with a brain-permeable low nanomolar inhibitor significantly improved motor coordination and extended lifespan in the absence of correction in cholesterol and ganglioside abnormalities. This trend was recapitulated, although not to full extent, by introducing a genetic loss of GBA2 in Npc1-/- mice. Our findings point to GBA2 activity as therapeutic target in NPC.

  15. The Effect of Vascular Neuropathology on Late-life Cognition: Results from the SMART Project.

    Science.gov (United States)

    Kryscio, R J; Abner, E L; Nelson, P T; Bennett, D; Schneider, J; Yu, L; Hemmy, L S; Lim, K O; Masaki, K; Cairns, N; Xiong, C; Woltjer, R; Dodge, H H; Tyas, S; Fardo, D W; Lou, W; Wan, L; Schmitt, F A

    2016-06-01

    Cerebral vascular pathology may contribute to cognitive decline experienced by some elderly near death. Given evidence for mixed neuropathologies in advanced age, preventing or reducing cerebrovascular burden in late life may be beneficial. To correlate measures of cerebral vascular pathology with cognitive trajectories. Observational study. A cohort of 2,274 individuals who came to autopsy at a mean age of 89.3 years and 82 percent of whom had at least two cognitive assessments within the last six years of life was compiled from six centers conducting longitudinal studies. For each cognitive domain: immediate and delayed memory, language, and naming, three trajectories were examined: good, intermediate, and poor cognition. The probability of a participant belonging to each trajectory was associated with measures of cerebral vascular pathology after adjustment for demographics, APOE, and Alzheimer neuropathology. A large proportion of the cohort (72-94%) experienced good or intermediate cognition in the four domains examined. The presence of arteriolosclerosis and the presence of lacunar infarcts doubled the odds of belonging to the poor cognitive trajectory for language when compared to the good trajectory. The presence of lacunar infarcts increased the odds of an intermediate or poor trajectory for immediate and delayed recall while the presence of large artery infarcts increased the odds of poor trajectories for all four cognitive domains examined. Microinfarcts and cerebral amyloid angiopathy had little effect on the trajectories. Indicators of cerebral vascular pathology act differently on late life cognition.

  16. Neuropathology of the recessive A673V APP mutation: Alzheimer disease with distinctive features.

    Science.gov (United States)

    Giaccone, Giorgio; Morbin, Michela; Moda, Fabio; Botta, Mario; Mazzoleni, Giulia; Uggetti, Andrea; Catania, Marcella; Moro, Maria Luisa; Redaelli, Veronica; Spagnoli, Alberto; Rossi, Roberta Simona; Salmona, Mario; Di Fede, Giuseppe; Tagliavini, Fabrizio

    2010-12-01

    Mutations of three different genes, encoding β-amyloid precursor protein (APP), presenilin 1 and presenilin 2 are associated with familial Alzheimer's disease (AD). Recently, the APP mutation A673V has been identified that stands out from all the genetic defects previously reported in these three genes, since it causes the disease only in the homozygous state (Di Fede et al. in Science 323:1473-1477, 2009). We here provide the detailed neuropathological picture of the proband of this family, who was homozygous for the APP A673V mutation and recently came to death. The brain has been studied by histological and immunohistochemical techniques, at the optical and ultrastructural levels. Cerebral Aβ accumulation and tau pathology were severe and extensive. Peculiar features were the configuration of the Aβ deposits that were of large size, mostly perivascular and exhibited a close correspondence between the pattern elicited by amyloid stainings and the labeling obtained with immunoreagents specific for Aβ40 or Aβ42. Moreover, Aβ deposition spared the neostriatum while deeply affecting the cerebellum, and therefore was not in compliance with the hierarchical topographical sequence of involvement documented in sporadic AD. Therefore, the neuropathological picture of familial AD caused by the APP recessive mutation A673V presents distinctive characteristics compared to sporadic AD or familial AD inherited as a dominant trait. Main peculiar features are the morphology, structural properties and composition of the Aβ deposits as well as their topographic distribution in the brain.

  17. Type III secretion system and virulence markers highlight similarities and differences between human- and plant-associated Pseudomonads related to Pseudomonas fluorescens and P-putida

    OpenAIRE

    Mazurier, Sylvie; Merieau, Annabelle; Bergeau, Dorian; Decoin, Victorien; Sperandio, Daniel; Crepin, Alexandre; Barbey, Corinne; Jeannot, Katy; Vicre-Gibouin, Maité; Plesiat, Patrick; Lemanceau, Philippe; Latour, Xavier

    2015-01-01

    Pseudomonas fluorescens is commonly considered a saprophytic rhizobacterium devoid of pathogenic potential. Nevertheless, the recurrent isolation of strains from clinical human cases could indicate the emergence of novel strains originating from the rhizosphere reservoir, which could be particularly resistant to the immune system and clinical treatment. The importance of type three secretion systems (T3SSs) in the related Pseudomonas aeruginosa nosocomial species and the occurrence of this se...

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

    Science.gov (United States)

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

    2016-08-30

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

  19. A Study Similarities and Differences in Selected Human Resource Practices and Their Relation to Teacher Retention in a Sample of Four School Districts, Two with High and Two with Low Rates of Retention

    Science.gov (United States)

    Phelan, Patrick M.

    2010-01-01

    This is a study of the practices utilized by four school districts, two with high and two with low retention rates of teachers, to examine how similarities and differences in selected human resources practices relate to the successful retention of teachers in these districts. The factors studied that may impact teacher retention included…

  20. High similarity of phylogenetic profiles of rate-limiting enzymes with inhibitory relation in Human, Mouse, Rat, budding Yeast and E. coli.

    Science.gov (United States)

    Zhao, Min; Qu, Hong

    2011-11-30

    The phylogenetic profile is widely used to characterize functional linkage and conservation between proteins without amino acid sequence similarity. To survey the conservative regulatory properties of rate-limiting enzymes (RLEs) in metabolic inhibitory network across different species, we define the enzyme inhibiting pair as: where the first enzyme in a pair is the inhibitor provider and the second is the target of the inhibitor. Phylogenetic profiles of enzymes in the inhibiting pairs are further generated to measure the functional linkage of these enzymes during evolutionary history. We find that the RLEs generate, on average, over half of all in vivo inhibitors in each surveyed model organism. And these inhibitors inhibit on average over 85% targets in metabolic inhibitory network and cover the majority of targets of cross-pathway inhibiting relations. Furthermore, we demonstrate that the phylogenetic profiles of the enzymes in inhibiting pairs in which at least one enzyme is rate-limiting often show higher similarities than those in common inhibiting enzyme pairs. In addition, RLEs, compared to common metabolic enzymes, often tend to produce ADP instead of AMP in conservative inhibitory networks. Combined with the conservative roles of RLEs in their efficiency in sensing metabolic signals and transmitting regulatory signals to the rest of the metabolic system, the RLEs may be important molecules in balancing energy homeostasis via maintaining the ratio of ATP to ADP in living cells. Furthermore, our results indicate that similarities of phylogenetic profiles of enzymes in the inhibiting enzyme pairs are not only correlated with enzyme topological importance, but also related with roles of the enzymes in metabolic inhibitory network.

  1. Overlapping trisomies for human chromosome 21 orthologs produce similar effects on skull and brain morphology of Dp(16)1Yey and Ts65Dn mice.

    Science.gov (United States)

    Starbuck, John M; Dutka, Tara; Ratliff, Tabetha S; Reeves, Roger H; Richtsmeier, Joan T

    2014-08-01

    Trisomy 21 results in gene-dosage imbalance during embryogenesis and throughout life, ultimately causing multiple anomalies that contribute to the clinical manifestations of Down syndrome. Down syndrome is associated with manifestations of variable severity (e.g., heart anomalies, reduced growth, dental anomalies, shortened life-span). Craniofacial dysmorphology and cognitive dysfunction are consistently observed in all people with Down syndrome. Mouse models are useful for studying the effects of gene-dosage imbalance on development. We investigated quantitative changes in the skull and brain of the Dp(16)1Yey Down syndrome mouse model and compared these mice to Ts65Dn and Ts1Cje mouse models. Three-dimensional micro-computed tomography images of Dp(16)1Yey and euploid mouse crania were morphometrically evaluated. Cerebellar cross-sectional area, Purkinje cell linear density, and granule cell density were evaluated relative to euploid littermates. Skulls of Dp(16)1Yey and Ts65Dn mice displayed similar changes in craniofacial morphology relative to their respective euploid littermates. Trisomy-based differences in brain morphology were also similar in Dp(16)1Yey and Ts65Dn mice. These results validate examination of the genetic basis for craniofacial and brain phenotypes in Dp(16)1Yey mice and suggest that they, like Ts65Dn mice, are valuable tools for modeling the effects of trisomy 21 on development. © 2014 Wiley Periodicals, Inc.

  2. New Similarity Functions

    DEFF Research Database (Denmark)

    Yazdani, Hossein; Ortiz-Arroyo, Daniel; Kwasnicka, Halina

    2016-01-01

    spaces, in addition to their similarity in the vector space. Prioritized Weighted Feature Distance (PWFD) works similarly as WFD, but provides the ability to give priorities to desirable features. The accuracy of the proposed functions are compared with other similarity functions on several data sets....... Our results show that the proposed functions work better than other methods proposed in the literature....

  3. Phoneme Similarity and Confusability

    Science.gov (United States)

    Bailey, T.M.; Hahn, U.

    2005-01-01

    Similarity between component speech sounds influences language processing in numerous ways. Explanation and detailed prediction of linguistic performance consequently requires an understanding of these basic similarities. The research reported in this paper contrasts two broad classes of approach to the issue of phoneme similarity-theoretically…

  4. The cyanobacterial bicarbonate transporter BicA: its physiological role and the implications of structural similarities with human SLC26 transporters.

    Science.gov (United States)

    Price, G Dean; Howitt, Susan M

    2011-04-01

    The cyanobacterial Na+-dependent HCO3- transporter BicA is a member of the ubiquitous and important SulP/SLC26 family of anion transporters found in eukaryotes and prokaryotes. BicA is an important component of the cyanobacterial CO2 concentrating mechanism, an adaptation that contributes to cyanobacteria being able to achieve an estimated 25% of global primary productivity, largely in the oceans. The human SLC26 members are involved in a range of key cellular functions involving a diverse range of anion transport activities including Cl-/HCO3-, I-/HCO3-, and SO42-/HCO3- exchange; mutations in SLC26 members are known to be associated with debilitating diseases such as Pendred syndrome, chondrodysplasias, and congenital chloride diarrhoea. We have recently experimentally determined the membrane topology of BicA using the phoA-lacZ reporter system and here consider some of the extrapolated implications for topology of the human SLC26 family and the Sultr plant sulphate transporters.

  5. Patient with rapidly evolving neurological disease with neuropathological lesions of Creutzfeldt-Jakob disease, Lewy body dementia, chronic subcortical vascular encephalopathy and meningothelial meningioma.

    Science.gov (United States)

    Vita, Maria Gabriella; Tiple, Dorina; Bizzarro, Alessandra; Ladogana, Anna; Colaizzo, Elisa; Capellari, Sabina; Rossi, Marcello; Parchi, Piero; Masullo, Carlo; Pocchiari, Maurizio

    2017-04-01

    We report a case of rapidly evolving neurological disease in a patient with neuropathological lesions of Creutzfeldt-Jakob disease (CJD), Lewy body dementia (LBD), chronic subcortical vascular encephalopathy and meningothelial meningioma. The coexistence of severe multiple pathologies in a single patient strengthens the need to perform accurate clinical differential diagnoses in rapidly progressive dementias. © 2016 Japanese Society of Neuropathology.

  6. Sub-Chronic Neuropathological and Biochemical Changes in Mouse Visual System after Repetitive Mild Traumatic Brain Injury.

    Directory of Open Access Journals (Sweden)

    Radouil Tzekov

    Full Text Available Repetitive mild traumatic brain injury (r-mTBI results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC number, while optic nerve tissue was examined for cellularity, myelin content, protein and lipid changes. Increased cellularity and areas of demyelination were clearly detectable in optic nerves in r-mTBI, but not in r-sham. These changes were accompanied by a ~25% decrease in the total number of Brn3a-positive RGCs. Proteomic analysis of the optic nerves demonstrated various changes consistent with a negative effect of r-mTBI on major cellular processes like depolymerization of microtubules, disassembly of filaments and loss of neurons, manifested by decrease of several proteins, including neurofilaments (NEFH, NEFM, NEFL, tubulin (TUBB2A, TUBA4A, microtubule-associated proteins (MAP1A, MAP1B, collagen (COL6A1, COL6A3 and increased expression of other proteins, including heat shock proteins (HSP90B1, HSPB1, APOE and cathepsin D. Lipidomic analysis showed quantitative changes in a number of phospholipid species, including a significant increase in the total amount of lysophosphatidylcholine (LPC, including the molecular species 16:0, a known demyelinating agent. The overall amount of some ether phospholipids, like ether LPC, ether phosphatidylcholine and ether lysophosphatidylethanolamine were also increased, while the majority of individual molecular species of ester phospholipids, like phosphatidylcholine and phosphatidylethanolamine, were decreased. Results from the biochemical analysis correlate well with changes detected by histological and immunohistochemical methods and indicate the

  7. Human circulating monocytes internalize 125I-insulin in a similar fashion to rat hepatocytes: relevance to receptor regulation in target and nontarget tissues

    International Nuclear Information System (INIS)

    Grunberger, G.; Robert, A.; Carpentier, J.L.; Dayer, J.M.; Roth, A.; Stevenson, H.C.; Orci, L.; Gorden, P.

    1985-01-01

    Circulating monocytes bind 125 I-insulin in a specific fashion and have been used to analyze the ambient receptor status in humans. When freshly isolated circulating monocytes are incubated with 125 I-insulin and examined by electron microscopic autoradiography, approximately 18% of the labeled material is internalized after 15 minutes at 37 degrees C. By 2 hours at 37 degrees C, approximately one half of the 125 I-insulin is internalized. Internalization occurs also at 15 degrees C but at a slower rate. Furthermore, the monocytes bind and internalize 125 I-insulin in a manner that mirrors that of major target tissues, such as rat hepatocytes. These data suggest that the insulin receptor of the circulating monocyte might be regulated by adsorptive endocytosis in a manner analogous to that of target tissue, such as the liver

  8. How similar are fluid cognition and general intelligence? A developmental neuroscience perspective on fluid cognition as an aspect of human cognitive ability.

    Science.gov (United States)

    Blair, Clancy

    2006-04-01

    This target article considers the relation of fluid cognitive functioning to general intelligence. A neurobiological model differentiating working memory/executive function cognitive processes of the prefrontal cortex from aspects of psychometrically defined general intelligence is presented. Work examining the rise in mean intelligence-test performance between normative cohorts, the neuropsychology and neuroscience of cognitive function in typically and atypically developing human populations, and stress, brain development, and corticolimbic connectivity in human and nonhuman animal models is reviewed and found to provide evidence of mechanisms through which early experience affects the development of an aspect of cognition closely related to, but distinct from, general intelligence. Particular emphasis is placed on the role of emotion in fluid cognition and on research indicating fluid cognitive deficits associated with early hippocampal pathology and with dysregulation of the hypothalamic-pituitary-adrenal axis stress-response system. Findings are seen to be consistent with the idea of an independent fluid cognitive construct and to assist with the interpretation of findings from the study of early compensatory education for children facing psychosocial adversity and from behavior genetic research on intelligence. It is concluded that ongoing development of neurobiologically grounded measures of fluid cognitive skills appropriate for young children will play a key role in understanding early mental development and the adaptive success to which it is related, particularly for young children facing social and economic disadvantage. Specifically, in the evaluation of the efficacy of compensatory education efforts such as Head Start and the readiness for school of children from diverse backgrounds, it is important to distinguish fluid cognition from psychometrically defined general intelligence.

  9. Effects of similar intakes of marine n-3 fatty acids from enriched food products and fish oil on cardiovascular risk markers in healthy human subjects.

    Science.gov (United States)

    Kirkhus, Bente; Lamglait, Amandine; Eilertsen, Karl-Erik; Falch, Eva; Haider, Trond; Vik, Hogne; Hoem, Nils; Hagve, Tor-Arne; Basu, Samar; Olsen, Elisabeth; Seljeflot, Ingebjørg; Nyberg, Lena; Elind, Elisabeth; Ulven, Stine M

    2012-05-01

    There is convincing evidence that consumption of fish and fish oil rich in long-chain (LC) n-3 PUFA (n-3 LCPUFA), EPA (20 : 5n-3) and DHA (22 : 6n-3) reduce the risk of CHD. The aim of the present study was to investigate whether n-3 LCPUFA-enriched food products provide similar beneficial effects as fish oil with regard to incorporation into plasma lipids and effects on cardiovascular risk markers. A parallel 7-week intervention trial was performed where 159 healthy men and women were randomised to consume either 34 g fish pâté (n 44), 500 ml fruit juice (n 38) or three capsules of concentrated fish oil (n 40), all contributing to a daily intake of approximately 1 g EPA and DHA. A fourth group did not receive any supplementation or food product and served as controls (n 37). Plasma fatty acid composition, serum lipids, and markers of inflammation and oxidative stress were measured. Compared with the control group, plasma n-3 LCPUFA and EPA:arachidonic acid ratio increased equally in all intervention groups. However, no significant changes in blood lipids and markers of inflammation and oxidative stress were observed. In conclusion, enriched fish pâté and fruit juice represent suitable delivery systems for n-3 LCPUFA. However, although the dose given is known to reduce the risk of CVD, no significant changes were observed on cardiovascular risk markers in this healthy population.

  10. Patterns of some extracellular matrix gene expression are similar in cells from cleft lip-palate patients and in human palatal fibroblasts exposed to diazepam in culture

    International Nuclear Information System (INIS)

    Marinucci, Lorella; Balloni, Stefania; Bodo, Maria; Carinci, Francesco; Pezzetti, Furio; Stabellini, Giordano; Carmela, Conte; Lumare, Eleonora

    2009-01-01

    Prenatal exposure to diazepam, a prototype sedative drug that belongs to Benzodiazepines, can lead to orofacial clefting in human newborns. By using real-time PCR, in the present study we investigated whether diazepam elicits gene expression alterations in extracellular matrix (ECM) components, growth factors and gamma-aminobutyric acid receptor (GABRB3), implicated in the coordinate regulation of palate development. Palate fibroblasts were treated with diazepam (Dz-N fibroblasts) and compared to cleft lip-palate (CLP) fibroblasts obtained from patients with no known exposure to diazepam or other teratogens. Untreated fibroblasts from non-CLP patients were used as control. The results showed significant convergences in gene expression pattern of collagens, fibromodulin, vitronectin, tenascin C, integrins and metalloprotease MMP13 between Dz-N and CLP fibroblasts. Among the growth factors, constitutive Fibroblast Growth Factor 2 (FGF2) was greatly enhanced in Dz-N and CLP fibroblasts and associated with a higher reduction of FGF receptor. Transforming Growth Factor beta 3 (TGFβ 3 ) resulted up-regulated in CLP fibroblasts and decreased in Dz-N fibroblasts. We found phenotypic differences exhibited by Dz-N and CLP fibroblasts in GABRB3 gene regulation, so further studies are necessary to determine whether GABAergic system could be involved in the development of diazepam mediated CLP phenotype. Taken together the results elucidate the molecular mechanisms underlying possible toxicology effects induced by diazepam. Counselling of women on the safety of diazepam exposure is clinically important, also for the forensic consequences

  11. Molecular similarity measures.

    Science.gov (United States)

    Maggiora, Gerald M; Shanmugasundaram, Veerabahu

    2011-01-01

    Molecular similarity is a pervasive concept in chemistry. It is essential to many aspects of chemical reasoning and analysis and is perhaps the fundamental assumption underlying medicinal chemistry. Dissimilarity, the complement of similarity, also plays a major role in a growing number of applications of molecular diversity in combinatorial chemistry, high-throughput screening, and related fields. How molecular information is represented, called the representation problem, is important to the type of molecular similarity analysis (MSA) that can be carried out in any given situation. In this work, four types of mathematical structure are used to represent molecular information: sets, graphs, vectors, and functions. Molecular similarity is a pairwise relationship that induces structure into sets of molecules, giving rise to the concept of chemical space. Although all three concepts - molecular similarity, molecular representation, and chemical space - are treated in this chapter, the emphasis is on molecular similarity measures. Similarity measures, also called similarity coefficients or indices, are functions that map pairs of compatible molecular representations that are of the same mathematical form into real numbers usually, but not always, lying on the unit interval. This chapter presents a somewhat pedagogical discussion of many types of molecular similarity measures, their strengths and limitations, and their relationship to one another. An expanded account of the material on chemical spaces presented in the first edition of this book is also provided. It includes a discussion of the topography of activity landscapes and the role that activity cliffs in these landscapes play in structure-activity studies.

  12. The role of neuropathological markers in the interpretation of neuropsychiatric disorders: Focus on fetal and perinatal programming.

    Science.gov (United States)

    Fanni, Daniela; Gerosa, Clara; Rais, Monica; Ravarino, Alberto; Van Eyken, Peter; Fanos, Vassilios; Faa, Gavino

    2018-03-16

    The study of neuropathological markers in patients affected by mental/psychiatric disorders is relevant for the comprehension of the pathogenesis and the correlation with the clinical symptomatology. The neuropathology of Alzheimer's disease (AD) recognizes intraneuronal and extracellular neurofibrillary formation responsible for neuronal degeneration. Immunohistochemical studies discovered many interesting results for a better interpretation of the AD pathogenesis, while the "metal hypothesis" supports that metal ions might differentially influence the formation of amyloid aggregates. The most relevant pathological findings reported in schizophrenia originate from computer assisted tomography (CT), Magnetic Resonance Imaging (MRI) studies and Diffusion Tensor Imaging (DTI), suggesting the brain abnormalities involved in the pathophysiology of schizophrenia. The theory of fetal programming illustrates the epigenetic factors that may act during the intrauterine life on brain development, with relevant consequences on the susceptibility to develop AD or schizophrenia later in life. The neuropathological interpretation of AD and schizophrenia shows that the presence of severe neuropathological changes is not always associated with severe cognitive impairment. A better dialogue between psychiatrics and pathologists might help to halt insurgence and progression of neurodegenerative diseases. Copyright © 2016. Published by Elsevier B.V.

  13. MRI in sporadic Creutzfeldt-Jakob disease: Correlation with clinical and neuropathological data

    Energy Technology Data Exchange (ETDEWEB)

    Urbach, H.; Solymosi, L. [Department of Neuroradiology, University of Wuerzburg (Germany); Klisch, J.; Brechtelsbauer, D. [Department of Neuroradiology, University of Bonn, Bonn (Germany); Wolf, H.K. [Department of Neuropathology, University of Bonn, Bonn (Germany); Gass, S. [Department of Neurology, University of Bonn, Bonn (Germany)

    1998-02-01

    To ascertain whether increased grey matter signal intensity on T2-weighted images in patients with sporadic Creutzfeldt-Jakob disease (CJD) corresponds to the stage and severity of this disease, we correlated MRI findings in four of our own and previously reported patients with sporadic CJD with the clinical variants, neuropathological changes at autopsy, duration of the disease and survival time after MRI examination. Of 15 patients with the extrapyramidal type of CJD, 10 showed increased signal in the basal ganglia on T2-weighted images. One of seven patients with the Heidenhain variant had increased signal in the occipital cortex. Patients without increased grey matter signal intensity had a longer overall duration of CJD (P = 0.035). Although the interval between onset of neurological symptoms and MRI was not different, patients without increased grey matter signal also survived longer after MRI examination (P = 0.022). (orig.) With 5 figs., 2 tabs., 23 refs.

  14. MRI in sporadic Creutzfeldt-Jakob disease: Correlation with clinical and neuropathological data

    International Nuclear Information System (INIS)

    Urbach, H.; Solymosi, L.; Klisch, J.; Brechtelsbauer, D.; Wolf, H.K.; Gass, S.

    1998-01-01

    To ascertain whether increased grey matter signal intensity on T2-weighted images in patients with sporadic Creutzfeldt-Jakob disease (CJD) corresponds to the stage and severity of this disease, we correlated MRI findings in four of our own and previously reported patients with sporadic CJD with the clinical variants, neuropathological changes at autopsy, duration of the disease and survival time after MRI examination. Of 15 patients with the extrapyramidal type of CJD, 10 showed increased signal in the basal ganglia on T2-weighted images. One of seven patients with the Heidenhain variant had increased signal in the occipital cortex. Patients without increased grey matter signal intensity had a longer overall duration of CJD (P = 0.035). Although the interval between onset of neurological symptoms and MRI was not different, patients without increased grey matter signal also survived longer after MRI examination (P = 0.022). (orig.)

  15. Depression and Alzheimer's disease: is stress the initiating factor in a common neuropathological cascade?

    DEFF Research Database (Denmark)

    Aznar, Susana; Knudsen, Gitte M

    2011-01-01

    . This suggests the existence of common neuropathological mechanisms behind depression and AD. Here we propose that the brain changes associated with depressive episodes that compromise the brain's ability to cope with stress may constitute risk factors for development of AD. Furthermore, in individuals......The existence of a high co-morbidity between Alzheimer's disease (AD) and depression has been known for a long time. More interesting though are recent studies indicating that depression and number of depressive episodes earlier in life is associated with increased risk of AD development...... with a genetic linkage to depression, there may be an increased vulnerability towards the initiation of a detrimental neurodegenerative cascade. The following review will deal with the various observations reported within the different neurobiological systems known to be involved and affected in depression, like...

  16. Mutations in the Caenorhabditis elegans orthologs of human genes required for mitochondrial tRNA modification cause similar electron transport chain defects but different nuclear responses.

    Science.gov (United States)

    Navarro-González, Carmen; Moukadiri, Ismaïl; Villarroya, Magda; López-Pascual, Ernesto; Tuck, Simon; Armengod, M-Eugenia

    2017-07-01

    Several oxidative phosphorylation (OXPHOS) diseases are caused by defects in the post-transcriptional modification of mitochondrial tRNAs (mt-tRNAs). Mutations in MTO1 or GTPBP3 impair the modification of the wobble uridine at position 5 of the pyrimidine ring and cause heart failure. Mutations in TRMU affect modification at position 2 and cause liver disease. Presently, the molecular basis of the diseases and why mutations in the different genes lead to such different clinical symptoms is poorly understood. Here we use Caenorhabditis elegans as a model organism to investigate how defects in the TRMU, GTPBP3 and MTO1 orthologues (designated as mttu-1, mtcu-1, and mtcu-2, respectively) exert their effects. We found that whereas the inactivation of each C. elegans gene is associated with a mild OXPHOS dysfunction, mutations in mtcu-1 or mtcu-2 cause changes in the expression of metabolic and mitochondrial stress response genes that are quite different from those caused by mttu-1 mutations. Our data suggest that retrograde signaling promotes defect-specific metabolic reprogramming, which is able to rescue the OXPHOS dysfunction in the single mutants by stimulating the oxidative tricarboxylic acid cycle flux through complex II. This adaptive response, however, appears to be associated with a biological cost since the single mutant worms exhibit thermosensitivity and decreased fertility and, in the case of mttu-1, longer reproductive cycle. Notably, mttu-1 worms also exhibit increased lifespan. We further show that mtcu-1; mttu-1 and mtcu-2; mttu-1 double mutants display severe growth defects and sterility. The animal models presented here support the idea that the pathological states in humans may initially develop not as a direct consequence of a bioenergetic defect, but from the cell's maladaptive response to the hypomodification status of mt-tRNAs. Our work highlights the important association of the defect-specific metabolic rewiring with the pathological phenotype

  17. Type III secretion system and virulence markers highlight similarities and differences between human- and plant-associated pseudomonads related to Pseudomonas fluorescens and P. putida.

    Science.gov (United States)

    Mazurier, Sylvie; Merieau, Annabelle; Bergeau, Dorian; Decoin, Victorien; Sperandio, Daniel; Crépin, Alexandre; Barbey, Corinne; Jeannot, Katy; Vicré-Gibouin, Maïté; Plésiat, Patrick; Lemanceau, Philippe; Latour, Xavier

    2015-04-01

    Pseudomonas fluorescens is commonly considered a saprophytic rhizobacterium devoid of pathogenic potential. Nevertheless, the recurrent isolation of strains from clinical human cases could indicate the emergence of novel strains originating from the rhizosphere reservoir, which could be particularly resistant to the immune system and clinical treatment. The importance of type three secretion systems (T3SSs) in the related Pseudomonas aeruginosa nosocomial species and the occurrence of this secretion system in plant-associated P. fluorescens raise the question of whether clinical isolates may also harbor T3SSs. In this study, isolates associated with clinical infections and identified in hospitals as belonging to P. fluorescens were compared with fluorescent pseudomonads harboring T3SSs isolated from plants. Bacterial isolates were tested for (i) their genetic relationships based on their 16S rRNA phylogeny, (ii) the presence of T3SS genes by PCR, and (iii) their infectious potential on animals and plants under environmental or physiological temperature conditions. Two groups of bacteria were delineated among the clinical isolates. The first group encompassed thermotolerant (41°C) isolates from patients suffering from blood infections; these isolates were finally found to not belong to P. fluorescens but were closely related and harbored highly conserved T3SS genes belonging to the Ysc-T3SS family, like the T3SSs from P. aeruginosa. The second group encompassed isolates from patients suffering from cystic fibrosis; these isolates belonged to P. fluorescens and harbored T3SS genes belonging to the Hrp1-T3SS family found commonly in plant-associated P. fluorescens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. Neuropathological survey reveals underestimation of the prevalence of neuroinfectious diseases in cattle in Switzerland.

    Science.gov (United States)

    Truchet, Laura; Walland, Julia; Wüthrich, Daniel; Boujon, Céline L; Posthaus, Horst; Bruggmann, Rémy; Schüpbach-Regula, Gertraud; Oevermann, Anna; Seuberlich, Torsten

    2017-09-01

    Neuroinfectious diseases in livestock represent a severe threat to animal health, but their prevalence is not well documented and the etiology of disease often remains unidentified. The aims of this study were to generate baseline data on the prevalence of neuroinfectious diseases in cattle in Switzerland by neuropathological survey, and to identify disease-associated pathogens. The survey was performed over a 1-year period using a representative number of brainstem samples (n=1816) from fallen cattle. In total, 4% (n=73) of the animals had significant lesions, the most frequent types of which were indicative of viral (n=27) and bacterial (n=31) etiologies. Follow-up diagnostics by immunohistochemistry, PCR protocols and next-generation sequencing identified infection with Listeria monocytogenes (n=6), ovine herpesvirus 2 (n=7), bovine astrovirus CH13 (n=2), bovine herpesvirus 6 (n=6), bovine retrovirus CH15 (n=2), posavirus 1 (n=2), and porcine astroviruses (n=2). A retrospective questionnaire-based investigation indicated that animals' owners observed clinical signs of neurological disease in about one-third of cases with lesions, which was estimated to correspond to approximately 85 cases per year in the adult fallen cattle population in Switzerland. This estimate stands in sharp contrast to the number of cases reported to the authorities and reveals a gap in disease surveillance. Systematic neuropathological examination and follow-up molecular testing of neurologically diseased cattle could significantly enhance the efficiency of disease detection for the purposes of estimating the prevalence of endemic diseases, identifying new or re-emerging pathogens, and providing "early warnings" of disease outbreaks. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Early behavioral changes and quantitative analysis of neuropathological features in murine prion disease

    Science.gov (United States)

    Borner, Roseane; Bento-Torres, João; Souza, Diego RV; Sadala, Danyelle B; Trevia, Nonata; Farias, José Augusto; Lins, Nara; Passos, Aline; Quintairos, Amanda; Diniz, José Antônio; Perry, Victor Hugh; Vasconcelos, Pedro Fernando; Cunningham, Colm

    2011-01-01

    Behavioral and neuropathological changes have been widely investigated in murine prion disease but stereological based unbiased estimates of key neuropathological features have not been carried out. After injections of ME7 infected (ME7) or normal brain homogenates (NBH) into dorsal CA1 of albino Swiss mice and C57BL6, we assessed behavioral changes on hippocampal-dependent tasks. We also estimated by optical fractionator at 15 and 18 weeks post-injections (w.p.i.) the total number of neurons, reactive astrocytes, activated microglia and perineuronal nets (PN) in the polymorphic layer of dentate gyrus (PolDG), CA1 and septum in albino Swiss mice. On average, early behavioral changes in albino Swiss mice start four weeks later than in C57BL6. Cluster and discriminant analysis of behavioral data in albino Swiss mice revealed that four of nine subjects start to change their behavior at 12 w.p.i. and reach terminal stage at 22 w.p.i and the remaining subjects start at 22 w.p.i. and reach terminal stage at 26 w.p.i. Biotinylated dextran-amine BDA-tracer experiments in mossy fiber pathway confirmed axonal degeneration and stereological data showed that early astrocytosis, microgliosis and reduction in the perineuronal nets are independent of a change in the number of neuronal cell bodies. Statistical analysis revealed that the septal region had greater levels of neuroinflammation and extracellular matrix damage than CA1. This stereological and multivariate analysis at early stages of disease in an outbred model of prion disease provided new insights connecting behavioral changes and neuroinflammation and seems to be important to understand the mechanisms of prion disease progression. PMID:21862877

  20. Development of antipsychotic medications with novel mechanisms of action based on computational modeling of hippocampal neuropathology.

    Directory of Open Access Journals (Sweden)

    Peter J Siekmeier

    Full Text Available A large number of cellular level abnormalities have been identified in the hippocampus of schizophrenic subjects. Nonetheless, it remains uncertain how these pathologies interact at a system level to create clinical symptoms, and this has hindered the development of more effective antipsychotic medications. Using a 72-processor supercomputer, we created a tissue level hippocampal simulation, featuring multicompartmental neuron models with multiple ion channel subtypes and synaptic channels with realistic temporal dynamics. As an index of the schizophrenic phenotype, we used the specific inability of the model to attune to 40 Hz (gamma band stimulation, a well-characterized abnormality in schizophrenia. We examined several possible combinations of putatively schizophrenogenic cellular lesions by systematically varying model parameters representing NMDA channel function, dendritic spine density, and GABA system integrity, conducting 910 trials in total. Two discrete "clusters" of neuropathological changes were identified. The most robust was characterized by co-occurring modest reductions in NMDA system function (-30% and dendritic spine density (-30%. Another set of lesions had greater NMDA hypofunction along with low level GABA system dysregulation. To the schizophrenic model, we applied the effects of 1,500 virtual medications, which were implemented by varying five model parameters, independently, in a graded manner; the effects of known drugs were also applied. The simulation accurately distinguished agents that are known to lack clinical efficacy, and identified novel mechanisms (e.g., decrease in AMPA conductance decay time constant, increase in projection strength of calretinin-positive interneurons and combinations of mechanisms that could re-equilibrate model behavior. These findings shed light on the mechanistic links between schizophrenic neuropathology and the gamma band oscillatory abnormalities observed in the illness. As such, they

  1. Effect of Common Neuropathologies on Progression of Late Life Cognitive Impairment

    Science.gov (United States)

    Yu, Lei; Boyle, Patricia A.; Leurgans, Sue; Schneider, Julie A.; Kryscio, Richard J.; Wilson, Robert S.; Bennett, David A.

    2015-01-01

    Brain pathologies of Alzheimer’s, cerebrovascular and Lewy body diseases are common in old age, but the relationship of these pathologies with progression from normal cognitive function to the various stages of cognitive impairment is unknown. In this study, we fit latent Markov models from longitudinal cognitive data to empirically derive three latent stages corresponding to no impairment, mild impairment, and moderate impairment; then, we examined the associations of common neuropathologies with the rates of transition among these stages. Cognitive and neuropathological data were available from 653 autopsied participants in two ongoing cohort studies of aging who were cognitively healthy at baseline (mean baseline age 79.1 years) and had longitudinal cognitive data. On average, participants in these analyses developed mild impairment 5 years after enrollment, progressed to moderate impairment after an additional 3.4 years, and stayed impaired for 2.8 years until death. AD and chronic macroscopic infarcts were associated with a higher risk of progression to mild impairment and subsequently to moderate impairment. By contrast, Lewy bodies were associated only with progression from mild to moderate impairment. The 5-year probability of progression to mild or moderate impairment was 20% for persons without any of these three pathologies, 38% for AD only, 51% for AD and macroscopic infarcts, and 56% for AD, infarcts and Lewy bodies. Thus, the presence of AD pathology alone nearly doubles the risk of developing cognitive impairment in late life, and the presence of multiple pathologies further increases this risk over multiple years prior to death. PMID:25976345

  2. Mutant alpha-synuclein causes age-dependent neuropathology in monkey brain.

    Science.gov (United States)

    Yang, Weili; Wang, Guohao; Wang, Chuan-En; Guo, Xiangyu; Yin, Peng; Gao, Jinquan; Tu, Zhuchi; Wang, Zhengbo; Wu, Jing; Hu, Xintian; Li, Shihua; Li, Xiao-Jiang

    2015-05-27

    Parkinson's disease (PD) is an age-dependent neurodegenerative disease that often occurs in those over age 60. Although rodents and small animals have been used widely to model PD and investigate its pathology, their short life span makes it difficult to assess the aging-related pathology that is likely to occur in PD patient brains. Here, we used brain tissues from rhesus monkeys at 2-3, 7-8, and >15 years of age to examine the expression of Parkin, PINK1, and α-synuclein, which are known to cause PD via loss- or gain-of-function mechanisms. We found that α-synuclein is increased in the older monkey brains, whereas Parkin and PINK1 are decreased or remain unchanged. Because of the gain of toxicity of α-synuclein, we performed stereotaxic injection of lentiviral vectors expressing mutant α-synuclein (A53T) into the substantia nigra of monkeys and found that aging also increases the accumulation of A53T in neurites and its associated neuropathology. A53T also causes more extensive reactive astrocytes and axonal degeneration in monkey brain than in mouse brain. Using monkey brain tissues, we found that A53T interacts with neurofascin, an adhesion molecule involved in axon subcellular targeting and neurite outgrowth. Aged monkey brain tissues show an increased interaction of neurofascin with A53T. Overexpression of A53T causes neuritic toxicity in cultured neuronal cells, which can be attenuated by transfected neurofascin. These findings from nonhuman primate brains reveal age-dependent pathological and molecular changes that could contribute to the age-dependent neuropathology in PD. Copyright © 2015 the authors 0270-6474/15/358345-14$15.00/0.

  3. Similarity Measure of Graphs

    Directory of Open Access Journals (Sweden)

    Amine Labriji

    2017-07-01

    Full Text Available The topic of identifying the similarity of graphs was considered as highly recommended research field in the Web semantic, artificial intelligence, the shape recognition and information research. One of the fundamental problems of graph databases is finding similar graphs to a graph query. Existing approaches dealing with this problem are usually based on the nodes and arcs of the two graphs, regardless of parental semantic links. For instance, a common connection is not identified as being part of the similarity of two graphs in cases like two graphs without common concepts, the measure of similarity based on the union of two graphs, or the one based on the notion of maximum common sub-graph (SCM, or the distance of edition of graphs. This leads to an inadequate situation in the context of information research. To overcome this problem, we suggest a new measure of similarity between graphs, based on the similarity measure of Wu and Palmer. We have shown that this new measure satisfies the properties of a measure of similarities and we applied this new measure on examples. The results show that our measure provides a run time with a gain of time compared to existing approaches. In addition, we compared the relevance of the similarity values obtained, it appears that this new graphs measure is advantageous and  offers a contribution to solving the problem mentioned above.

  4. Processes of Similarity Judgment

    Science.gov (United States)

    Larkey, Levi B.; Markman, Arthur B.

    2005-01-01

    Similarity underlies fundamental cognitive capabilities such as memory, categorization, decision making, problem solving, and reasoning. Although recent approaches to similarity appreciate the structure of mental representations, they differ in the processes posited to operate over these representations. We present an experiment that…

  5. Judgments of brand similarity

    NARCIS (Netherlands)

    Bijmolt, THA; Wedel, M; Pieters, RGM; DeSarbo, WS

    This paper provides empirical insight into the way consumers make pairwise similarity judgments between brands, and how familiarity with the brands, serial position of the pair in a sequence, and the presentation format affect these judgments. Within the similarity judgment process both the

  6. A Mutual Self- and Informant-Report of Cognitive Complaint Correlates with Neuropathological Outcomes in Mild Cognitive Impairment.

    Directory of Open Access Journals (Sweden)

    Katherine A Gifford

    Full Text Available This study examines whether different sources of cognitive complaint (i.e., self and informant predict Alzheimer's disease (AD neuropathology in elders with mild cognitive impairment (MCI.Data were drawn from the National Alzheimer's Coordinating Center Uniform and Neuropathology Datasets (observational studies for participants with a clinical diagnosis of MCI and postmortem examination (n = 1843, 74±8 years, 52% female. Cognitive complaint (0.9±0.5 years prior to autopsy was classified into four mutually exclusive groups: no complaint, self-only, informant-only, or mutual (both self and informant complaint. Postmortem neuropathological outcomes included amyloid plaques and neurofibrillary tangles. Proportional odds regression related complaint to neuropathology, adjusting for age, sex, race, education, depressed mood, cognition, APOE4 status, and last clinical visit to death interval.Mutual complaint related to increased likelihood of meeting NIA/Reagan Institute (OR = 6.58, p = 0.004 and Consortium to Establish a Registry for Alzheimer's Disease criteria (OR = 5.82, p = 0.03, and increased neurofibrillary tangles (OR = 3.70, p = 0.03, neuritic plaques (OR = 3.52, p = 0.03, and diffuse plaques (OR = 4.35, p = 0.02. Informant-only and self-only complaint was not associated with any neuropathological outcome (all p-values>0.12.In MCI, mutual cognitive complaint relates to AD pathology whereas self-only or informant-only complaint shows no relation to pathology. Findings support cognitive complaint as a marker of unhealthy brain aging and highlight the importance of obtaining informant corroboration to increase confidence of underlying pathological processes.

  7. Neuropathological Comparison of Adult Onset and Juvenile Huntington's Disease with Cerebellar Atrophy: A Report of a Father and Son.

    Science.gov (United States)

    Latimer, Caitlin S; Flanagan, Margaret E; Cimino, Patrick J; Jayadev, Suman; Davis, Marie; Hoffer, Zachary S; Montine, Thomas J; Gonzalez-Cuyar, Luis F; Bird, Thomas D; Keene, C Dirk

    2017-01-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a trinucleotide (CAG) repeat expansion in huntingtin (HTT) on chromosome 4. Anticipation can cause longer repeat expansions in children of HD patients. Juvenile Huntington's disease (JHD), defined as HD arising before age 20, accounts for 5-10% of HD cases, with cases arising in the first decade accounting for approximately 1%. Clinically, JHD differs from the predominately choreiform adult onset Huntington's disease (AOHD) with variable presentations, including symptoms such as myoclonus, seizures, Parkinsonism, and cognitive decline. The neuropathologic changes of AOHD are well characterized, but there are fewer reports that describe the neuropathology of JHD. Here we report a case of a six-year-old boy with paternally-inherited JHD caused by 169 CAG trinucleotide repeats who presented at age four with developmental delay, dysarthria, and seizures before dying at age 6. The boy's clinical presentation and neuropathological findings are directly compared to those of his father, who presented with AOHD and 54 repeats. A full autopsy was performed for the JHD case and a brain-only autopsy was performed for the AOHD case. Histochemically- and immunohistochemically-stained slides were prepared from formalin-fixed, paraffin-embedded tissue sections. Both cases had neuropathology corresponding to Vonsattel grade 3. The boy also had cerebellar atrophy with huntingtin-positive inclusions in the cerebellum, findings not present in the father. Autopsies of father and son provide a unique opportunity to compare and contrast the neuropathologic findings of juvenile and adult onset HD while also providing the first immunohistochemical evidence of cerebellar involvement in JHD. Additionally this is the first known report to include findings from peripheral tissue in a case of JHD.

  8. Gender similarities and differences.

    Science.gov (United States)

    Hyde, Janet Shibley

    2014-01-01

    Whether men and women are fundamentally different or similar has been debated for more than a century. This review summarizes major theories designed to explain gender differences: evolutionary theories, cognitive social learning theory, sociocultural theory, and expectancy-value theory. The gender similarities hypothesis raises the possibility of theorizing gender similarities. Statistical methods for the analysis of gender differences and similarities are reviewed, including effect sizes, meta-analysis, taxometric analysis, and equivalence testing. Then, relying mainly on evidence from meta-analyses, gender differences are reviewed in cognitive performance (e.g., math performance), personality and social behaviors (e.g., temperament, emotions, aggression, and leadership), and psychological well-being. The evidence on gender differences in variance is summarized. The final sections explore applications of intersectionality and directions for future research.

  9. Linear pharmacokinetic parameters for monoclonal antibodies are similar within a species and across different pharmacological targets: A comparison between human, cynomolgus monkey and hFcRn Tg32 transgenic mouse using a population-modeling approach.

    Science.gov (United States)

    Betts, Alison; Keunecke, Anne; van Steeg, Tamara J; van der Graaf, Piet H; Avery, Lindsay B; Jones, Hannah; Berkhout, Jan

    2018-04-10

    The linear pharmacokinetics (PK) of therapeutic monoclonal antibodies (mAbs) can be considered a class property with values that are similar to endogenous IgG. Knowledge of these parameters across species could be used to avoid unnecessary in vivo PK studies and to enable early PK predictions and pharmacokinetic/pharmacodynamic (PK/PD) simulations. In this work, population-pharmacokinetic (popPK) modeling was used to determine a single set of 'typical' popPK parameters describing the linear PK of mAbs in human, cynomolgus monkey and transgenic mice expressing the human neonatal Fc receptor (hFcRn Tg32), using a rich dataset of 27 mAbs. Non-linear PK was excluded from the datasets and a 2-compartment model was applied to describe mAb disposition. Typical human popPK estimates compared well with data from comparator mAbs with linear PK in the clinic. Outliers with higher than typical clearance were found to have non-specific interactions in an affinity-capture self-interaction nanoparticle spectroscopy assay, offering a potential tool to screen out these mAbs at an early stage. Translational strategies were investigated for prediction of human linear PK of mAbs, including use of typical human popPK parameters and allometric exponents from cynomolgus monkey and Tg32 mouse. Each method gave good prediction of human PK with parameters predicted within 2-fold. These strategies offer alternative options to the use of cynomolgus monkeys for human PK predictions of linear mAbs, based on in silico methods (typical human popPK parameters) or using a rodent species (Tg32 mouse), and call into question the value of completing extensive in vivo preclinical PK to inform linear mAb PK.

  10. Similarity or difference?

    DEFF Research Database (Denmark)

    Villadsen, Anders Ryom

    2013-01-01

    While the organizational structures and strategies of public organizations have attracted substantial research attention among public management scholars, little research has explored how these organizational core dimensions are interconnected and influenced by pressures for similarity....... In this paper I address this topic by exploring the relation between expenditure strategy isomorphism and structure isomorphism in Danish municipalities. Different literatures suggest that organizations exist in concurrent pressures for being similar to and different from other organizations in their field......-shaped relation exists between expenditure strategy isomorphism and structure isomorphism in a longitudinal quantitative study of Danish municipalities....

  11. Neuropathological findings processed by artificial neural networks (ANNs can perfectly distinguish Alzheimer's patients from controls in the Nun Study

    Directory of Open Access Journals (Sweden)

    Snowdon David

    2007-06-01

    Full Text Available Abstract Background Many reports have described that there are fewer differences in AD brain neuropathologic lesions between AD patients and control subjects aged 80 years and older, as compared with the considerable differences between younger persons with AD and controls. In fact some investigators have suggested that since neurofibrillary tangles (NFT can be identified in the brains of non-demented elderly subjects they should be considered as a consequence of the aging process. At present, there are no universally accepted neuropathological criteria which can mathematically differentiate AD from healthy brain in the oldest old. The aim of this study is to discover the hidden and non-linear associations among AD pathognomonic brain lesions and the clinical diagnosis of AD in participants in the Nun Study through Artificial Neural Networks (ANNs analysis Methods The analyses were based on 26 clinically- and pathologically-confirmed AD cases and 36 controls who had normal cognitive function. The inputs used for the analyses were just NFT and neuritic plaques counts in neocortex and hippocampus, for which, despite substantial differences in mean lesions counts between AD cases and controls, there was a substantial overlap in the range of lesion counts. Results By taking into account the above four neuropathological features, the overall predictive capability of ANNs in sorting out AD cases from normal controls reached 100%. The corresponding accuracy obtained with Linear Discriminant Analysis was 92.30%. These results were consistently obtained in ten independent experiments. The same experiments were carried out with ANNs on a subgroup of 13 non severe AD patients and on the same 36 controls. The results obtained in terms of prediction accuracy with ANNs were exactly the same. Input relevance analysis confirmed the relative dominance of NFT in neocortex in discriminating between AD patients and controls and indicated the lesser importance

  12. Neuropathological findings processed by artificial neural networks (ANNs) can perfectly distinguish Alzheimer's patients from controls in the Nun Study.

    Science.gov (United States)

    Grossi, Enzo; Buscema, Massimo P; Snowdon, David; Antuono, Piero

    2007-06-21

    Many reports have described that there are fewer differences in AD brain neuropathologic lesions between AD patients and control subjects aged 80 years and older, as compared with the considerable differences between younger persons with AD and controls. In fact some investigators have suggested that since neurofibrillary tangles (NFT) can be identified in the brains of non-demented elderly subjects they should be considered as a consequence of the aging process. At present, there are no universally accepted neuropathological criteria which can mathematically differentiate AD from healthy brain in the oldest old. The aim of this study is to discover the hidden and non-linear associations among AD pathognomonic brain lesions and the clinical diagnosis of AD in participants in the Nun Study through Artificial Neural Networks (ANNs) analysis The analyses were based on 26 clinically- and pathologically-confirmed AD cases and 36 controls who had normal cognitive function. The inputs used for the analyses were just NFT and neuritic plaques counts in neocortex and hippocampus, for which, despite substantial differences in mean lesions counts between AD cases and controls, there was a substantial overlap in the range of lesion counts. By taking into account the above four neuropathological features, the overall predictive capability of ANNs in sorting out AD cases from normal controls reached 100%. The corresponding accuracy obtained with Linear Discriminant Analysis was 92.30%. These results were consistently obtained in ten independent experiments. The same experiments were carried out with ANNs on a subgroup of 13 non severe AD patients and on the same 36 controls. The results obtained in terms of prediction accuracy with ANNs were exactly the same. Input relevance analysis confirmed the relative dominance of NFT in neocortex in discriminating between AD patients and controls and indicated the lesser importance played by NP in the hippocampus. The results of this study

  13. Humans and insects decide in similar ways

    NARCIS (Netherlands)

    Louâpre, P.; van Alphen, J.J.M.; Pierre, J.S.

    2010-01-01

    Behavioral ecologists assume that animals use a motivational mechanism for decisions such as action selection and time allocation, allowing the maximization of their fitness. They consider both the proximate and ultimate causes of behavior in order to understand this type of decision-making in

  14. Comparing Harmonic Similarity Measures

    NARCIS (Netherlands)

    de Haas, W.B.; Robine, M.; Hanna, P.; Veltkamp, R.C.; Wiering, F.

    2010-01-01

    We present an overview of the most recent developments in polyphonic music retrieval and an experiment in which we compare two harmonic similarity measures. In contrast to earlier work, in this paper we specifically focus on the symbolic chord description as the primary musical representation and

  15. Hemodynamic and neuropathological analysis in rats with aluminum trichloride-induced Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Szu-Ming Chen

    Full Text Available BACKGROUND AND AIMS: Hemodynamic normality is crucial to maintaining the integrity of cerebral vessels and, therefore, preserving the cognitive functions of Alzheimer's disease patients. This study investigates the implications of the hemodynamic changes and the neuropathological diversifications of AlCl3-induced AD. METHODS: The experimental animals were 8- to 12-wk-old male Wistar rats. The rats were randomly divided into 2 groups: a control group and a (+control group. Food intake, water intake, and weight changes were recorded daily for 22 wk. Synchronously, the regional cerebral blood flow (rCBF of the rats with AlCl3-induced AD were measured using magnetic resonance imaging (MRI. The hemorheological parameters were analyzed using a computerized auto-rotational rheometer. The brain tissue of the subjects was analyzed using immunohistological chemical (IHC staining to determine the beta-amyloid (Aβ levels. RESULTS: The results of hemodynamic analysis revealed that the whole blood viscosity (WBV, fibrinogen, plasma viscosity and RBC aggregation index (RAI in (+control were significantly higher than that of control group, while erythrocyte electrophoresis (EI of whole blood in (+control were significantly lower than that of control group. The results of acetylcholinesterase-RBC (AChE-RBCin the (+control group was significantly higher than that of the control group. The results also show that the reduction of rCBF in rats with AlCl3-induced AD was approximately 50% to 60% that of normal rats. IHC stain results show that significantly more Aβ plaques accumulated in the hippocampus and cortex of the (+control than in the control group. CONCLUSION: The results accentuate the importance of hemorheology and reinforce the specific association between hemodynamic and neuropathological changes in rats with AlCl3-induced AD. Hemorheological parameters, such as WBV and fibrinogen, and AChE-RBC were ultimately proven to be useful biomarkers of the

  16. "Boomerang Neuropathology" of Late-Onset Alzheimer's Disease is Shrouded in Harmful "BDDS": Breathing, Diet, Drinking, and Sleep During Aging.

    Science.gov (United States)

    Daulatzai, Mak Adam

    2015-07-01

    Brain damage begins years before substantial neurodegeneration and Alzheimer's dementia. Crucial fundamental activities of life are breathing, eating, drinking, and sleeping. When these pivotal functions are maligned over a prolonged period, they impart escalating dyshomeostasis. The latter may lead to disastrous consequences including cognitive dysfunction and Alzheimer's disease (AD). The current theme here is that multiple pathophysiological derangements are promoted over a prolonged period by the very fundamental activities of life-when "rendered unhealthy." They may converge on several regulating/modulating factors (e.g., mitochondrial energy production, oxidative stress, innate immunity, and vascular function) and promote insidious neuropathology that culminates in cognitive decline in the aged. This is of course associated with the accumulation of amyloid beta and phosphorylated tau in the brain. Epidemiological, biomarker, and neuroimaging studies have provided significant copious evidence on the presence of indolent prodromal AD neuropathology many years prior to symptomatic onset. Progressive oxidative damage to specific gene promoters may result in gene silencing. A mechanistic link may possibly exist between epigenomic state, DNA damage, and chronically unhealthy/dysfunctional body systems. This paper, therefore, addresses and delineates the deleterious pathophysiological impact triggered by dysfunctional breathing, harmful diet, excess of alcohol consumption, and sleep deprivation; indeed, their impact may alter epigenetic state. It is mandatory, therefore, to abrogate cognitive decline and attenuate AD pathology through adoption of a healthy lifestyle, in conjunction with combination therapy with known moderators of cognitive decline. This strategy may thwart multiple concurrent and synergistic pathologies, including epigenetic dysfunction. A multi-factorial therapeutic intervention is required to overcome wide ranging neuropathology and multi

  17. Slower EEG alpha generation, synchronization and “flow”—possible biomarkers of cognitive impairment and neuropathology of minor stroke

    OpenAIRE

    Petrovic, Jelena; Milosevic, Vuk; Zivkovic, Miroslava; Stojanov, Dragan; Milojkovic, Olga; Kalauzi, Aleksandar; Saponjic, Jasna

    2017-01-01

    Background We investigated EEG rhythms, particularly alpha activity, and their relationship to post-stroke neuropathology and cognitive functions in the subacute and chronic stages of minor strokes. Methods We included 10 patients with right middle cerebral artery (MCA) ischemic strokes and 11 healthy controls. All the assessments of stroke patients were done both in the subacute and chronic stages. Neurological impairment was measured using the National Institute of Health Stroke Scale (NIHS...

  18. Stimulation of Central A1 Adenosine Receptors Suppresses Seizure and Neuropathology in a Soman Nerve Agent Seizure Rat Model

    Science.gov (United States)

    2014-05-22

    implantation site, Nissl stained , and then analyzed by a trained pathologist to verify the accuracy of cannulae placement and evaluate toxicity. The second...transcardial perfusion and fixation, the brains were sectioned and stained with Nissl . A trained pathologist then analyzed the sections and verified that CPA...proto- col was used for assessing neuropathology in the subsequent soman seizure experiments. Those brains were serial sec- tioned at 5 mm, stained

  19. Long-term human immune system reconstitution in non-obese diabetic (NOD)-Rag (-)-γ chain (-) (NRG) mice is similar but not identical to the original stem cell donor.

    Science.gov (United States)

    Harris, D T; Badowski, M; Balamurugan, A; Yang, O O

    2013-12-01

    The murine immune system is not necessarily identical to it human counterpart, which has led to the construction of humanized mice. The current study analysed whether or not a human immune system contained within the non-obese diabetic (NOD)-Rag1(null) -γ chain(null) (NRG) mouse model was an accurate representation of the original stem cell donor and if multiple mice constructed from the same donor were similar to one another. To that end, lightly irradiated NRG mice were injected intrahepatically on day 1 of life with purified cord blood-derived CD34(+) stem and progenitor cells. Multiple mice were constructed from each cord blood donor. Mice were analysed quarterly for changes in the immune system, and followed for periods up to 12 months post-transplant. Mice from the same donor were compared directly with each other as well as with the original donor. Analyses were performed for immune reconstitution, including flow cytometry, T cell receptor (TCR) and B cell receptor (BCR) spectratyping. It was observed that NRG mice could be 'humanized' long-term using cord blood stem cells, and that animals constructed from the same cord blood donor were nearly identical to one another, but quite different from the original stem cell donor immune system. © 2013 British Society for Immunology.

  20. Tau, APP, NCT and BACE1 in lymphocytes through cognitively normal ageing and neuropathology

    Directory of Open Access Journals (Sweden)

    MARISOL HERRERA-RIVERO

    2013-01-01

    Full Text Available Although Alzheimer's disease is a brain disorder, a number of peripheral alterations have been found in these patients; however, little is known about how the key genes involved in the pathophysiology express in peripheral cells such as lymphocytes during normal compared to neuropathological ageing. We analysed the expression of tau, of the amyloid precursor protein, of nicastrin and of the β-site APP cleaving enzyme genes by RT-PCR in lymphocytes from a small group of late-onset Alzheimer's disease patients, from aged patients suffering from neuropsychological conditions different from Alzheimer's and from cognitively healthy subjects divided in four groups by age. We also investigated correlations between gene expression and levels of blood pressure, glucose, total cholesterol and triglycerides as risk factors for Alzheimer's. Results show no tau expression in lymphocytes, a lack of detection of nicastrin expression in Alzheimer's patients and correlations between the medical conditions studied and gene expression in lymphocytes. We believe nicastrin gene expression in lymphocytes should be considered of interest for further analyses in a wider population to investigate whether it might represent a potential biomarker to differentiate Alzheimer's from other neuropsychological disorders.

  1. A Single Neonatal Exposure to BMAA in a Rat Model Produces Neuropathology Consistent with Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Laura Louise Scott

    2017-12-01

    Full Text Available Although cyanobacterial β-N-methylamino-l-alanine (BMAA has been implicated in the development of Alzheimer’s Disease (AD, Parkinson’s Disease (PD and Amyotrophic Lateral Sclerosis (ALS, no BMAA animal model has reproduced all the neuropathology typically associated with these neurodegenerative diseases. We present here a neonatal BMAA model that causes β-amyloid deposition, neurofibrillary tangles of hyper-phosphorylated tau, TDP-43 inclusions, Lewy bodies, microbleeds and microgliosis as well as severe neuronal loss in the hippocampus, striatum, substantia nigra pars compacta, and ventral horn of the spinal cord in rats following a single BMAA exposure. We also report here that BMAA exposure on particularly PND3, but also PND4 and 5, the critical period of neurogenesis in the rodent brain, is substantially more toxic than exposure to BMAA on G14, PND6, 7 and 10 which suggests that BMAA could potentially interfere with neonatal neurogenesis in rats. The observed selective toxicity of BMAA during neurogenesis and, in particular, the observed pattern of neuronal loss observed in BMAA-exposed rats suggest that BMAA elicits its effect by altering dopamine and/or serotonin signaling in rats.

  2. Heterogeneity in Red Wine Polyphenolic Contents Differentially Influences Alzheimer's Disease-type Neuropathology and Cognitive Deterioration

    Science.gov (United States)

    Ho, Lap; Chen, Ling Hong; Wang, Jun; Zhao, Wei; Talcott, Stephen T.; Ono, Kenjiro; Teplow, David; Humala, Nelson; Cheng, Alice; Percival, Susan S.; Ferruzzi, Mario; Janle, Elsa; Dickstein, Dara L.; Pasinetti, Giulio Maria

    2009-01-01

    We recently found that moderate consumption of two unrelated red wines generate from different grape species, a Cabernet Sauvignon and a muscadine wine that are characterized by distinct component composition of polyphenolic compounds, significantly attenuated the development of Alzheimer's disease (AD)-type brain pathology and memory deterioration in a transgenic AD mouse model. Interestingly, our evidence suggests that the two red wines attenuated AD phenotypes through independent mechanisms. In particular, we previously found that treatment with Cabernet Sauvignon reduced the generation of AD-type amyloid-β (Aβ) peptides. In contrast, evidence from our present study suggests that muscadine treatment attenuates Aβ neuropathology and Aβ-related cognitive deterioration in Tg2576 mice by interfering with the oligomerization of Aβ molecules to soluble high-molecular-weight Aβ oligomer species that are responsible for initiating a cascade of cellular events resulting in cognitive decline. Collectively, our observations suggest that distinct polyphenolic compounds from red wines may be bioavailable at the organism level and beneficially modulate AD phenotypes through multiple Aβ-related mechanisms. Results from these studies suggest the possibility of developing a “combination” of dietary polyphenolic compounds for AD prevention and/or therapy by modulating multiple Aβ-related mechanisms. PMID:19158422

  3. Anterior temporal white matter lesions in myotonic dystrophy with intellectual impairment: an MRI and neuropathological study

    International Nuclear Information System (INIS)

    Ogata, A.; Tashiro, K.; Terae, S.; Fujita, M.

    1998-01-01

    We studied 12 patients with myotonic dystrophy using MRI and the Mini-mental state examination (MMSE), to see it specific MRI findings were associated with intellectual impairment. We also compared them with the neuropathological findings in an autopsy case of MD with intellectual impairment. Mild intellectual impairment was found in 8 of the 12 patients. On T 2-weighted and proton density-weighted images, high-intensity areas were seen in cerebral white matter in 10 of the 12 patients. In seven of these, anterior temporal white-matter lesions (ATWML) were found; all seven had mild intellectual impairment (MMSE 22-26), whereas none of the four patients with normal mentation had ATWML. In only one of the eight patients with intellectual impairment were white-matter lesions not found. Pathological findings were severe loss and disordered arrangement of myelin sheaths and axons in addition to heterotopic neurons within anterior temporal white matter. Bilateral ATWML might be a factor for intellectual impairment in MD. The retrospective pathological study raised the possibility that the ATWML are compatible with focal dysplasia of white matter. (orig.)

  4. Correlation between social proximity and mobility similarity.

    Science.gov (United States)

    Fan, Chao; Liu, Yiding; Huang, Junming; Rong, Zhihai; Zhou, Tao

    2017-09-20

    Human behaviors exhibit ubiquitous correlations in many aspects, such as individual and collective levels, temporal and spatial dimensions, content, social and geographical layers. With rich Internet data of online behaviors becoming available, it attracts academic interests to explore human mobility similarity from the perspective of social network proximity. Existent analysis shows a strong correlation between online social proximity and offline mobility similarity, namely, mobile records between friends are significantly more similar than between strangers, and those between friends with common neighbors are even more similar. We argue the importance of the number and diversity of common friends, with a counter intuitive finding that the number of common friends has no positive impact on mobility similarity while the diversity plays a key role, disagreeing with previous studies. Our analysis provides a novel view for better understanding the coupling between human online and offline behaviors, and will help model and predict human behaviors based on social proximity.

  5. IgG and complement deposition and neuronal loss in cats and humans with epilepsy and voltage-gated potassium channel complex antibodies.

    Science.gov (United States)

    Klang, Andrea; Schmidt, Peter; Kneissl, Sibylle; Bagó, Zoltán; Vincent, Angela; Lang, Bethan; Moloney, Teresa; Bien, Christian G; Halász, Péter; Bauer, Jan; Pákozdy, Akos

    2014-05-01

    Voltage-gated potassium channel complex (VGKC-complex) antibody (Ab) encephalitis is a well-recognized form of limbic encephalitis in humans, usually occurring in the absence of an underlying tumor. The patients have a subacute onset of seizures, magnetic resonance imaging findings suggestive of hippocampal inflammation, and high serum titers of Abs against proteins of the VGKC-complex, particularly leucine-rich, glioma-inactivated 1 (LGI1). Most patients are diagnosed promptly and recover substantially with immunotherapies; consequently, neuropathological data are limited. We have recently shown that feline complex partial cluster seizures with orofacial involvement (FEPSO) in cats can also be associated with Abs against VGKC-complexes/LGI1. Here we examined the brains of cats with FEPSO and compared the neuropathological findings with those in a human with VGKC-complex-Ab limbic encephalitis. Similar to humans, cats with VGKC-complex-Ab and FEPSO have hippocampal lesions with only moderate T-cell infiltrates but with marked IgG infiltration and complement C9neo deposition on hippocampal neurons, associated with neuronal loss. These findings provide further evidence that FEPSO is a feline form of VGKC-complex-Ab limbic encephalitis and provide a model for increasing understanding of the human disease.

  6. Similarities and differences between the responses induced in human phagocytes through activation of the medium chain fatty acid receptor GPR84 and the short chain fatty acid receptor FFA2R.

    Science.gov (United States)

    Sundqvist, Martina; Christenson, Karin; Holdfeldt, André; Gabl, Michael; Mårtensson, Jonas; Björkman, Lena; Dieckmann, Regis; Dahlgren, Claes; Forsman, Huamei

    2018-05-01

    GPR84 is a recently de-orphanized member of the G-protein coupled receptor (GPCR) family recognizing medium chain fatty acids, and has been suggested to play important roles in inflammation. Due to the lack of potent and selective GPR84 ligands, the basic knowledge related to GPR84 functions is very limited. In this study, we have characterized the GPR84 activation profile and regulation mechanism in human phagocytes, using two recently developed small molecules that specifically target GPR84 agonistically (ZQ16) and antagonistically (GLPG1205), respectively. Compared to our earlier characterization of the short chain fatty acid receptor FFA2R which is functionally expressed in neutrophils but not in monocytes, GPR84 is expressed in both cell types and in monocyte-derived macrophages. In neutrophils, the GPR84 agonist had an activation profile very similar to that of FFA2R. The GPR84-mediated superoxide release was low in naïve cells, but the response could be significantly primed by TNFα and by the actin cytoskeleton disrupting agent Latrunculin A. Similar to that of FFA2R, a desensitization mechanism bypassing the actin cytoskeleton was utilized by GPR84. All ZQ16-mediated cellular responses were sensitive to GLPG1205, confirming the GPR84-dependency. Finally, our data of in vivo transmigrated tissue neutrophils indicate that both GPR84 and FFA2R are involved in neutrophil recruitment processes in vivo. In summary, we show functional similarities but also some important differences between GPR84 and FFA2R in human phagocytes, thus providing some mechanistic insights into GPR84 regulation in blood neutrophils and cells recruited to an aseptic inflammatory site in vivo. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Human Treponema pallidum 11q/j isolate belongs to subsp. endemicum but contains two loci with a sequence in TP0548 and TP0488 similar to subsp. pertenue and subsp. pallidum, respectively.

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    Lenka Mikalová

    2017-03-01

    Full Text Available Treponema pallidum subsp. endemicum (TEN is the causative agent of endemic syphilis (bejel. An unusual human TEN 11q/j isolate was obtained from a syphilis-like primary genital lesion from a patient that returned to France from Pakistan.The TEN 11q/j isolate was characterized using nested PCR followed by Sanger sequencing and/or direct Illumina sequencing. Altogether, 44 chromosomal regions were analyzed. Overall, the 11q/j isolate clustered with TEN strains Bosnia A and Iraq B as expected from previous TEN classification of the 11q/j isolate. However, the 11q/j sequence in a 505 bp-long region at the TP0488 locus was similar to Treponema pallidum subsp. pallidum (TPA strains, but not to TEN Bosnia A and Iraq B sequences, suggesting a recombination event at this locus. Similarly, the 11q/j sequence in a 613 bp-long region at the TP0548 locus was similar to Treponema pallidum subsp. pertenue (TPE strains, but not to TEN sequences.A detailed analysis of two recombinant loci found in the 11q/j clinical isolate revealed that the recombination event occurred just once, in the TP0488, with the donor sequence originating from a TPA strain. Since TEN Bosnia A and Iraq B were found to contain TPA-like sequences at the TP0548 locus, the recombination at TP0548 took place in a treponeme that was an ancestor to both TEN Bosnia A and Iraq B. The sequence of 11q/j isolate in TP0548 represents an ancestral TEN sequence that is similar to yaws-causing treponemes. In addition to the importance of the 11q/j isolate for reconstruction of the TEN phylogeny, this case emphasizes the possible role of TEN strains in development of syphilis-like lesions.

  8. HOW TO DIFFERENTIATE FRONTOTEMPORAL FROMALZHEIMER’S DEMENTIA? RECENT DEVELOPMENTS INMOLECULAR GENETICS AND NEUROPATHOLOGY

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    Rajko Liščić

    2008-05-01

    Full Text Available Frontotemporal dementia is a major cause of non-Alzheimer dementia (AD. Frontotemporal lobar degeneration (FTLD is used here as an umbrella term for both clinical andneuropathological entities starting before age of 65 years. FTLD differs clinically from ADbecause memory loss is rarely an early symptom. Instead, the dementia of FTLD is usuallydenoted by behavioral and language difficulties, although clinical and cognitive featuresof FTLD may overlap with AD. Aphasia may be prominent, either fluent or nonfluent.Clinical FTLD is associated with a variety of different neuropathological entities, whichshare common feature of preferential degeneration of the frontal and temporal lobes. Whereas, in the past, most attention focused on FTLD pathology associated with tau-positive inclusions and microtubule associated protein tau gene (MAPT mutations (tauopathies,there has recently been greater attention paid to non-tau, ubiquitin positive inclusions(FTLD-U or non-tauopathies. It is now recognized that FTLD-U is the most common pathology associated with clinical FTLD. Clinically, cases with FTLD-U may additionally presentwith or without motor neuron disease and parkinsonism. Majority of familial cases ofFTLD-U have mutations in the progranulin (PRGN gene. Some families of FTLD-U withPGRN mutation (hereditary dysphasic disinhibition dementia 1 and 2 are characterized,besides behavior and language difficulties, by additional memory loss and AD-type pathology. Recently, the ubiquitinated pathological protein in FTLD-U has been identified asTAR DNA binding protein (TDP 43 and found in an increasing number of neurodegenerative diseases, including AD. The overlap between FTLD-U and AD is important since asmany as 20 % of AD cases show some FTLD-U type TDP-43 pathology. Recent developmentshave helped to clarify the relationship between different types of FTLD and related conditions. Understanding and differentiating between FTLD and AD is very important for

  9. Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats.

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    Yuen-Shan Ho

    Full Text Available Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD. To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP processing by increasing the production of sAPPβ and accumulation of β-amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia.

  10. A comparative study of computerized tomograms and neuropathological findings in cerebrovascular diseases

    International Nuclear Information System (INIS)

    Tohgi, Hideo; Mochizuki, Hiroshi; Yamanouchi, Hiroshi; Iio, Masahiro; Yamada, Hideo

    1979-01-01

    The reliability of computed tomography (CT) in the diagnosis of cerebrovascular diseases was studied by comparing CT images and neuropathological findings in 38 autopsied cases. Our special concern was directed toward several factors which caused false positive and false negative results in CT: the size and location of lesions, and the interval between the onset of the disease and the time of CT studies. Infarctions smaller than 5 mm should be interpreted as such with great care, because only 32.1% of them could be detected in CT, and 81.0% of small low density areas supposed to be small infarctions in CT films proved to be false positive in postmortem examination. 41.9% of middle-sized infarctions were detected in CT and 40.9% of middle-sized low density areas were false positive. Most of false positive low density areas appeared on the surface of the cerebrum where deep sulci join, or in the white matter anterior to the anterior horn or posterior to the posterior horn of the lateral ventricles. The possibility of false positive findings became far less, when the number of slices showing low density areas increased. All of the large infarctions were detected in CT. However, immediately after stroke they did not stand out as low density areas. In such cases, the decrease of cerebral sulci due to brain edema and signs of compression in the ventricular system could be the clues to make the diagnosis of large infarctions. The diagnosis of hemorrhagic infarctions was often difficult. Cerebral bleeding could be diagnosed easily by CT in its early period. However, old hematomas which rapidly resolved and became shrunken, could hardly be identified in CT. (author)

  11. Dementia in SPG4 hereditary spastic paraplegia: clinical, genetic, and neuropathologic evidence.

    LENUS (Irish Health Repository)

    Murphy, S

    2012-02-01

    BACKGROUND: Cognitive impairment and dementia has been reported in autosomal dominant hereditary spastic paraparesis (HSP) linked to the SPG4 locus. There has only been one postmortem examination described; not all accept that progressive cognitive decline is a feature of this disorder. OBJECTIVE: A family with SPG4-HSP known to have a deletion of exon 17 in the spastin gene (SPG4delEx17) was cognitively assessed over a 7-year period. The index family member died and a postmortem examination was performed. METHODS: Thirteen family members older than 40 years were clinically and cognitively assessed using the Cambridge Cognitive Assessment over a 7-year period. The presence of SPG4delEx17 was assessed; a neuropathologic examination of the brain of the index family member was performed. RESULTS: Cognitive decline occurred in 6 of the 13 family members and in all 4 older than 60 years. Two genetic deletions were identified: SPG4delEx17 in 12 of the 13 family members and a deletion of SPG6 (SPG6del) in 5. Eight individuals had the SPG4delEx17 deletion only; 4 had evidence of progressive cognitive impairment. Four family members had both SPG4delEx17 and SPG6del; 2 of these had cognitive impairment. One family member with the SPG6del alone had neither HSP nor cognitive impairment. The index case with both deletions died with dementia; the brain showed widespread ubiquitin positivity within the neocortex and white matter. CONCLUSION: Cognitive decline and dementia is a feature of SPG4-HSP due to a deletion of exon 17 of the spastin gene.

  12. Neuropathological Changes in Brain Cortex and Hippocampus in a Rat Model of Alzheimer’s Disease

    Science.gov (United States)

    Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Roosh, Nahid Rahbar; Omidzahir, Shila

    2011-01-01

    Background: Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Methods: Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and β-amyloid (Aβ) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 µL of Aβ (1-40) into the hippocampal fissure. Results: In the present study, Aβ (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. Aβ injection CA1 caused Aβ deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. Conclusion: We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group. PMID:21725500

  13. Neuropathological changes in brain cortex and hippocampus in a rat model of Alzheimer's disease.

    Science.gov (United States)

    Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Rahbar Rooshandel, Nahid; Omidzahir, Shila

    2011-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and Beta amyloid (ABeta) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 muL of ABeta (1-40) into the hippocampal fissure. In the present study, ABeta (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. ABeta injection CA1 caused ABeta deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group.

  14. Cigarette Smoking Accelerated Brain Aging and Induced Pre-Alzheimer-Like Neuropathology in Rats

    Science.gov (United States)

    Ho, Yuen-Shan; Yang, Xifei; Yeung, Sze-Chun; Chiu, Kin; Lau, Chi-Fai; Tsang, Andrea Wing-Ting; Mak, Judith Choi-Wo; Chang, Raymond Chuen-Chung

    2012-01-01

    Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD). To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD) rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP) processing by increasing the production of sAPPβ and accumulation of β–amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia. PMID:22606286

  15. Regional glucose utilization and blood flow following graded forebrain ischemia in the rat: correlation with neuropathology

    International Nuclear Information System (INIS)

    Ginsberg, M.D.; Graham, D.I.; Busto, R.

    1985-01-01

    Regional patterns of cerebral glucose utilization (rCMRglc) and blood flow (rCBF) were examined in the early recovery period following transient forebrain ischemia in order to correlate early postischemic physiological events with regionally selective patterns of ischemic neuropathology. Wistar rats were subjected to 30 or 60 minutes of graded forebrain ischemia by a method combining unilateral occlusion of the common carotid artery with moderate elevation of intracranial pressure and mild hypotension; this procedure results in a high-grade ischemic deficit affecting chiefly the lateral neocortex, striatum, and hippocampus ipsilateral to the carotid occlusion. Simultaneous measurements of rCMRglc and rCBF made in regional tissue samples after 2 and 4 hours of postischemic recirculation using a double-tracer radioisotopic strategy revealed a disproportionately high level of glucose metabolism relative to blood flow in the early postischemic striatum, owing to the resumption of nearly normal rCMRglc in the face of depressed flow. In contrast, the neocortex, which had been equally ischemic, showed parallel depressions of both metabolism and blood flow during early recovery. Light microscopy at 4 and 8 hours after recovery revealed the striatum to be the predominant locus of ischemic neuronal alterations, whereas neocortical lesions were much less prominent in extent and severity at this time. The resumption of normal levels of metabolism in the setting of a disproportionate depression of rCBF in the early postischemic period may accentuate the process of neuronal injury initiated by ischemia and may contribute to the genesis of neuronal necrosis in selectively vulnerable areas of the forebrain

  16. Early stages of Alzheimer's disease are alarming signs in injury deaths caused by traffic accidents in elderly people (≥60 years of age): A neuropathological study.

    Science.gov (United States)

    Wijesinghe, Printha; Gorrie, Catherine; Shankar, S K; Chickabasaviah, Yasha T; Amaratunga, Dhammika; Hulathduwa, Sanjayah; Kumara, K Sunil; Samarasinghe, Kamani; Suh, Yoo-Hun; Steinbusch, H W M; De Silva, K Ranil D

    2017-01-01

    There is little information available in the literature concerning the contribution of dementia in injury deaths in elderly people (≥60 years). This study was intended to investigate the extent of dementia-related pathologies in the brains of elderly people who died in traffic accidents or by suicide and to compare our findings with age- and sex-matched natural deaths in an elderly population. Autopsy-derived human brain samples from nine injury death victims (5 suicide and 4 traffic accidents) and nine age- and sex-matched natural death victims were screened for neurodegenerative and cerebrovascular pathologies using histopathological and immunohistochemical techniques. For the analysis, Statistical Package for the Social Sciences (SPSS) version 16.0 was used. There was a greater likelihood for Alzheimer's disease (AD)-related changes in the elders who succumbed to traffic accidents (1 out of 4) compared to age- and sex-matched suicides (0 out of 5) or natural deaths (0 out of 9) as assessed by the National Institute on Aging - Alzheimer's Association guidelines. Actual burden of both neurofibrillary tangles (NFTs) and (SPs) was comparatively higher in the brains of traffic accidents, and the mean NFT counts were significantly higher in the region of entorhinal cortex ( P traffic accidents in elderly people whereas suicidal brain neuropathologies resembled natural deaths.

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

    Science.gov (United States)

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

    2009-02-06

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

  18. Fc-Glycosylation in Human IgG1 and IgG3 Is Similar for Both Total and Anti-Red-Blood Cell Anti-K Antibodies

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    Myrthe E. Sonneveld

    2018-01-01

    Full Text Available After albumin, immunoglobulin G (IgG are the most abundant proteins in human serum, with IgG1 and IgG3 being the most abundant subclasses directed against protein antigens. The quality of the IgG-Fc-glycosylation has important functional consequences, which have been found to be skewed toward low fucosylation in some antigen-specific immune responses. This increases the affinity to IgG1-Fc-receptor (FcγRIIIa/b and thereby directly affects downstream effector functions and disease severity. To date, antigen-specific IgG-glycosylation have not been analyzed for IgG3. Here, we analyzed 30 pregnant women with anti-K alloantibodies from a prospective screening cohort and compared the type of Fc-tail glycosylation of total serum- and antigen-specific IgG1 and IgG3 using mass spectrometry. Total serum IgG1 and IgG3 Fc-glycoprofiles were highly similar. Fc glycosylation of antigen-specific IgG varied greatly between individuals, but correlated significantly with each other for IgG1 and IgG3, except for bisection. However, although the magnitude of changes in fucosylation and galactosylation were similar for both subclasses, this was not the case for sialylation levels, which were significantly higher for both total and anti-K IgG3. We found that the combination of relative IgG1 and IgG3 Fc-glycosylation levels did not improve the prediction of anti-K mediated disease over IgG1 alone. In conclusion, Fc-glycosylation profiles of serum- and antigen-specific IgG1 and IgG3 are highly similar.

  19. A Chronic Longitudinal Characterization of Neurobehavioral and Neuropathological Cognitive Impairment in a Mouse Model of Gulf War Agent Exposure

    Science.gov (United States)

    Zakirova, Zuchra; Crynen, Gogce; Hassan, Samira; Abdullah, Laila; Horne, Lauren; Mathura, Venkatarajan; Crawford, Fiona; Ait-Ghezala, Ghania

    2016-01-01

    Gulf War Illness (GWI) is a chronic multisymptom illness with a central nervous system component that includes memory impairment as well as neurological and musculoskeletal deficits. Previous studies have shown that in the First Persian Gulf War conflict (1990–1991) exposure to Gulf War (GW) agents, such as pyridostigmine bromide (PB) and permethrin (PER), were key contributors to the etiology of GWI. For this study, we used our previously established mouse model of GW agent exposure (10 days PB+PER) and undertook an extensive lifelong neurobehavioral characterization of the mice from 11 days to 22.5 months post exposure in order to address the persistence and chronicity of effects suffered by the current GWI patient population, 24 years post-exposure. Mice were evaluated using a battery of neurobehavioral testing paradigms, including Open Field Test (OFT), Elevated Plus Maze (EPM), Three Chamber Testing, Radial Arm Water Maze (RAWM), and Barnes Maze (BM) Test. We also carried out neuropathological analyses at 22.5 months post exposure to GW agents after the final behavioral testing. Our results demonstrate that PB+PER exposed mice exhibit neurobehavioral deficits beginning at the 13 months post exposure time point and continuing trends through the 22.5 month post exposure time point. Furthermore, neuropathological changes, including an increase in GFAP staining in the cerebral cortices of exposed mice, were noted 22.5 months post exposure. Thus, the persistent neuroinflammation evident in our model presents a platform with which to identify novel biological pathways, correlating with emergent outcomes that may be amenable to therapeutic targeting. Furthermore, in this work we confirmed our previous findings that GW agent exposure causes neuropathological changes, and have presented novel data which demonstrate increased disinhibition, and lack of social preference in PB+PER exposed mice at 13 months after exposure. We also extended upon our previous work to

  20. Regional thalamic neuropathology in patients with hippocampal sclerosis and epilepsy: A postmortem study

    Science.gov (United States)

    Sinjab, Barah; Martinian, Lillian; Sisodiya, Sanjay M; Thom, Maria

    2013-01-01

    Purpose Clinical, experimental, and neuroimaging data all indicate that the thalamus is involved in the network of changes associated with temporal lobe epilepsy (TLE), particularly in association with hippocampal sclerosis (HS), with potential roles in seizure initiation and propagation. Pathologic changes in the thalamus may be a result of an initial insult, ongoing seizures, or retrograde degeneration through reciprocal connections between thalamic and limbic regions. Our aim was to carry out a neuropathologic analysis of the thalamus in a postmortem (PM) epilepsy series, to assess the distribution, severity, and nature of pathologic changes and its association with HS. Methods Twenty-four epilepsy PM cases (age range 25–87 years) and eight controls (age range 38–85 years) were studied. HS was classified as unilateral (UHS, 11 cases), bilateral (BHS, 4 cases) or absent (No-HS, 9 cases). Samples from the left and right sides of the thalamus were stained with cresyl violet (CV), and for glial firbillary acidic protein (GFAP) and synaptophysin. Using image analysis, neuronal densities (NDs) or field fraction staining values (GFAP, synaptophysin) were measured in four thalamic nuclei: anteroventral nucleus (AV), lateral dorsal nucleus (LD), mediodorsal nucleus (MD), and ventrolateral nucleus (VL). The results were compared within and between cases. Key Findings The severity, nature, and distribution of thalamic pathology varied between cases. A pattern that emerged was a preferential involvement of the MD in UHS cases with a reduction in mean ND ipsilateral to the side of HS (p = 0.05). In UHS cases, greater field fraction values for GFAP and lower values for synaptophysin and ND were seen in the majority of cases in the MD ipsilateral to the side of sclerosis compared to other thalamic nuclei. In addition, differences in the mean ND between classical HS, atypical HS, and No-HS cases were noted in the ipsilateral MD (p < 0.05), with lower values observed in

  1. Vascular cognitive impairment neuropathology guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment.

    Science.gov (United States)

    Skrobot, Olivia A; Attems, Johannes; Esiri, Margaret; Hortobágyi, Tibor; Ironside, James W; Kalaria, Rajesh N; King, Andrew; Lammie, George A; Mann, David; Neal, James; Ben-Shlomo, Yoav; Kehoe, Patrick G; Love, Seth

    2016-11-01

    There are no generally accepted protocols for post-mortem assessment in cases of suspected vascular cognitive impairment. Neuropathologists from seven UK centres have collaborated in the development of a set of vascular cognitive impairment neuropathology guidelines (VCING), representing a validated consensus approach to the post-mortem assessment and scoring of cerebrovascular disease in relation to vascular cognitive impairment. The development had three stages: (i) agreement on a sampling protocol and scoring criteria, through a series of Delphi method surveys; (ii) determination of inter-rater reliability for each type of pathology in each region sampled (Gwet's AC2 coefficient); and (iii) empirical testing and validation of the criteria, by blinded post-mortem assessment of brain tissue from 113 individuals (55 to 100 years) without significant neurodegenerative disease who had had formal cognitive assessments within 12 months of death. Fourteen different vessel and parenchymal pathologies were assessed in 13 brain regions. Almost perfect agreement (AC2 > 0.8) was found when the agreed criteria were used for assessment of leptomeningeal, cortical and capillary cerebral amyloid angiopathy, large infarcts, lacunar infarcts, microhaemorrhage, larger haemorrhage, fibrinoid necrosis, microaneurysms, perivascular space dilation, perivascular haemosiderin leakage, and myelin loss. There was more variability (but still reasonably good agreement) in assessment of the severity of arteriolosclerosis (0.45-0.91) and microinfarcts (0.52-0.84). Regression analyses were undertaken to identify the best predictors of cognitive impairment. Seven pathologies-leptomeningeal cerebral amyloid angiopathy, large infarcts, lacunar infarcts, microinfarcts, arteriolosclerosis, perivascular space dilation and myelin loss-predicted cognitive impairment. Multivariable logistic regression determined the best predictive models of cognitive impairment. The preferred model included moderate

  2. Alzheimer neuropathology without frontotemporal lobar degeneration hallmarks (TAR DNA-binding protein 43 inclusions) in missense progranulin mutation Cys139Arg.

    Science.gov (United States)

    Redaelli, Veronica; Rossi, Giacomina; Maderna, Emanuela; Kovacs, Gabor G; Piccoli, Elena; Caroppo, Paola; Cacciatore, Francesca; Spinello, Sonia; Grisoli, Marina; Sozzi, Giuliano; Salmaggi, Andrea; Tagliavini, Fabrizio; Giaccone, Giorgio

    2018-01-01

    Null mutations in progranulin gene (GRN) reduce the progranulin production resulting in haploinsufficiency and are tightly associated with tau-negative frontotemporal lobar degeneration with TAR DNA-binding protein 43-positive inclusions (FTLD-TDP). Missense mutations of GRN were also identified, but their effects are not completely clear, in particular unanswered is the question of what neuropathology they elicit, also considering that their occurrence has been reported in patients with typical clinical features of Alzheimer disease. They describe two fraternal twins carrying the missense GRN Cys139Arg mutation affected by late-onset dementia and we report the neuropathological study of one of them. Both patients were examined by neuroimaging, neuropsychological assessment and genetic analysis of GRN and other genes associated with dementia. The brain of one was obtained at autopsy and examined neuropathologically. One sister presented clinical and MRI features leading to the diagnosis of Alzheimer disease. The other underwent autopsy and the brain showed neuropathological hallmarks of Alzheimer disease with abundant Aβ-amyloid deposition and Braak stage V of neurofibrillary pathology, in the absence of the hallmark lesions of FTLD-TDP. Their findings may contribute to better clarify the role of progranulin in neurodegenerative diseases indicating that some GRN mutations, in particular missense ones, may act as strong risk factor for Alzheimer disease rather than induce FTLD-TDP. © 2016 International Society of Neuropathology.

  3. A quantitative study of the neuropathology of 32 sporadic and familial cases of frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP).

    Science.gov (United States)

    Armstrong, R A; Carter, D; Cairns, N J

    2012-02-01

    To further characterize the neuropathology of the heterogeneous molecular disorder frontotemporal lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). We quantified the neuronal cytoplasmic inclusions, glial inclusions, neuronal intranuclear inclusions, dystrophic neurites, surviving neurones, abnormally enlarged neurones, and vacuoles in regions of the frontal and temporal lobe using a phosphorylation-independent TDP-43 antibody in 32 cases of FTLD-TDP comprising sporadic and familial cases, with associated pathology such as hippocampal sclerosis (HS) or Alzheimer's disease (AD), and four neuropathological subtypes using TDP-43 immunohistochemistry. Analysis of variance (anova) was used to compare differences between the various groups of cases. These data from FTLD-TDP cases demonstrate quantitative differences in pathological features between: (i) regions of the frontal and temporal lobe; (ii) upper and lower cortex; (iii) sporadic and progranulin (GRN) mutation cases; (iv) cases with and without AD or HS; and (v) between assigned subtypes. The data confirm that the dentate gyrus is a major site of neuropathology in FTLD-TDP and that most laminae of the cerebral cortex are affected. GRN mutation cases are quantitatively different from sporadic cases, while cases with associated HS and AD have increased densities of dystrophic neurites and abnormally enlarged neurones respectively. There is little correlation between the subjective assessment of subtypes and the more objective quantitative data. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

  4. Aerosol exposure to Rift Valley fever virus causes earlier and more severe neuropathology in the murine model, which has important implications for therapeutic development.

    Directory of Open Access Journals (Sweden)

    Christopher Reed

    Full Text Available Rift Valley fever virus (RVFV is an important mosquito-borne veterinary and human pathogen that can cause severe disease including acute-onset hepatitis, delayed-onset encephalitis, retinitis and blindness, or a hemorrhagic syndrome. Currently, no licensed vaccine or therapeutics exist to treat this potentially deadly disease. Detailed studies describing the pathogenesis of RVFV following aerosol exposure have not been completed and candidate therapeutics have not been evaluated following an aerosol exposure. These studies are important because while mosquito transmission is the primary means for human infection, it can also be transmitted by aerosol or through mucosal contact. Therefore, we directly compared the pathogenesis of RVFV following aerosol exposure to a subcutaneous (SC exposure in the murine model by analyzing survival, clinical observations, blood chemistry, hematology, immunohistochemistry, and virus titration of tissues. Additionally, we evaluated the effectiveness of the nucleoside analog ribavirin administered prophylactically to treat mice exposed by aerosol and SC. The route of exposure did not significantly affect the survival, chemistry or hematology results of the mice. Acute hepatitis occurred despite the route of exposure. However, the development of neuropathology occurred much earlier and was more severe in mice exposed by aerosol compared to SC exposed mice. Mice treated with ribavirin and exposed SC were partially protected, whereas treated mice exposed by aerosol were not protected. Early and aggressive viral invasion of brain tissues following aerosol exposure likely played an important role in ribavirin's failure to prevent mortality among these animals. Our results highlight the need for more candidate antivirals to treat RVFV infection, especially in the case of a potential aerosol exposure. Additionally, our study provides an account of the key pathogenetic differences in RVF disease following two potential

  5. The small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma and full-length FOXP1 exert similar oncogenic and transcriptional activity in human B cells.

    Science.gov (United States)

    van Keimpema, Martine; Grüneberg, Leonie J; Schilder-Tol, Esther J M; Oud, Monique E C M; Beuling, Esther A; Hensbergen, Paul J; de Jong, Johann; Pals, Steven T; Spaargaren, Marcel

    2017-03-01

    The forkhead transcription factor FOXP1 is generally regarded as an oncogene in activated B cell-like diffuse large B-cell lymphoma. Previous studies have suggested that a small isoform of FOXP1 rather than full-length FOXP1, may possess this oncogenic activity. Corroborating those studies, we herein show that activated B cell-like diffuse large B-cell lymphoma cell lines and primary activated B cell-like diffuse large B-cell lymphoma cells predominantly express a small FOXP1 isoform, and that the 5'-end of the Foxp1 gene is a common insertion site in murine lymphomas in leukemia virus- and transposon-mediated insertional mutagenesis screens. By combined mass spectrometry, (quantative) reverse transcription polymerase chain reaction/sequencing, and small interfering ribonucleic acid-mediated gene silencing, we determined that the small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma lacks the N-terminal 100 amino acids of full-length FOXP1. Aberrant overexpression of this FOXP1 isoform (ΔN100) in primary human B cells revealed its oncogenic capacity; it repressed apoptosis and plasma cell differentiation. However, no difference in potency was found between this small FOXP1 isoform and full-length FOXP1. Furthermore, overexpression of full-length FOXP1 or this small FOXP1 isoform in primary B cells and diffuse large B-cell lymphoma cell lines resulted in similar gene regulation. Taken together, our data indicate that this small FOXP1 isoform and full-length FOXP1 have comparable oncogenic and transcriptional activity in human B cells, suggesting that aberrant expression or overexpression of FOXP1, irrespective of the specific isoform, contributes to lymphomagenesis. These novel insights further enhance the value of FOXP1 for the diagnostics, prognostics, and treatment of diffuse large B-cell lymphoma patients. Copyright© Ferrata Storti Foundation.

  6. Linguistic ability in early life and the neuropathology of Alzheimer's disease and cerebrovascular disease. Findings from the Nun Study.

    Science.gov (United States)

    Snowdon, D A; Greiner, L H; Markesbery, W R

    2000-04-01

    Findings from the Nun Study indicate that low linguistic ability in early life has a strong association with dementia and premature death in late life. In the present study, we investigated the relationship of linguistic ability in early life to the neuropathology of Alzheimer's disease and cerebrovascular disease. The analyses were done on a subset of 74 participants in the Nun Study for whom we had handwritten autobiographies completed some time between the ages of 19 and 37 (mean = 23 years). An average of 62 years after writing the autobiographies, when the participants were 78 to 97 years old, they died and their brains were removed for our neuropathologic studies. Linguistic ability in early life was measured by the idea (proposition) density of the autobiographies, i.e., a standard measure of the content of ideas in text samples. Idea density scores from early life had strong inverse correlations with the severity of Alzheimer's disease pathology in the neocortex: Correlations between idea density scores and neurofibrillary tangle counts were -0.59 for the frontal lobe, -0.48 for the temporal lobe, and -0.49 for the parietal lobe (all p values < 0.0001). Idea density scores were unrelated to the severity of atherosclerosis of the major arteries at the base of the brain and to the presence of lacunar and large brain infarcts. Low linguistic ability in early life may reflect suboptimal neurological and cognitive development, which might increase susceptibility to the development of Alzheimer's disease pathology in late life.

  7. The Utility of Expert Diagnosis in Surgical Neuropathology: Analysis of Consultations Reviewed at 5 National Comprehensive Cancer Network Institutions.

    Science.gov (United States)

    Bruner, Janet M; Louis, David N; McLendon, Roger; Rosenblum, Marc K; Archambault, W Tad; Most, Susan; Tihan, Tarik

    2017-03-01

    The aim of this study was to characterize the type and degree of discrepancies between non-expert and expert diagnoses of CNS tumors to identify the value of consultations in surgical neuropathology. Neuropathology experts from 5 National Comprehensive Cancer Network (NCCN) member institutions participated in the review of 1281 consultations selected based on inclusion criteria. The consultation cases were re-reviewed at the NCCN headquarters to determine concordance with the original diagnoses. Among all consultations, 249 (19.4%) were submitted for expert diagnoses without final diagnoses from the submitting institution. Within the remaining 1032 patients, the serious/major discrepancy rate was 4.8%, and less serious and minor discrepancies were seen in 19.4% of the cases. The discrepancy rate was higher among patients who were referred to NCCN institutions for consultation compared to those who were referred for treatment only. The discrepancy rates, patient demographics, type of consultations and submitting institutions varied among participating NCCN institutions. Expert consultations identified a subset of cases with significant diagnostic discrepancies, and constituted the initial diagnoses in some cases. These data indicate that expert consultations in glial tumors and all types of pediatric CNS tumors can improve accurate diagnosis and enable appropriate management. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  8. Identification of genes associated with dissociation of cognitive performance and neuropathological burden: Multistep analysis of genetic, epigenetic, and transcriptional data.

    Directory of Open Access Journals (Sweden)

    Charles C White

    2017-04-01

    Full Text Available The molecular underpinnings of the dissociation of cognitive performance and neuropathological burden are poorly understood, and there are currently no known genetic or epigenetic determinants of the dissociation."Residual cognition" was quantified by regressing out the effects of cerebral pathologies and demographic characteristics on global cognitive performance proximate to death. To identify genes influencing residual cognition, we leveraged neuropathological, genetic, epigenetic, and transcriptional data available for deceased participants of the Religious Orders Study (n = 492 and the Rush Memory and Aging Project (n = 487. Given that our sample size was underpowered to detect genome-wide significance, we applied a multistep approach to identify genes influencing residual cognition, based on our prior observation that independent genetic and epigenetic risk factors can converge on the same locus. In the first step (n = 979, we performed a genome-wide association study with a predefined suggestive p < 10-5, and nine independent loci met this threshold in eight distinct chromosomal regions. Three of the six genes within 100 kb of the lead SNP are expressed in the dorsolateral prefrontal cortex (DLPFC: UNC5C, ENC1, and TMEM106B. In the second step, in the subset of participants with DLPFC DNA methylation data (n = 648, we found that residual cognition was related to differential DNA methylation of UNC5C and ENC1 (false discovery rate < 0.05. In the third step, in the subset of participants with DLPFC RNA sequencing data (n = 469, brain transcription levels of UNC5C and ENC1 were evaluated for their association with residual cognition: RNA levels of both UNC5C (estimated effect = -0.40, 95% CI -0.69 to -0.10, p = 0.0089 and ENC1 (estimated effect = 0.0064, 95% CI 0.0033 to 0.0096, p = 5.7 × 10-5 were associated with residual cognition. In secondary analyses, we explored the mechanism of these associations and found that ENC1 may be related to

  9. A neural cell adhesion molecule-derived peptide reduces neuropathological signs and cognitive impairment induced by Abeta25-35

    DEFF Research Database (Denmark)

    Klementiev, B; Novikova, T; Novitskaya, V

    2007-01-01

    death and brain atrophy in response to Abeta25-35. Finally, the Abeta25-35-administration led to a reduced short-term memory as determined by the social recognition test. A synthetic peptide termed FGL derived from the neural cell adhesion molecule (NCAM) was able to prevent or, if already manifest......, strongly reduce all investigated signs of Abeta25-35-induced neuropathology and cognitive impairment. The FGL peptide was recently demonstrated to be able to cross the blood-brain-barrier. Accordingly, we found that the beneficial effects of FGL were achieved not only by intracisternal, but also...... and cognitive impairment involves the modulation of intracellular signal-transduction mediated through GSK3beta....

  10. Effects of apolipoprotein E genotype on cortical neuropathology in senile dementia of the Lewy body and Alzheimer's disease.

    Science.gov (United States)

    Benjamin, R; Leake, A; Ince, P G; Perry, R H; McKeith, I G; Edwardson, J A; Morris, C M

    1995-12-01

    Apolipoprotein E (APO E) genotypes were determined in a UK population of neuropathologically confirmed control cases, and in cases of Lewy body dementia (SDLT) and late onset Alzheimer's disease (AD). APO E epsilon 4 allele frequency was significantly elevated in both SDLT and AD groups with a concomitant reduction in the APO E epsilon 3 allele frequency. The epsilon 2 allele frequency in the AD group was only 25% of the control population, though because of the relatively small sample size this reduction was not significant; the epsilon 2 allele frequency in the SDLT group was normal. No significant association was found between senile plaque density and neurofibrillary tangle density in the neocortex and APO E allele dose in either SDLT or AD. Although the possession of APO E epsilon 4 is associated with an increased risk of developing SDLT and AD, actual APO E genotype does not appear to affect the burden of pathology.

  11. Cross-kingdom similarities in microbiome functions

    NARCIS (Netherlands)

    Mendes, R.; Raaijmakers, J.M.

    2015-01-01

    Recent advances in medical research have revealed how humans rely on their microbiome for diverse traits and functions. Similarly, microbiomes of other higher organisms play key roles in disease, health, growth and development of their host. Exploring microbiome functions across kingdoms holds

  12. Reduced Number of Pigmented Neurons in the Substantia Nigra of Dystonia Patients? Findings from Extensive Neuropathologic, Immunohistochemistry, and Quantitative Analyses

    Directory of Open Access Journals (Sweden)

    Diego Iacono

    2015-05-01

    Full Text Available Background: Dystonias (Dys represent the third most common movement disorder after essential tremor (ET and Parkinson's disease (PD. While some pathogenetic mechanisms and genetic causes of Dys have been identified, little is known about their neuropathologic features. Previous neuropathologic studies have reported generically defined neuronal loss in various cerebral regions of Dys brains, mostly in the basal ganglia (BG, and specifically in the substantia nigra (SN. Enlarged pigmented neurons in the SN of Dys patients with and without specific genetic mutations (e.g., GAG deletions in DYT1 dystonia have also been described. Whether or not Dys brains are associated with decreased numbers or other morphometric changes of specific neuronal types is unknown and has never been addressed with quantitative methodologies. Methods: Quantitative immunohistochemistry protocols were used to estimate neuronal counts and volumes of nigral pigmented neurons in 13 SN of Dys patients and 13 SN of age‐matched control subjects (C. Results: We observed a significant reduction (∼20% of pigmented neurons in the SN of Dys compared to C (p<0.01. Neither significant volumetric changes nor evident neurodegenerative signs were observed in the remaining pool of nigral pigmented neurons in Dys brains. These novel quantitative findings were confirmed after exclusion of possible co‐occurring SN pathologies including Lewy pathology, tau‐neurofibrillary tangles, β‐amyloid deposits, ubiquitin (ubiq, and phosphorylated‐TAR DNA‐binding protein 43 (pTDP43‐positive inclusions. Discussion: A reduced number of nigral pigmented neurons in the absence of evident neurodegenerative signs in Dys brains could indicate previously unconsidered pathogenetic mechanisms of Dys such as neurodevelopmental defects in the SN.

  13. Gene-wise association of variants in four lysosomal storage disorder genes in neuropathologically confirmed Lewy body disease.

    Science.gov (United States)

    Clark, Lorraine N; Chan, Robin; Cheng, Rong; Liu, Xinmin; Park, Naeun; Parmalee, Nancy; Kisselev, Sergey; Cortes, Etty; Torres, Paola A; Pastores, Gregory M; Vonsattel, Jean P; Alcalay, Roy; Marder, Karen; Honig, Lawrence L; Fahn, Stanley; Mayeux, Richard; Shelanski, Michael; Di Paolo, Gilbert; Lee, Joseph H

    2015-01-01

    Variants in GBA are associated with Lewy Body (LB) pathology. We investigated whether variants in other lysosomal storage disorder (LSD) genes also contribute to disease pathogenesis. We performed a genetic analysis of four LSD genes including GBA, HEXA, SMPD1, and MCOLN1 in 231 brain autopsies. Brain autopsies included neuropathologically defined LBD without Alzheimer Disease (AD) changes (n = 59), AD without significant LB pathology (n = 71), Alzheimer disease and lewy body variant (ADLBV) (n = 68), and control brains without LB or AD neuropathology (n = 33). Sequencing of HEXA, SMPD1, MCOLN1 and GBA followed by 'gene wise' genetic association analysis was performed. To determine the functional effect, a biochemical analysis of GBA in a subset of brains was also performed. GCase activity was measured in a subset of brain samples (n = 64) that included LBD brains, with or without GBA mutations, and control brains. A lipidomic analysis was also performed in brain autopsies (n = 67) which included LBD (n = 34), ADLBV (n = 3), AD (n = 4), PD (n = 9) and control brains (n = 17), comparing GBA mutation carriers to non-carriers. In a 'gene-wise' analysis, variants in GBA, SMPD1 and MCOLN1 were significantly associated with LB pathology (p range: 0.03-4.14 x10(-5)). Overall, the mean levels of GCase activity were significantly lower in GBA mutation carriers compared to non-carriers (plipid classes, ceramides and sphingolipids, was observed in LBD brains carrying GBA mutations compared to controls (p range: p<0.05-p<0.01). Our study indicates that variants in GBA, SMPD1 and MCOLN1 are associated with LB pathology. Biochemical data comparing GBA mutation carrier to non-carriers support these findings, which have important implications for biomarker development and therapeutic strategies.

  14. Gene-wise association of variants in four lysosomal storage disorder genes in neuropathologically confirmed Lewy body disease.

    Directory of Open Access Journals (Sweden)

    Lorraine N Clark

    Full Text Available Variants in GBA are associated with Lewy Body (LB pathology. We investigated whether variants in other lysosomal storage disorder (LSD genes also contribute to disease pathogenesis.We performed a genetic analysis of four LSD genes including GBA, HEXA, SMPD1, and MCOLN1 in 231 brain autopsies. Brain autopsies included neuropathologically defined LBD without Alzheimer Disease (AD changes (n = 59, AD without significant LB pathology (n = 71, Alzheimer disease and lewy body variant (ADLBV (n = 68, and control brains without LB or AD neuropathology (n = 33. Sequencing of HEXA, SMPD1, MCOLN1 and GBA followed by 'gene wise' genetic association analysis was performed. To determine the functional effect, a biochemical analysis of GBA in a subset of brains was also performed. GCase activity was measured in a subset of brain samples (n = 64 that included LBD brains, with or without GBA mutations, and control brains. A lipidomic analysis was also performed in brain autopsies (n = 67 which included LBD (n = 34, ADLBV (n = 3, AD (n = 4, PD (n = 9 and control brains (n = 17, comparing GBA mutation carriers to non-carriers.In a 'gene-wise' analysis, variants in GBA, SMPD1 and MCOLN1 were significantly associated with LB pathology (p range: 0.03-4.14 x10(-5. Overall, the mean levels of GCase activity were significantly lower in GBA mutation carriers compared to non-carriers (p<0.001. A significant increase and accumulation of several species for the lipid classes, ceramides and sphingolipids, was observed in LBD brains carrying GBA mutations compared to controls (p range: p<0.05-p<0.01.Our study indicates that variants in GBA, SMPD1 and MCOLN1 are associated with LB pathology. Biochemical data comparing GBA mutation carrier to non-carriers support these findings, which have important implications for biomarker development and therapeutic strategies.

  15. Pitfalls in the use of whole slide imaging for the diagnosis of central nervous system tumors: A pilot study in surgical neuropathology

    Directory of Open Access Journals (Sweden)

    Melike Pekmezci

    2016-01-01

    Full Text Available Background: Whole slide imaging (WSI finds increasingly higher value in everyday surgical pathology in addition to its well-established use for educational and research purposes. However, its diagnostic utility, especially in subspecialty settings such as neuropathology, is not fully validated. Neuropathology practice is unique with smaller overall tissue size and frequent need for high-power evaluation. In addition, tumor grade is an integral part of the initial diagnosis. The purpose of this study is to assess the feasibility of primary pathology diagnosis of surgical neuropathology specimens using WSI. Materials and Methods: We reviewed consecutive surgical neuropathology cases diagnosed in our institution during a 2-month period and identified a single diagnostic slide, which was scanned at 40× magnification. Two neuropathologists who were blinded to the original diagnoses reviewed the whole slide image and rendered a diagnosis including tumor grade when applicable. They reviewed the single diagnostic slide after a wash-out period. Intra- and inter-observer discrepancies, as well as reasons for discrepancies, were evaluated. Results: The concordance rates were 94.9% and 88% for two neuropathologists. Two critical issues leading to discrepancies were identified: (1 identification of mitoses and (2 recognition of nuclear details. Conclusions: Given the current study is exclusively for surgical neuropathology cases, an all-encompassing conclusion about the utility of WSI for diagnostic purposes may not be available. Nevertheless, pathologists should be aware of the potential pitfalls due to identification of mitotic figures and nuclear details. We recommend independent validation for each subspecialty of pathology to identify subspecialty-specific concerns, so they can be properly addressed.

  16. Injury Response of Resected Human Brain Tissue In Vitro

    NARCIS (Netherlands)

    Verwer, Ronald W. H.; Sluiter, Arja A.; Balesar, Rawien A.; Baaijen, Johannes C.; de Witt Hamer, Philip C.; Speijer, Dave; Li, Yichen; Swaab, Dick F.

    2015-01-01

    Brain injury affects a significant number of people each year. Organotypic cultures from resected normal neocortical tissue provide unique opportunities to study the cellular and neuropathological consequences of severe injury of adult human brain tissue in vitro. The in vitro injuries caused by

  17. Renewing the Respect for Similarity

    Directory of Open Access Journals (Sweden)

    Shimon eEdelman

    2012-07-01

    Full Text Available In psychology, the concept of similarity has traditionally evoked a mixture of respect, stemmingfrom its ubiquity and intuitive appeal, and concern, due to its dependence on the framing of the problemat hand and on its context. We argue for a renewed focus on similarity as an explanatory concept, bysurveying established results and new developments in the theory and methods of similarity-preservingassociative lookup and dimensionality reduction — critical components of many cognitive functions, aswell as of intelligent data management in computer vision. We focus in particular on the growing familyof algorithms that support associative memory by performing hashing that respects local similarity, andon the uses of similarity in representing structured objects and scenes. Insofar as these similarity-basedideas and methods are useful in cognitive modeling and in AI applications, they should be included inthe core conceptual toolkit of computational neuroscience.

  18. Self-similar cosmological models

    Energy Technology Data Exchange (ETDEWEB)

    Chao, W Z [Cambridge Univ. (UK). Dept. of Applied Mathematics and Theoretical Physics

    1981-07-01

    The kinematics and dynamics of self-similar cosmological models are discussed. The degrees of freedom of the solutions of Einstein's equations for different types of models are listed. The relation between kinematic quantities and the classifications of the self-similarity group is examined. All dust local rotational symmetry models have been found.

  19. Self-similar factor approximants

    International Nuclear Information System (INIS)

    Gluzman, S.; Yukalov, V.I.; Sornette, D.

    2003-01-01

    The problem of reconstructing functions from their asymptotic expansions in powers of a small variable is addressed by deriving an improved type of approximants. The derivation is based on the self-similar approximation theory, which presents the passage from one approximant to another as the motion realized by a dynamical system with the property of group self-similarity. The derived approximants, because of their form, are called self-similar factor approximants. These complement the obtained earlier self-similar exponential approximants and self-similar root approximants. The specific feature of self-similar factor approximants is that their control functions, providing convergence of the computational algorithm, are completely defined from the accuracy-through-order conditions. These approximants contain the Pade approximants as a particular case, and in some limit they can be reduced to the self-similar exponential approximants previously introduced by two of us. It is proved that the self-similar factor approximants are able to reproduce exactly a wide class of functions, which include a variety of nonalgebraic functions. For other functions, not pertaining to this exactly reproducible class, the factor approximants provide very accurate approximations, whose accuracy surpasses significantly that of the most accurate Pade approximants. This is illustrated by a number of examples showing the generality and accuracy of the factor approximants even when conventional techniques meet serious difficulties

  20. Dynamic similarity in erosional processes

    Science.gov (United States)

    Scheidegger, A.E.

    1963-01-01

    A study is made of the dynamic similarity conditions obtaining in a variety of erosional processes. The pertinent equations for each type of process are written in dimensionless form; the similarity conditions can then easily be deduced. The processes treated are: raindrop action, slope evolution and river erosion. ?? 1963 Istituto Geofisico Italiano.

  1. Personalized recommendation with corrected similarity

    International Nuclear Information System (INIS)

    Zhu, Xuzhen; Tian, Hui; Cai, Shimin

    2014-01-01

    Personalized recommendation has attracted a surge of interdisciplinary research. Especially, similarity-based methods in applications of real recommendation systems have achieved great success. However, the computations of similarities are overestimated or underestimated, in particular because of the defective strategy of unidirectional similarity estimation. In this paper, we solve this drawback by leveraging mutual correction of forward and backward similarity estimations, and propose a new personalized recommendation index, i.e., corrected similarity based inference (CSI). Through extensive experiments on four benchmark datasets, the results show a greater improvement of CSI in comparison with these mainstream baselines. And a detailed analysis is presented to unveil and understand the origin of such difference between CSI and mainstream indices. (paper)

  2. Vacuolating encephalitis in mice infected by human coronavirus OC43

    International Nuclear Information System (INIS)

    Jacomy, Helene; Talbot, Pierre J.

    2003-01-01

    Involvement of viruses in human neurodegenerative diseases and the underlying pathologic mechanisms remain generally unclear. Human respiratory coronaviruses (HCoV) can infect neural cells, persist in human brain, and activate myelin-reactive T cells. As a means of understanding the human infection, we characterized in vivo the neurotropic and neuroinvasive properties of HCoV-OC43 through the development of an experimental animal model. Virus inoculation of 21-day postnatal C57BL/6 and BALB/c mice led to a generalized infection of the whole CNS, demonstrating HCoV-OC43 neuroinvasiveness and neurovirulence. This acute infection targeted neurons, which underwent vacuolation and degeneration while infected regions presented strong microglial reactivity and inflammatory reactions. Damage to the CNS was not immunologically mediated and microglial reactivity was instead a consequence of direct virus-mediated neuronal injury. Although this acute encephalitis appears generally similar to that induced by murine coronaviruses, an important difference rests in the prominent spongiform-like degeneration that could trigger neuropathology in surviving animals

  3. Towards Personalized Medicine: Leveraging Patient Similarity and Drug Similarity Analytics

    Science.gov (United States)

    Zhang, Ping; Wang, Fei; Hu, Jianying; Sorrentino, Robert

    2014-01-01

    The rapid adoption of electronic health records (EHR) provides a comprehensive source for exploratory and predictive analytic to support clinical decision-making. In this paper, we investigate how to utilize EHR to tailor treatments to individual patients based on their likelihood to respond to a therapy. We construct a heterogeneous graph which includes two domains (patients and drugs) and encodes three relationships (patient similarity, drug similarity, and patient-drug prior associations). We describe a novel approach for performing a label propagation procedure to spread the label information representing the effectiveness of different drugs for different patients over this heterogeneous graph. The proposed method has been applied on a real-world EHR dataset to help identify personalized treatments for hypercholesterolemia. The experimental results demonstrate the effectiveness of the approach and suggest that the combination of appropriate patient similarity and drug similarity analytics could lead to actionable insights for personalized medicine. Particularly, by leveraging drug similarity in combination with patient similarity, our method could perform well even on new or rarely used drugs for which there are few records of known past performance. PMID:25717413

  4. Glial adenosine kinase--a neuropathological marker of the epileptic brain

    NARCIS (Netherlands)

    Aronica, Eleonora; Sandau, Ursula S.; Iyer, Anand; Boison, Detlev

    2013-01-01

    Experimental research over the past decade has supported the critical role of astrocytes activated by different types of injury and the pathophysiological processes that underlie the development of epilepsy. In both experimental and human epileptic tissues astrocytes undergo complex changes in their

  5. [Does Alzheimer's disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (II)].

    Science.gov (United States)

    Toledano, A; Álvarez, M I; López-Rodríguez, A B; Toledano-Díaz, A; Fernández-Verdecia, C I

    2014-01-01

    In the ageing process there are some species of non-human primates which can show some of the defining characteristics of the Alzheimer's disease (AD) of man, both in neuropathological changes and cognitive-behavioural symptoms. The study of these species is of prime importance to understand AD and develop therapies to combat this neurodegenerative disease. In this second part of the study, these AD features are discussed in the most important non-experimental AD models (Mouse Lemur -Microcebus murinus, Caribbean vervet -Chlorocebus aethiops, and the Rhesus and stump-tailed macaque -Macaca mulatta and M. arctoides) and experimental models (lesional, neurotoxic, pharmacological, immunological, etc.) non-human primates. In all these models cerebral amyloid neuropathology can occur in senility, although with different levels of incidence (100% in vervets;primates, such as the macaque, the existence of a possible continuum between "normal" ageing process, "normal" ageing with no deep neuropathological and cognitive-behavioural changes, and "pathological ageing" (or "Alzheimer type ageing"), may be considered. In other cases, such as the Caribbean vervet, neuropathological changes are constant and quite marked, but its impact on cognition and behaviour does not seem to be very important. This does assume the possible existence in the human senile physiological regression of a stable phase without dementia even if neuropathological changes appeared. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  6. Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: A nontargeted metabolomic study.

    Directory of Open Access Journals (Sweden)

    Stuart G Snowden

    2017-03-01

    Full Text Available The metabolic basis of Alzheimer disease (AD pathology and expression of AD symptoms is poorly understood. Omega-3 and -6 fatty acids have previously been linked to both protective and pathogenic effects in AD. However, to date little is known about how the abundance of these species is affected by differing levels of disease pathology in the brain.We performed metabolic profiling on brain tissue samples from 43 individuals ranging in age from 57 to 95 y old who were stratified into three groups: AD (N = 14, controls (N = 14 and "asymptomatic Alzheimer's disease" (ASYMAD, i.e., individuals with significant AD neuropathology at death but without evidence for cognitive impairment during life (N = 15 from the autopsy sample of the Baltimore Longitudinal Study of Aging (BLSA. We measured 4,897 metabolite features in regions both vulnerable in the middle frontal and inferior temporal gyri (MFG and ITG and resistant (cerebellum to classical AD pathology. The levels of six unsaturated fatty acids (UFAs in whole brain were compared in controls versus AD, and the differences were as follows: linoleic acid (p = 8.8 x 10-8, FC = 0.52, q = 1.03 x 10-6, linolenic acid (p = 2.5 x 10-4, FC = 0.84, q = 4.03 x 10-4, docosahexaenoic acid (p = 1.7 x 10-7, FC = 1.45, q = 1.24 x 10-6, eicosapentaenoic acid (p = 4.4 x 10-4, FC = 0.16, q = 6.48 x 10-4, oleic acid (p = 3.3 x 10-7, FC = 0.34, q = 1.46 x 10-6, and arachidonic acid (p = 2.98 x 10-5, FC = 0.75, q = 7.95 x 10-5. These fatty acids were strongly associated with AD when comparing the groups in the MFG and ITG, respectively: linoleic acid (p ASYMAD>AD and increases in docosahexanoic acid (AD>ASYMAD>control may represent regionally specific threshold levels of these metabolites beyond which the accumulation of AD pathology triggers the expression of clinical symptoms. The main limitation of this study is the relatively small sample size. There are few cohorts with extensive longitudinal cognitive assessments

  7. The neuropathological basis to the functional role of microglia/macrophages in gliomas.

    Science.gov (United States)

    Schiffer, Davide; Mellai, Marta; Bovio, Enrica; Annovazzi, Laura

    2017-09-01

    The paper wants to be a tracking shot of the main recent acquisitions on the function and significance of microglia/macrophages in gliomas. The observations have been principally carried out on in vitro cultures and on tumor transplants in animals. Contrary to what is deduced from microglia in non-neoplastic pathologic conditions of central nervous system (CNS), most conclusions indicate that microglia acts favoring tumor proliferation through an immunosuppression induced by glioma cells. By immunohistochemistry, different microglia phenotypes are recognized in gliomas, from ramified microglia to frank macrophagic aspect. One wonders whether the functional conclusions drawn from many microglia studies, but not in conditions of human pathology, apply to all the phenotypes recognizable in them. It is difficult to verify in human pathology a prognostic significance of microglia. Only CD163-positive microglia/macrophages inversely correlate with glioma patients' survival, whereas the total number of microglia does not change with the malignancy grade.

  8. Domain similarity based orthology detection.

    Science.gov (United States)

    Bitard-Feildel, Tristan; Kemena, Carsten; Greenwood, Jenny M; Bornberg-Bauer, Erich

    2015-05-13

    Orthologous protein detection software mostly uses pairwise comparisons of amino-acid sequences to assert whether two proteins are orthologous or not. Accordingly, when the number of sequences for comparison increases, the number of comparisons to compute grows in a quadratic order. A current challenge of bioinformatic research, especially when taking into account the increasing number of sequenced organisms available, is to make this ever-growing number of comparisons computationally feasible in a reasonable amount of time. We propose to speed up the detection of orthologous proteins by using strings of domains to characterize the proteins. We present two new protein similarity measures, a cosine and a maximal weight matching score based on domain content similarity, and new software, named porthoDom. The qualities of the cosine and the maximal weight matching similarity measures are compared against curated datasets. The measures show that domain content similarities are able to correctly group proteins into their families. Accordingly, the cosine similarity measure is used inside porthoDom, the wrapper developed for proteinortho. porthoDom makes use of domain content similarity measures to group proteins together before searching for orthologs. By using domains instead of amino acid sequences, the reduction of the search space decreases the computational complexity of an all-against-all sequence comparison. We demonstrate that representing and comparing proteins as strings of discrete domains, i.e. as a concatenation of their unique identifiers, allows a drastic simplification of search space. porthoDom has the advantage of speeding up orthology detection while maintaining a degree of accuracy similar to proteinortho. The implementation of porthoDom is released using python and C++ languages and is available under the GNU GPL licence 3 at http://www.bornberglab.org/pages/porthoda .

  9. Similarity measures for face recognition

    CERN Document Server

    Vezzetti, Enrico

    2015-01-01

    Face recognition has several applications, including security, such as (authentication and identification of device users and criminal suspects), and in medicine (corrective surgery and diagnosis). Facial recognition programs rely on algorithms that can compare and compute the similarity between two sets of images. This eBook explains some of the similarity measures used in facial recognition systems in a single volume. Readers will learn about various measures including Minkowski distances, Mahalanobis distances, Hansdorff distances, cosine-based distances, among other methods. The book also summarizes errors that may occur in face recognition methods. Computer scientists "facing face" and looking to select and test different methods of computing similarities will benefit from this book. The book is also useful tool for students undertaking computer vision courses.

  10. Neuropathological findings in entorhinal cortex of subjects aged 50 years or older and their correlation with dementia in a sample from Southern Brazil

    Directory of Open Access Journals (Sweden)

    Edson Rodrigues Neto

    Full Text Available ABSTRACT Introduction: The aims of this study were to survey neurodegenerative changes detected by abnormal protein deposits in the Entorhinal Cortex (EC of subjects aged 50 years or older and to correlate these findings with suspected dementia, as detected by the IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly . Methods: Fourteen brains were submitted to the immunohistochemistry technique for different proteins (beta-amyloid, tau, -synuclein and phospho-TDP-43 and data obtained compared with IQCODE scores. Results: Fifty-seven percent of the individuals exhibited IQCODE results compatible with dementia, being classified into the demented group (DG: 87.5% of patients had neuropathological findings corresponding to Alzheimer's-like brain pathology (ALBP. Of the patients in the non-demented group (NDG, 16.7% met neuropathological criteria for ALBP. All individuals in the DG showed deposits of more than one kind of protein in the EC. The most common association was hyperphosphorylated tau and beta-amyloid protein (87.5%. Discussion: Most individuals with dementia had neuropathological findings of ALBP, as did one individual with no signs of dementia, characterizing a preclinical stage. The results of this study suggest that deposits of a single type of anomalous protein are normal findings in an aging brain, while more than one kind of protein or the combined presence of anomalous protein deposits indicate the presence of dementia.

  11. Neuropathological characteristics of the brain in two patients with SLC19A3 mutations related to the biotin-thiamine-responsive basal ganglia disease

    Directory of Open Access Journals (Sweden)

    Maciej Pronicki

    2017-06-01

    Full Text Available Biotin-thiamine-responsive basal ganglia disease is a severe form of a rare neurogenetic disorder caused by pathogenic molecular variants in the thiamine transporter gene. Nowadays, a potentially effective treatment is known, therefore the early diagnosis is mandatory. The aim of the paper was to assess the contribution of neuropathological and magnetic resonance imaging (MRI studies to a proper diagnosis. We present the brain study of two Polish patients with SLC19A3 mutations, including (1 an infant with an intriguing “walnut” appearance of the brain autopsied many years before the discovery of the SLC19A3 defect, and (2 a one-year-old patient with clinical features of Leigh syndrome. In patient 2, biotin/thiamine responsiveness was not tested at the time of diagnosis and causal treatment started with one-year delay. The central nervous system lesions found in the patients displayed almost clearly a specific pattern for SLC19A3 defect, as previously proposed in diagnostic criteria. Our study presents a detailed description of neuropathological and MRI findings of both patients. We confirm that the autopsy and/or MRI of the brain is sufficient to qualify a patient with an unknown neuropathological disorder directly for SLC19A3 mutations testing and a prompt trial of specific treatment.

  12. Revisiting Inter-Genre Similarity

    DEFF Research Database (Denmark)

    Sturm, Bob L.; Gouyon, Fabien

    2013-01-01

    We revisit the idea of ``inter-genre similarity'' (IGS) for machine learning in general, and music genre recognition in particular. We show analytically that the probability of error for IGS is higher than naive Bayes classification with zero-one loss (NB). We show empirically that IGS does...... not perform well, even for data that satisfies all its assumptions....

  13. Fast business process similarity search

    NARCIS (Netherlands)

    Yan, Z.; Dijkman, R.M.; Grefen, P.W.P.J.

    2012-01-01

    Nowadays, it is common for organizations to maintain collections of hundreds or even thousands of business processes. Techniques exist to search through such a collection, for business process models that are similar to a given query model. However, those techniques compare the query model to each

  14. Glove boxes and similar containments

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    According to the present invention a glove box or similar containment is provided with an exhaust system including a vortex amplifier venting into the system, the vortex amplifier also having its main inlet in fluid flow connection with the containment and a control inlet in fluid flow connection with the atmosphere outside the containment. (U.S.)

  15. Expression of P190 and P210 BCR/ABL1 in normal human CD34(+) cells induces similar gene expression profiles and results in a STAT5-dependent expansion of the erythroid lineage

    DEFF Research Database (Denmark)

    Järås, Marcus; Johnels, Petra; Agerstam, Helena

    2009-01-01

    OBJECTIVE: The P190 and P210 BCR/ABL1 fusion genes are mainly associated with different types of hematologic malignancies, but it is presently unclear whether they are functionally different following expression in primitive human hematopoietic cells. MATERIALS AND METHODS: We investigated...... and systematically compared the effects of retroviral P190 BCR/ABL1 and P210 BCR/ABL1 expression on cell proliferation, differentiation, and global gene expression in human CD34(+) cells from cord blood. RESULTS: Expression of either P190 BCR/ABL1 or P210 BCR/ABL1 resulted in expansion of erythroid cells...... and stimulated erythropoietin-independent burst-forming unit-erythroid colony formation. By using a lentiviral anti-signal transducer and activator of transcription 5 (STAT5) short-hairpin RNA, we found that both P190 BCR/ABL1- and P210 BCR/ABL1-induced erythroid cell expansion were STAT5-dependent. Under...

  16. An Alfven eigenmode similarity experiment

    International Nuclear Information System (INIS)

    Heidbrink, W W; Fredrickson, E; Gorelenkov, N N; Hyatt, A W; Kramer, G; Luo, Y

    2003-01-01

    The major radius dependence of Alfven mode stability is studied by creating plasmas with similar minor radius, shape, magnetic field (0.5 T), density (n e ≅3x10 19 m -3 ), electron temperature (1.0 keV) and beam ion population (near-tangential 80 keV deuterium injection) on both NSTX and DIII-D. The major radius of NSTX is half the major radius of DIII-D. The super-Alfvenic beam ions that drive the modes have overlapping values of v f /v A in the two devices. Observed beam-driven instabilities include toroidicity-induced Alfven eigenmodes (TAE). The stability threshold for the TAE is similar in the two devices. As expected theoretically, the most unstable toroidal mode number n is larger in DIII-D

  17. Similar Symmetries: The Role of Wallpaper Groups in Perceptual Texture Similarity

    Directory of Open Access Journals (Sweden)

    Fraser Halley

    2011-05-01

    Full Text Available Periodic patterns and symmetries are striking visual properties that have been used decoratively around the world throughout human history. Periodic patterns can be mathematically classified into one of 17 different Wallpaper groups, and while computational models have been developed which can extract an image's symmetry group, very little work has been done on how humans perceive these patterns. This study presents the results from a grouping experiment using stimuli from the different wallpaper groups. We find that while different images from the same wallpaper group are perceived as similar to one another, not all groups have the same degree of self-similarity. The similarity relationships between wallpaper groups appear to be dominated by rotations.

  18. Compressional Alfven Eigenmode Similarity Study

    Science.gov (United States)

    Heidbrink, W. W.; Fredrickson, E. D.; Gorelenkov, N. N.; Rhodes, T. L.

    2004-11-01

    NSTX and DIII-D are nearly ideal for Alfven eigenmode (AE) similarity experiments, having similar neutral beams, fast-ion to Alfven speed v_f/v_A, fast-ion pressure, and shape of the plasma, but with a factor of 2 difference in the major radius. Toroidicity-induced AE with ˜100 kHz frequencies were compared in an earlier study [1]; this paper focuses on higher frequency AE with f ˜ 1 MHz. Compressional AE (CAE) on NSTX have a polarization, dependence on the fast-ion distribution function, frequency scaling, and low-frequency limit that are qualitatively consistent with CAE theory [2]. Global AE (GAE) are also observed. On DIII-D, coherent modes in this frequency range are observed during low-field (0.6 T) similarity experiments. Experiments will compare the CAE stability limits on DIII-D with the NSTX stability limits, with the aim of determining if CAE will be excited by alphas in a reactor. Predicted differences in the frequency splitting Δ f between excited modes will also be used. \\vspace0.25em [1] W.W. Heidbrink, et al., Plasmas Phys. Control. Fusion 45, 983 (2003). [2] E.D. Fredrickson, et al., Princeton Plasma Physics Laboratory Report PPPL-3955 (2004).

  19. RNaseT2 knockout rats exhibit hippocampal neuropathology and deficits in memory.

    Science.gov (United States)

    Sinkevicius, Kerstin W; Morrison, Thomas R; Kulkarni, Praveen; Cagliostro, Martha K Caffrey; Iriah, Sade; Malmberg, Samantha; Sabrick, Julia; Honeycutt, Jennifer A; Askew, Kim L; Trivedi, Malav; Ferris, Craig F

    2018-05-10

    RNASET2 deficiency in humans is associated with infant cystic leukoencephalopathy, which causes psychomotor impairment, spasticity, and epilepsy. A zebrafish mutant model suggests that loss of RNASET2 function leads to neurodegeneration due to the accumulation of non-degraded RNA in the lysosomes. The goal of this study was to characterize the first rodent model of RNASET2 deficiency. The brains of 3- and 12-month-old RNaseT2 knockout rats were studied using multiple magnetic resonance imaging modalities and behavioral tests. While T1 and T2 weighted images of RNaseT2 knockout rats exhibited no evidence of cystic lesions, the prefrontal cortex and hippocampal complex were enlarged in knockout animals. Diffusion weighted imaging showed altered anisotropy and putative gray matter changes in the hippocampal complex of the RNaseT2 knockout rats. Immunohistochemistry for glial fibrillary acidic protein (GFAP) showed the presence of hippocampal neuroinflammation. Decreased levels of lysosome-associated membrane protein 2 (LAMP2) and elevated acid phosphatase and β-N-Acetylglucosaminidase (NAG) activities indicated that the RNASET2 knockout rats likely had altered lysosomal function and potential defects in autophagy. Object recognition tests confirmed the RNaseT2 knockout rats exhibited memory deficits. However, the Barnes maze, and balance beam and rotarod tests, indicated there were no differences in spatial memory or motor impairments, respectively. Overall, patients with RNASET2 deficiency exhibited a more severe neurodegeneration phenotype than was observed in the RNaseT2 knockout rats. However, the vulnerability of the knockout rat hippocampus as evidenced by neuroinflammation, altered lysosomal function, and cognitive defects indicates this is still a useful in vivo model to study RNASET2 function. © 2018. Published by The Company of Biologists Ltd.

  20. Lithium improves hippocampal neurogenesis, neuropathology and cognitive functions in APP mutant mice.

    Directory of Open Access Journals (Sweden)

    Anna Fiorentini

    Full Text Available BACKGROUND: Alzheimer's disease (AD is a neurodegenerative disorder characterized by progressive deterioration of cognitive functions, extracellular β-amyloid (Aβ plaques and intracellular neurofibrillary tangles within neocortex and hippocampus. Adult hippocampal neurogenesis plays an important role in learning and memory processes and its abnormal regulation might account for cognitive impairments associated with AD. METHODOLOGY/PRINCIPAL FINDINGS: The double transgenic (Tg CRND8 mice (overexpressing the Swedish and Indiana mutations in the human amyloid precursor protein, aged 2 and 6 months, were used to examine in vivo the effects of 5 weeks lithium treatment. BrdU labelling showed a decreased neurogenesis in the subgranular zone of Tg mice compared to non-Tg mice. The decrease of hippocampal neurogenesis was accompanied by behavioural deficits and worsened with age and pathology severity. The differentiation into neurons and maturation of the proliferating cells were also markedly impaired in the Tg mice. Lithium treatment to 2-month-old Tg mice significantly stimulated the proliferation and neuron fate specification of newborn cells and fully counteracted the transgene-induced impairments of cognitive functions. The drug, by the inhibition of GSK-3β and subsequent activation of Wnt/ß-catenin signalling promoted hippocampal neurogenesis. Finally, the data show that the lithium's ability to stimulate neurogenesis and cognitive functions was lost in the aged Tg mice, thus indicating that the lithium-induced facilitation of neurogenesis and cognitive functions declines as brain Aβ deposition and pathology increases. CONCLUSIONS: Lithium, when given on time, stimulates neurogenesis and counteracts AD-like pathology.

  1. Large margin classification with indefinite similarities

    KAUST Repository

    Alabdulmohsin, Ibrahim

    2016-01-07

    Classification with indefinite similarities has attracted attention in the machine learning community. This is partly due to the fact that many similarity functions that arise in practice are not symmetric positive semidefinite, i.e. the Mercer condition is not satisfied, or the Mercer condition is difficult to verify. Examples of such indefinite similarities in machine learning applications are ample including, for instance, the BLAST similarity score between protein sequences, human-judged similarities between concepts and words, and the tangent distance or the shape matching distance in computer vision. Nevertheless, previous works on classification with indefinite similarities are not fully satisfactory. They have either introduced sources of inconsistency in handling past and future examples using kernel approximation, settled for local-minimum solutions using non-convex optimization, or produced non-sparse solutions by learning in Krein spaces. Despite the large volume of research devoted to this subject lately, we demonstrate in this paper how an old idea, namely the 1-norm support vector machine (SVM) proposed more than 15 years ago, has several advantages over more recent work. In particular, the 1-norm SVM method is conceptually simpler, which makes it easier to implement and maintain. It is competitive, if not superior to, all other methods in terms of predictive accuracy. Moreover, it produces solutions that are often sparser than more recent methods by several orders of magnitude. In addition, we provide various theoretical justifications by relating 1-norm SVM to well-established learning algorithms such as neural networks, SVM, and nearest neighbor classifiers. Finally, we conduct a thorough experimental evaluation, which reveals that the evidence in favor of 1-norm SVM is statistically significant.

  2. Similarity analysis between quantum images

    Science.gov (United States)

    Zhou, Ri-Gui; Liu, XingAo; Zhu, Changming; Wei, Lai; Zhang, Xiafen; Ian, Hou

    2018-06-01

    Similarity analyses between quantum images are so essential in quantum image processing that it provides fundamental research for the other fields, such as quantum image matching, quantum pattern recognition. In this paper, a quantum scheme based on a novel quantum image representation and quantum amplitude amplification algorithm is proposed. At the end of the paper, three examples and simulation experiments show that the measurement result must be 0 when two images are same, and the measurement result has high probability of being 1 when two images are different.

  3. Similarity flows in relativistic hydrodynamics

    International Nuclear Information System (INIS)

    Blaizot, J.P.; Ollitrault, J.Y.

    1986-01-01

    In ultra-relativistic heavy ion collisions, one expects in particular to observe a deconfinement transition leading to a formation of quark gluon plasma. In the framework of the hydrodynamic model, experimental signatures of such a plasma may be looked for as observable consequences of a first order transition on the evolution of the system. In most of the possible scenario, the phase transition is accompanied with discontinuities in the hydrodynamic flow, such as shock waves. The method presented in this paper has been developed to treat without too much numerical effort such discontinuous flow. It relies heavily on the use of similarity solutions of the hydrodynamic equations

  4. Similarity, trust in institutions, affect, and populism

    DEFF Research Database (Denmark)

    Scholderer, Joachim; Finucane, Melissa L.

    -based evaluations are fundamental to human information processing, they can contribute significantly to other judgments (such as the risk, cost-effectiveness, trustworthiness) of the same stimulus object. Although deliberation and analysis are certainly important in some decision-making circumstances, reliance...... on affect is a quicker, easier, and a more efficient way of navigating in a complex and uncertain world. Hence, many theorists give affect a direct and primary role in motivating behavior. Taken together, the results provide uncannily strong support for the value-similarity hypothesis, strengthening...... types of information about gene technology. The materials were attributed to different institutions. The results indicated that participants' trust in an institution was a function of the similarity between the position advocated in the materials and participants' own attitudes towards gene technology...

  5. Slower EEG alpha generation, synchronization and "flow"-possible biomarkers of cognitive impairment and neuropathology of minor stroke.

    Science.gov (United States)

    Petrovic, Jelena; Milosevic, Vuk; Zivkovic, Miroslava; Stojanov, Dragan; Milojkovic, Olga; Kalauzi, Aleksandar; Saponjic, Jasna

    2017-01-01

    We investigated EEG rhythms, particularly alpha activity, and their relationship to post-stroke neuropathology and cognitive functions in the subacute and chronic stages of minor strokes. We included 10 patients with right middle cerebral artery (MCA) ischemic strokes and 11 healthy controls. All the assessments of stroke patients were done both in the subacute and chronic stages. Neurological impairment was measured using the National Institute of Health Stroke Scale (NIHSS), whereas cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA) and MoCA memory index (MoCA-MIS). The EEG was recorded using a 19 channel EEG system with standard EEG electrode placement. In particular, we analyzed the EEGs derived from the four lateral frontal (F3, F7, F4, F8), and corresponding lateral posterior (P3, P4, T5, T6) electrodes. Quantitative EEG analysis included: the group FFT spectra, the weighted average of alpha frequency (αAVG), the group probability density distributions of all conventional EEG frequency band relative amplitudes (EEG microstructure), the inter- and intra-hemispheric coherences, and the topographic distribution of alpha carrier frequency phase potentials (PPs). Statistical analysis was done using a Kruskal-Wallis ANOVA with a post-hoc Mann-Whitney U two-tailed test, and Spearman's correlation. We demonstrated transient cognitive impairment alongside a slower alpha frequency ( α AVG) in the subacute right MCA stroke patients vs. the controls. This slower alpha frequency showed no amplitude change, but was highly synchronized intra-hemispherically, overlying the ipsi-lesional hemisphere, and inter-hemispherically, overlying the frontal cortex. In addition, the disturbances in EEG alpha activity in subacute stroke patients were expressed as a decrease in alpha PPs over the frontal cortex and an altered "alpha flow", indicating the sustained augmentation of inter-hemispheric interactions. Although the stroke induced slower alpha was a

  6. Slower EEG alpha generation, synchronization and “flow”—possible biomarkers of cognitive impairment and neuropathology of minor stroke

    Directory of Open Access Journals (Sweden)

    Jelena Petrovic

    2017-09-01

    Full Text Available Background We investigated EEG rhythms, particularly alpha activity, and their relationship to post-stroke neuropathology and cognitive functions in the subacute and chronic stages of minor strokes. Methods We included 10 patients with right middle cerebral artery (MCA ischemic strokes and 11 healthy controls. All the assessments of stroke patients were done both in the subacute and chronic stages. Neurological impairment was measured using the National Institute of Health Stroke Scale (NIHSS, whereas cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA and MoCA memory index (MoCA-MIS. The EEG was recorded using a 19 channel EEG system with standard EEG electrode placement. In particular, we analyzed the EEGs derived from the four lateral frontal (F3, F7, F4, F8, and corresponding lateral posterior (P3, P4, T5, T6 electrodes. Quantitative EEG analysis included: the group FFT spectra, the weighted average of alpha frequency (αAVG, the group probability density distributions of all conventional EEG frequency band relative amplitudes (EEG microstructure, the inter- and intra-hemispheric coherences, and the topographic distribution of alpha carrier frequency phase potentials (PPs. Statistical analysis was done using a Kruskal–Wallis ANOVA with a post-hoc Mann–Whitney U two-tailed test, and Spearman’s correlation. Results We demonstrated transient cognitive impairment alongside a slower alpha frequency (αAVG in the subacute right MCA stroke patients vs. the controls. This slower alpha frequency showed no amplitude change, but was highly synchronized intra-hemispherically, overlying the ipsi-lesional hemisphere, and inter-hemispherically, overlying the frontal cortex. In addition, the disturbances in EEG alpha activity in subacute stroke patients were expressed as a decrease in alpha PPs over the frontal cortex and an altered “alpha flow”, indicating the sustained augmentation of inter-hemispheric interactions

  7. Stochastic self-similar and fractal universe

    International Nuclear Information System (INIS)

    Iovane, G.; Laserra, E.; Tortoriello, F.S.

    2004-01-01

    The structures formation of the Universe appears as if it were a classically self-similar random process at all astrophysical scales. An agreement is demonstrated for the present hypotheses of segregation with a size of astrophysical structures by using a comparison between quantum quantities and astrophysical ones. We present the observed segregated Universe as the result of a fundamental self-similar law, which generalizes the Compton wavelength relation. It appears that the Universe has a memory of its quantum origin as suggested by R. Penrose with respect to quasi-crystal. A more accurate analysis shows that the present theory can be extended from the astrophysical to the nuclear scale by using generalized (stochastically) self-similar random process. This transition is connected to the relevant presence of the electromagnetic and nuclear interactions inside the matter. In this sense, the presented rule is correct from a subatomic scale to an astrophysical one. We discuss the near full agreement at organic cell scale and human scale too. Consequently the Universe, with its structures at all scales (atomic nucleus, organic cell, human, planet, solar system, galaxy, clusters of galaxy, super clusters of galaxy), could have a fundamental quantum reason. In conclusion, we analyze the spatial dimensions of the objects in the Universe as well as space-time dimensions. The result is that it seems we live in an El Naschie's E-infinity Cantorian space-time; so we must seriously start considering fractal geometry as the geometry of nature, a type of arena where the laws of physics appear at each scale in a self-similar way as advocated long ago by the Swedish school of astrophysics

  8. Contextual Factors for Finding Similar Experts

    DEFF Research Database (Denmark)

    Hofmann, Katja; Balog, Krisztian; Bogers, Toine

    2010-01-01

    -seeking models, are rarely taken into account. In this article, we extend content-based expert-finding approaches with contextual factors that have been found to influence human expert finding. We focus on a task of science communicators in a knowledge-intensive environment, the task of finding similar experts......, given an example expert. Our approach combines expertise-seeking and retrieval research. First, we conduct a user study to identify contextual factors that may play a role in the studied task and environment. Then, we design expert retrieval models to capture these factors. We combine these with content......-based retrieval models and evaluate them in a retrieval experiment. Our main finding is that while content-based features are the most important, human participants also take contextual factors into account, such as media experience and organizational structure. We develop two principled ways of modeling...

  9. Evaluation of Avulsion-Induced Neuropathology in Rat Spinal Cords with 18F-FDG Micro-PET/CT.

    Directory of Open Access Journals (Sweden)

    Ze-Min Ling

    Full Text Available Brachial plexus root avulsion (BPRA leads to dramatic motoneuron death and glial reactions in the corresponding spinal segments at the late stage of injury. To protect spinal motoneurons, assessment of the affected spinal segments should be done at an earlier stage of the injury. In this study, we employed 18F-FDG small-animal PET/CT to assess the severity of BPRA-induced cervical spinal cord injuries. Adult Sprague-Dawley rats were randomly treated and divided into three groups: Av+NS (brachial plexus root avulsion (Av treated with normal saline, Av+GM1 (treated with monosialoganglioside, and control. At time points of 3 day (d, 1 week (w, 2 w, 4 w and 8 w post-injury, 18F-FDG micro-PET/CT scans and neuropathology assessments of the injured spinal roots, as well as the spinal cord, were performed. The outcomes of the different treatments were compared. The results showed that BPRA induced local bleeding and typical Wallerian degeneration of the avulsed roots accompanied by 18F-FDG accumulations at the ipsilateral cervical intervertebral foramen. BPRA-induced astrocyte reactions and overexpression of neuronal nitric oxide synthase in the motoneurons correlated with higher 18F-FDG uptake in the ipsilateral cervical spinal cord during the first 2 w post-injury. The GM1 treatment reduced BPRA-induced astrocyte reactions and inhibited the de novo nNOS expressions in spinal motoneurons. The GM1 treatment also protected spinal motoneurons from avulsion within the first 4 w post-injury. The data from this study suggest that 18F-FDG PET/CT could be used to assess the severity of BPRA-induced primary and secondary injuries in the spinal cord. Furthermore, GM1 is an effective drug for reducing primary and secondary spinal cord injuries following BPRA.

  10. Self-similar gravitational clustering

    International Nuclear Information System (INIS)

    Efstathiou, G.; Fall, S.M.; Hogan, C.

    1979-01-01

    The evolution of gravitational clustering is considered and several new scaling relations are derived for the multiplicity function. These include generalizations of the Press-Schechter theory to different densities and cosmological parameters. The theory is then tested against multiplicity function and correlation function estimates for a series of 1000-body experiments. The results are consistent with the theory and show some dependence on initial conditions and cosmological density parameter. The statistical significance of the results, however, is fairly low because of several small number effects in the experiments. There is no evidence for a non-linear bootstrap effect or a dependence of the multiplicity function on the internal dynamics of condensed groups. Empirical estimates of the multiplicity function by Gott and Turner have a feature near the characteristic luminosity predicted by the theory. The scaling relations allow the inference from estimates of the galaxy luminosity function that galaxies must have suffered considerable dissipation if they originally formed from a self-similar hierarchy. A method is also developed for relating the multiplicity function to similar measures of clustering, such as those of Bhavsar, for the distribution of galaxies on the sky. These are shown to depend on the luminosity function in a complicated way. (author)

  11. Genomic and expression analyses of Tursiops truncatus T cell receptor gamma (TRG) and alpha/delta (TRA/TRD) loci reveal a similar basic public γδ repertoire in dolphin and human.

    Science.gov (United States)

    Linguiti, Giovanna; Antonacci, Rachele; Tasco, Gianluca; Grande, Francesco; Casadio, Rita; Massari, Serafina; Castelli, Vito; Consiglio, Arianna; Lefranc, Marie-Paule; Ciccarese, Salvatrice

    2016-08-15

    The bottlenose dolphin (Tursiops truncatus) is a mammal that belongs to the Cetartiodactyla and have lived in marine ecosystems for nearly 60 millions years. Despite its popularity, our knowledge about its adaptive immunity and evolution is very limited. Furthermore, nothing is known about the genomics and evolution of dolphin antigen receptor immunity. Here we report a evolutionary and expression study of Tursiops truncatus T cell receptor gamma (TRG) and alpha/delta (TRA/TRD) genes. We have identified in silico the TRG and TRA/TRD genes and analyzed the relevant mature transcripts in blood and in skin from four subjects. The dolphin TRG locus is the smallest and simplest of all mammalian loci as yet studied. It shows a genomic organization comprising two variable (V1 and V2), three joining (J1, J2 and J3) and a single constant (C), genes. Despite the fragmented nature of the genome assemblies, we deduced the TRA/TRD locus organization, with the recent TRDV1 subgroup genes duplications, as it is expected in artiodactyls. Expression analysis from blood of a subject allowed us to assign unambiguously eight TRAV genes to those annotated in the genomic sequence and to twelve new genes, belonging to five different subgroups. All transcripts were productive and no relevant biases towards TRAV-J rearrangements are observed. Blood and skin from four unrelated subjects expression data provide evidence for an unusual ratio of productive/unproductive transcripts which arise from the TRG V-J gene rearrangement and for a "public" gamma delta TR repertoire. The productive cDNA sequences, shared both in the same and in different individuals, include biases of the TRGV1 and TRGJ2 genes. The high frequency of TRGV1-J2/TRDV1- D1-J4 productive rearrangements in dolphins may represent an interesting oligo-clonal population comparable to that found in human with the TRGV9- JP/TRDV2-D-J T cells and in primates. Although the features of the TRG and TRA/TRD loci organization reflect

  12. Seniority bosons from similarity transformations

    International Nuclear Information System (INIS)

    Geyer, H.B.

    1986-01-01

    The requirement of associating in the boson space seniority with twice the number of non-s bosons defines a similarity transformation which re-expresses the Dyson pair boson images in terms of seniority bosons. In particular the fermion S-pair creation operator is mapped onto an operator which, unlike the pair boson image, does not change the number of non-s bosons. The original results of Otsuka, Arima and Iachello are recovered by this procedure while at the same time they are generalized to include g-bosons or even bosons with J>4 as well as any higher order boson terms. Furthermore the seniority boson images are valid for an arbitrary number of d- or g-bosons - a result which is not readily obtainable within the framework of the usual Marumori- or OAI-method

  13. Supplementation with a recombinant human chorionic gonadotropin microdose leads to similar outcomes in ovarian stimulation with recombinant follicle-stimulating hormone using either a gonadotropin-releasing hormone agonist or antagonist for pituitary suppression.

    Science.gov (United States)

    Cavagna, Mario; Maldonado, Luiz Guilherme Louzada; de Souza Bonetti, Tatiana Carvalho; de Almeida Ferreira Braga, Daniela Paes; Iaconelli, Assumpto; Borges, Edson

    2010-06-01

    To compare the outcomes of protocols for ovarian stimulation with recombinant hCG microdose, with GnRH agonists and antagonists for pituitary suppression. Prospective nonrandomized clinical trial. A private assisted reproduction center. We studied 182 patients undergoing intracytoplasmic sperm injection (ICSI) cycles, allocated into two groups: GnRH agonist group, in which patients received a GnRH agonist (n = 73), and a GnRH antagonist group, in which patients were administered a GnRH antagonist for pituitary suppression (n = 109). Pituitary suppression with GnRH agonist or GnRH antagonist. Ovarian stimulation carried out with recombinant FSH and supplemented with recombinant hCG microdose. Total dose of recombinant FSH and recombinant hCG administered; E(2) concentrations and endometrial width on the day of hCG trigger; number of follicles aspirated, oocytes and mature oocytes retrieved; fertilization, pregnancy (PR), implantation, and miscarriage rates. The total dose of recombinant FSH and recombinant hCG administered were similar between groups, as were the E(2) concentrations and endometrial width. The number of follicles aspirated, oocytes, and metaphase II oocytes collected were also comparable. There were no statistically significant differences in fertilization, PR, implantation, and miscarriage rates in the GnRH agonist and GnRH antagonist groups. When using recombinant hCG microdose supplementation for controlled ovarian stimulation (COS), there are no differences in laboratory or clinical outcomes with the use of either GnRH antagonist or agonist for pituitary suppression. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  14. Canine degenerative myelopathy: a model of human amyotrophic lateral sclerosis.

    Science.gov (United States)

    Nardone, Raffaele; Höller, Yvonne; Taylor, Alexandra C; Lochner, Piergiorgio; Tezzon, Frediano; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen

    2016-02-01

    Canine degenerative myelopathy (CDM) represents a unique naturally occurring animal model for human amyotrophic lateral sclerosis (ALS) because of similar clinical signs, neuropathologic findings, and involvement of the superoxide dismutase 1 (SOD1) mutation. A definitive diagnosis can only be made postmortem through microscopic detection of axonal degeneration, demyelination and astroglial proliferation, which is more severe in the dorsal columns of the thoracic spinal cord and in the dorsal portion of the lateral funiculus. Interestingly, the muscle acetylcholine receptor complexes are intact in CDM prior to functional impairment, thus suggesting that muscle atrophy in CDM does not result from physical denervation. Moreover, since sensory involvement seems to play an important role in CDM progression, a more careful investigation of the sensory pathology in ALS is also warranted. The importance of SOD1 expression remains unclear, while oxidative stress and denatured ubiquinated proteins appear to play a crucial role in the pathogenesis of CDM. In this updated narrative review we performed a systematic search of the published studies on CDM that may shed light on the pathophysiological mechanisms of human ALS. A better understanding of the factors that determine the disease progression in CDM may be beneficial for the development of effective treatments for ALS. Copyright © 2015 Elsevier GmbH. All rights reserved.

  15. Alaska, Gulf spills share similarities

    International Nuclear Information System (INIS)

    Usher, D.

    1991-01-01

    The accidental Exxon Valdez oil spill in Alaska and the deliberate dumping of crude oil into the Persian Gulf as a tactic of war contain both glaring differences and surprising similarities. Public reaction and public response was much greater to the Exxon Valdez spill in pristine Prince William Sound than to the war-related tragedy in the Persian Gulf. More than 12,000 workers helped in the Alaskan cleanup; only 350 have been involved in Kuwait. But in both instances, environmental damages appear to be less than anticipated. Natures highly effective self-cleansing action is primarily responsible for minimizing the damages. One positive action growing out of the two incidents is increased international cooperation and participation in oil-spill clean-up efforts. In 1990, in the aftermath of the Exxon Valdez spill, 94 nations signed an international accord on cooperation in future spills. The spills can be historic environmental landmarks leading to creation of more sophisticated response systems worldwide

  16. Semantic Similarity between Web Documents Using Ontology

    Science.gov (United States)

    Chahal, Poonam; Singh Tomer, Manjeet; Kumar, Suresh

    2018-06-01

    The World Wide Web is the source of information available in the structure of interlinked web pages. However, the procedure of extracting significant information with the assistance of search engine is incredibly critical. This is for the reason that web information is written mainly by using natural language, and further available to individual human. Several efforts have been made in semantic similarity computation between documents using words, concepts and concepts relationship but still the outcome available are not as per the user requirements. This paper proposes a novel technique for computation of semantic similarity between documents that not only takes concepts available in documents but also relationships that are available between the concepts. In our approach documents are being processed by making ontology of the documents using base ontology and a dictionary containing concepts records. Each such record is made up of the probable words which represents a given concept. Finally, document ontology's are compared to find their semantic similarity by taking the relationships among concepts. Relevant concepts and relations between the concepts have been explored by capturing author and user intention. The proposed semantic analysis technique provides improved results as compared to the existing techniques.

  17. Semantic Similarity between Web Documents Using Ontology

    Science.gov (United States)

    Chahal, Poonam; Singh Tomer, Manjeet; Kumar, Suresh

    2018-03-01

    The World Wide Web is the source of information available in the structure of interlinked web pages. However, the procedure of extracting significant information with the assistance of search engine is incredibly critical. This is for the reason that web information is written mainly by using natural language, and further available to individual human. Several efforts have been made in semantic similarity computation between documents using words, concepts and concepts relationship but still the outcome available are not as per the user requirements. This paper proposes a novel technique for computation of semantic similarity between documents that not only takes concepts available in documents but also relationships that are available between the concepts. In our approach documents are being processed by making ontology of the documents using base ontology and a dictionary containing concepts records. Each such record is made up of the probable words which represents a given concept. Finally, document ontology's are compared to find their semantic similarity by taking the relationships among concepts. Relevant concepts and relations between the concepts have been explored by capturing author and user intention. The proposed semantic analysis technique provides improved results as compared to the existing techniques.

  18. TREM2 Overexpression has No Improvement on Neuropathology and Cognitive Impairment in Aging APPswe/PS1dE9 Mice.

    Science.gov (United States)

    Jiang, Teng; Wan, Yu; Zhang, Ying-Dong; Zhou, Jun-Shan; Gao, Qing; Zhu, Xi-Chen; Shi, Jian-Quan; Lu, Huan; Tan, Lan; Yu, Jin-Tai

    2017-03-01

    Previously, we showed that overexpression of triggering receptor expressed on myeloid cells 2 (TREM2), a microglia-specific immune receptor, in the brain of a middle-aged (7 months old) APPswe/PS1dE9 mice could ameliorate Alzheimer's disease (AD)-related neuropathology by enhancement of microglial amyloid-β (Aβ) phagocytosis. Since AD is an age-related neurodegenerative disorder, it is critical to assess the efficacy of TREM2 overexpression in aging animals with an advanced disease stage. In vivo, we employed a lentiviral strategy to overexpress TREM2 in the brain of aging (18 months old) APPswe/PS1dE9 mice, and observed its efficacy on AD-related neuropathology and cognitive functions. Afterwards, we directly isolated microglia from middle-aged and aging APPswe/PS1dE9 mice and determined effects of TREM2 overexpression on microglial Aβ phagocytosis and Aβ-binding receptors expression in vitro. In aging APPswe/PS1dE9 mice, TREM2 overexpression has no beneficial effect on AD-related neuropathology and spatial cognitive functions. Of note, in vitro experiments showed a significant reduction of Aβ phagocytosis in microglia from aging APPswe/PS1dE9 mice, possibly attributing to the declined expression of Aβ-binding receptors. Meanwhile, this phagocytic deficit in microglia from aging APPswe/PS1dE9 mice cannot be rescued by TREM2 overexpression. Taken together, our study shows that TREM2 overexpression fails to provide neuroprotection in aging APPswe/PS1dE9 mice, possibly attributing to deficits in microglial Aβ phagocytosis at the late-stage of disease progression. These findings indicate that TREM2-mediated protection in AD is at least partially dependent on the reservation of microglial phagocytic functions, emphasizing the importance of early therapeutic interventions for this devastating disease.

  19. Pedigree with frontotemporal lobar degeneration – motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9

    Directory of Open Access Journals (Sweden)

    Loy Clement T

    2008-08-01

    Full Text Available Abstract Background Frontotemporal lobar degeneration (FTLD represents a clinically, pathologically and genetically heterogenous neurodegenerative disorder, often complicated by neurological signs such as motor neuron-related limb weakness, spasticity and paralysis, parkinsonism and gait disturbances. Linkage to chromosome 9p had been reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD and motor neuron disease (MND. The objective in this study is to identify the genetic locus in a multi-generational Australian family with FTLD-MND. Methods Clinical review and standard neuropathological analysis of brain sections from affected pedigree members. Genome-wide scan using microsatellite markers and single nucleotide polymorphism fine mapping. Examination of candidate genes by direct DNA sequencing. Results Neuropathological examination revealed cytoplasmic deposition of the TDP-43 protein in three affected individuals. Moreover, we identify a family member with clinical Alzheimer's disease, and FTLD-Ubiquitin neuropathology. Genetic linkage and haplotype analyses, defined a critical region between markers D9S169 and D9S1845 on chromosome 9p21. Screening of all candidate genes within this region did not reveal any novel genetic alterations that co-segregate with disease haplotype, suggesting that one individual carrying a meiotic recombination may represent a phenocopy. Re-analysis of linkage data using the new affection status revealed a maximal two-point LOD score of 3.24 and a multipoint LOD score of 3.41 at marker D9S1817. This provides the highest reported LOD scores from a single FTLD-MND pedigree. Conclusion Our reported increase in the minimal disease region should inform other researchers that the chromosome 9 locus may be more telomeric than predicted by published recombination boundaries. Moreover, the existence of a family member with clinical Alzheimer's disease, and who shares the disease

  20. Neuropathology of Autism

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-07-01

    Full Text Available A computerized imaging program was used to measure cell column morphological features in area 9 of the prefrontal cortex and areas 21 and posterior 22 in the temporal lobe of 9 brains of autistic patients and controls, in a study at the Medical College of Georgia, Augusta.

  1. Neuropathology of stress

    NARCIS (Netherlands)

    Lucassen, P.J.; Pruessner, J.; Sousa, N.; Almeida, O.F.X.; van Dam, A.M.; Rajkowska, G.; Swaab, D.F.; Czéh, B.

    2014-01-01

    Environmental challenges are part of daily life for any individual. In fact, stress appears to be increasingly present in our modern, and demanding, industrialized society. Virtually every aspect of our body and brain can be influenced by stress and although its effects are partly mediated by

  2. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection

    Directory of Open Access Journals (Sweden)

    Erica L. McGrath

    2017-03-01

    Full Text Available Zika virus (ZIKV infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7, to infect primary human neural stem cells (hNSCs originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection.

  3. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection.

    Science.gov (United States)

    McGrath, Erica L; Rossi, Shannan L; Gao, Junling; Widen, Steven G; Grant, Auston C; Dunn, Tiffany J; Azar, Sasha R; Roundy, Christopher M; Xiong, Ying; Prusak, Deborah J; Loucas, Bradford D; Wood, Thomas G; Yu, Yongjia; Fernández-Salas, Ildefonso; Weaver, Scott C; Vasilakis, Nikos; Wu, Ping

    2017-03-14

    Zika virus (ZIKV) infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7), to infect primary human neural stem cells (hNSCs) originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. International recommendation for a comprehensive neuropathologic workup of epilepsy surgery brain tissue: A consensus Task Force report from the ILAE Commission on Diagnostic Methods.

    Science.gov (United States)

    Blümcke, Ingmar; Aronica, Eleonora; Miyata, Hajime; Sarnat, Harvey B; Thom, Maria; Roessler, Karl; Rydenhag, Bertil; Jehi, Lara; Krsek, Pavel; Wiebe, Samuel; Spreafico, Roberto

    2016-03-01

    Epilepsy surgery is an effective treatment in many patients with drug-resistant focal epilepsies. An early decision for surgical therapy is facilitated by a magnetic resonance imaging (MRI)-visible brain lesion congruent with the electrophysiologically abnormal brain region. Recent advances in the pathologic diagnosis and classification of epileptogenic brain lesions are helpful for clinical correlation, outcome stratification, and patient management. However, application of international consensus classification systems to common epileptic pathologies (e.g., focal cortical dysplasia [FCD] and hippocampal sclerosis [HS]) necessitates standardized protocols for neuropathologic workup of epilepsy surgery specimens. To this end, the Task Force of Neuropathology from the International League Against Epilepsy (ILAE) Commission on Diagnostic Methods developed a consensus standard operational procedure for tissue inspection, distribution, and processing. The aims are to provide a systematic framework for histopathologic workup, meeting minimal standards and maximizing current and future opportunities for morphofunctional correlations and molecular studies for both clinical care and research. Whenever feasible, anatomically intact surgical specimens are desirable to enable systematic analysis in selective hippocampectomies, temporal lobe resections, and lesional or nonlesional neocortical samples. Correct orientation of sample and the sample's relation to neurophysiologically aberrant sites requires good communication between pathology and neurosurgical teams. Systematic tissue sampling of 5-mm slabs along a defined anatomic axis and application of a limited immunohistochemical panel will ensure a reliable differential diagnosis of main pathologies encountered in epilepsy surgery. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  5. Congenital Hypothalamic "Hamartoblastoma" Versus "Hamartoma": Suggestions for Neuropathologic Terminology Emanating From a Mid-gestational Autopsy Case of Pallister-Hall Syndrome.

    Science.gov (United States)

    Dunham, C; McFadden, D; Dahlgren, L; Butler, B; Hamilton, S; McKinnon, M

    2018-01-01

    Pallister-Hall syndrome (PHS) is a rare malformative disorder that is due to truncating functional repressor mutations in GLI3. Since the seminal publication in 1980, hypothalamic tumors have been recognized to be a cardinal feature of PHS. In their original description of the neuropathologic features of PHS, Clarren et al. coined the term "hamartoblastoma" to characterize what they deemed to be a dual malformative and neoplastic mass of the hypothalamus. In subsequent published cases/series of PHS, the term "hamartoma" was often substituted for hamartoblastoma given what appeared to be a benign natural history of this lesion. Additional confusion in the literature has ensued since most hypothalamic hamartomas (HH) encountered on the clinical neuropathology service are "isolated" in nature (ie, no other congenital malformations) and present in a very different and stereotypical fashion with gelastic seizures and/or precocious puberty. While genomic investigations of isolated HH have begun to uncover a mutational profile of these cases, GLI3 mutations have only been recognized in a small subset of isolated HH. Herein, we describe the autopsy findings from a 21-week gestational age fetus with features of PHS. Moreover, we provide a detailed description of the hypothalamic tumor affecting this fetus and propose a novel subclassification of HH, distinguishing syndromic from isolated forms based upon the presence or absence of neocortical-like areas.

  6. Formulation of a medical food cocktail for Alzheimer's disease: beneficial effects on cognition and neuropathology in a mouse model of the disease.

    Directory of Open Access Journals (Sweden)

    Anna Parachikova

    2010-11-01

    Full Text Available Dietary supplements have been extensively studied for their beneficial effects on cognition and AD neuropathology. The current study examines the effect of a medical food cocktail consisting of the dietary supplements curcumin, piperine, epigallocatechin gallate, α-lipoic acid, N-acetylcysteine, B vitamins, vitamin C, and folate on cognitive functioning and the AD hallmark features and amyloid-beta (Aβ in the Tg2576 mouse model of the disease.The study found that administering the medical food cocktail for 6 months improved cortical- and hippocampal- dependent learning in the transgenic mice, rendering their performance indistinguishable from non-transgenic controls. Coinciding with this improvement in learning and memory, we found that treatment resulted in decreased soluble Aβ, including Aβ oligomers, previously found to be linked to cognitive functioning.In conclusion, the current study demonstrates that combination diet consisting of natural dietary supplements improves cognitive functioning while decreasing AD neuropathology and may thus represent a safe, natural treatment for AD.

  7. FRESCO: Referential compression of highly similar sequences.

    Science.gov (United States)

    Wandelt, Sebastian; Leser, Ulf

    2013-01-01

    In many applications, sets of similar texts or sequences are of high importance. Prominent examples are revision histories of documents or genomic sequences. Modern high-throughput sequencing technologies are able to generate DNA sequences at an ever-increasing rate. In parallel to the decreasing experimental time and cost necessary to produce DNA sequences, computational requirements for analysis and storage of the sequences are steeply increasing. Compression is a key technology to deal with this challenge. Recently, referential compression schemes, storing only the differences between a to-be-compressed input and a known reference sequence, gained a lot of interest in this field. In this paper, we propose a general open-source framework to compress large amounts of biological sequence data called Framework for REferential Sequence COmpression (FRESCO). Our basic compression algorithm is shown to be one to two orders of magnitudes faster than comparable related work, while achieving similar compression ratios. We also propose several techniques to further increase compression ratios, while still retaining the advantage in speed: 1) selecting a good reference sequence; and 2) rewriting a reference sequence to allow for better compression. In addition,we propose a new way of further boosting the compression ratios by applying referential compression to already referentially compressed files (second-order compression). This technique allows for compression ratios way beyond state of the art, for instance,4,000:1 and higher for human genomes. We evaluate our algorithms on a large data set from three different species (more than 1,000 genomes, more than 3 TB) and on a collection of versions of Wikipedia pages. Our results show that real-time compression of highly similar sequences at high compression ratios is possible on modern hardware.

  8. Development of similarity theory for control systems

    Science.gov (United States)

    Myshlyaev, L. P.; Evtushenko, V. F.; Ivushkin, K. A.; Makarov, G. V.

    2018-05-01

    The area of effective application of the traditional similarity theory and the need necessity of its development for systems are discussed. The main statements underlying the similarity theory of control systems are given. The conditions for the similarity of control systems and the need for similarity control control are formulated. Methods and algorithms for estimating and similarity control of control systems and the results of research of control systems based on their similarity are presented. The similarity control of systems includes the current evaluation of the degree of similarity of control systems and the development of actions controlling similarity, and the corresponding targeted change in the state of any element of control systems.

  9. Marriage Matters: Spousal Similarity in Life Satisfaction

    OpenAIRE

    Ulrich Schimmack; Richard Lucas

    2006-01-01

    Examined the concurrent and cross-lagged spousal similarity in life satisfaction over a 21-year period. Analyses were based on married couples (N = 847) in the German Socio-Economic Panel (SOEP). Concurrent spousal similarity was considerably higher than one-year retest similarity, revealing spousal similarity in the variable component of life satisfac-tion. Spousal similarity systematically decreased with length of retest interval, revealing simi-larity in the changing component of life sati...

  10. Prioritization of candidate disease genes by combining topological similarity and semantic similarity.

    Science.gov (United States)

    Liu, Bin; Jin, Min; Zeng, Pan

    2015-10-01

    The identification of gene-phenotype relationships is very important for the treatment of human diseases. Studies have shown that genes causing the same or similar phenotypes tend to interact with each other in a protein-protein interaction (PPI) network. Thus, many identification methods based on the PPI network model have achieved good results. However, in the PPI network, some interactions between the proteins encoded by candidate gene and the proteins encoded by known disease genes are very weak. Therefore, some studies have combined the PPI network with other genomic information and reported good predictive performances. However, we believe that the results could be further improved. In this paper, we propose a new method that uses the semantic similarity between the candidate gene and known disease genes to set the initial probability vector of a random walk with a restart algorithm in a human PPI network. The effectiveness of our method was demonstrated by leave-one-out cross-validation, and the experimental results indicated that our method outperformed other methods. Additionally, our method can predict new causative genes of multifactor diseases, including Parkinson's disease, breast cancer and obesity. The top predictions were good and consistent with the findings in the literature, which further illustrates the effectiveness of our method. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. On different forms of self similarity

    International Nuclear Information System (INIS)

    Aswathy, R.K.; Mathew, Sunil

    2016-01-01

    Fractal geometry is mainly based on the idea of self-similar forms. To be self-similar, a shape must able to be divided into parts that are smaller copies, which are more or less similar to the whole. There are different forms of self similarity in nature and mathematics. In this paper, some of the topological properties of super self similar sets are discussed. It is proved that in a complete metric space with two or more elements, the set of all non super self similar sets are dense in the set of all non-empty compact sub sets. It is also proved that the product of self similar sets are super self similar in product metric spaces and that the super self similarity is preserved under isometry. A characterization of super self similar sets using contracting sub self similarity is also presented. Some relevant counterexamples are provided. The concepts of exact super and sub self similarity are introduced and a necessary and sufficient condition for a set to be exact super self similar in terms of condensation iterated function systems (Condensation IFS’s) is obtained. A method to generate exact sub self similar sets using condensation IFS’s and the denseness of exact super self similar sets are also discussed.

  12. State and Mafia, Differences and Similarities

    Directory of Open Access Journals (Sweden)

    Alfano Vincenzo

    2015-02-01

    Full Text Available The purpose of this article is to investigate about the differences and, if any, the similarities among the modern State and the mafia criminal organizations. In particular, starting from their definitions, I will try to find the differences between State and mafia, to then focus on the operational aspects of the functioning of these two organizations, with specific reference to the effect/impact that both these human constructs have on citizens’ existences, and especially on citizen’s economic lives. All this in order to understand whether it is possible to identify an objective difference – beside morals – between taxation by the modern State and extortion by criminal organizations. With this of course I do not want to argue that the mafia is in any way justifiable or absolvable, nor that it is better than the State. However, I want to investigate whether there is a real, logical reason why the State should be considered by the citizens more desirable than the criminal organizations oppressing Southern Italy, from a strictly logical point of view and not from the point of view of ethics and morality.

  13. [Lower urinary tract dysfunction and neuropathological findings of the neural circuits controlling micturition in familial amyotrophic lateral sclerosis with L106V mutation in the SOD1 gene].

    Science.gov (United States)

    Hineno, Akiyo; Oyanagi, Kiyomitsu; Nakamura, Akinori; Shimojima, Yoshio; Yoshida, Kunihiro; Ikeda, Shu-Ichi

    2016-01-01

    We report lower urinary tract dysfunction and neuropathological findings of the neural circuits controlling micturition in the patients with familial amyotrophic lateral sclerosis having L106V mutation in the SOD1 gene. Ten of 20 patients showed lower urinary tract dysfunction and 5 patients developed within 1 year after the onset of weakness. In 8 patients with an artificial respirator, 6 patients showed lower urinary tract dysfunction. Lower urinary tract dysfunction and respiratory failure requiring an artificial respirator occurred simultaneously in 3 patients. Neuronal loss and gliosis were observed in the neural circuits controlling micturition, such as frontal lobe, thalamus, hypothalamus, striatum, periaqueductal gray, ascending spinal tract, lateral corticospinal tract, intermediolateral nucleus and Onufrowicz' nucleus. Lower urinary tract dysfunction, especially storage symptoms, developed about 1 year after the onset of weakness, and the dysfunction occurred simultaneously with artificial respirator use in the patients.

  14. Semantic similarity from natural language and ontology analysis

    CERN Document Server

    Harispe, Sébastien; Janaqi, Stefan

    2015-01-01

    Artificial Intelligence federates numerous scientific fields in the aim of developing machines able to assist human operators performing complex treatments---most of which demand high cognitive skills (e.g. learning or decision processes). Central to this quest is to give machines the ability to estimate the likeness or similarity between things in the way human beings estimate the similarity between stimuli.In this context, this book focuses on semantic measures: approaches designed for comparing semantic entities such as units of language, e.g. words, sentences, or concepts and instances def

  15. An electrophysiological signature of summed similarity in visual working memory.

    Science.gov (United States)

    van Vugt, Marieke K; Sekuler, Robert; Wilson, Hugh R; Kahana, Michael J

    2013-05-01

    Summed-similarity models of short-term item recognition posit that participants base their judgments of an item's prior occurrence on that item's summed similarity to the ensemble of items on the remembered list. We examined the neural predictions of these models in 3 short-term recognition memory experiments using electrocorticographic/depth electrode recordings and scalp electroencephalography. On each experimental trial, participants judged whether a test face had been among a small set of recently studied faces. Consistent with summed-similarity theory, participants' tendency to endorse a test item increased as a function of its summed similarity to the items on the just-studied list. To characterize this behavioral effect of summed similarity, we successfully fit a summed-similarity model to individual participant data from each experiment. Using the parameters determined from fitting the summed-similarity model to the behavioral data, we examined the relation between summed similarity and brain activity. We found that 4-9 Hz theta activity in the medial temporal lobe and 2-4 Hz delta activity recorded from frontal and parietal cortices increased with summed similarity. These findings demonstrate direct neural correlates of the similarity computations that form the foundation of several major cognitive theories of human recognition memory. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  16. Natural texture retrieval based on perceptual similarity measurement

    Science.gov (United States)

    Gao, Ying; Dong, Junyu; Lou, Jianwen; Qi, Lin; Liu, Jun

    2018-04-01

    A typical texture retrieval system performs feature comparison and might not be able to make human-like judgments of image similarity. Meanwhile, it is commonly known that perceptual texture similarity is difficult to be described by traditional image features. In this paper, we propose a new texture retrieval scheme based on texture perceptual similarity. The key of the proposed scheme is that prediction of perceptual similarity is performed by learning a non-linear mapping from image features space to perceptual texture space by using Random Forest. We test the method on natural texture dataset and apply it on a new wallpapers dataset. Experimental results demonstrate that the proposed texture retrieval scheme with perceptual similarity improves the retrieval performance over traditional image features.

  17. Large margin classification with indefinite similarities

    KAUST Repository

    Alabdulmohsin, Ibrahim; Cisse, Moustapha; Gao, Xin; Zhang, Xiangliang

    2016-01-01

    Classification with indefinite similarities has attracted attention in the machine learning community. This is partly due to the fact that many similarity functions that arise in practice are not symmetric positive semidefinite, i.e. the Mercer

  18. Testing Self-Similarity Through Lamperti Transformations

    KAUST Repository

    Lee, Myoungji; Genton, Marc G.; Jun, Mikyoung

    2016-01-01

    extensively, while statistical tests for self-similarity are scarce and limited to processes indexed in one dimension. This paper proposes a statistical hypothesis test procedure for self-similarity of a stochastic process indexed in one dimension and multi

  19. Personality similarity and life satisfaction in couples

    OpenAIRE

    Furler Katrin; Gomez Veronica; Grob Alexander

    2013-01-01

    The present study examined the association between personality similarity and life satisfaction in a large nationally representative sample of 1608 romantic couples. Similarity effects were computed for the Big Five personality traits as well as for personality profiles with global and differentiated indices of similarity. Results showed substantial actor and partner effects indicating that both partners' personality traits were related to both partners' life satisfaction. Personality similar...

  20. Testing Self-Similarity Through Lamperti Transformations

    KAUST Repository

    Lee, Myoungji

    2016-07-14

    Self-similar processes have been widely used in modeling real-world phenomena occurring in environmetrics, network traffic, image processing, and stock pricing, to name but a few. The estimation of the degree of self-similarity has been studied extensively, while statistical tests for self-similarity are scarce and limited to processes indexed in one dimension. This paper proposes a statistical hypothesis test procedure for self-similarity of a stochastic process indexed in one dimension and multi-self-similarity for a random field indexed in higher dimensions. If self-similarity is not rejected, our test provides a set of estimated self-similarity indexes. The key is to test stationarity of the inverse Lamperti transformations of the process. The inverse Lamperti transformation of a self-similar process is a strongly stationary process, revealing a theoretical connection between the two processes. To demonstrate the capability of our test, we test self-similarity of fractional Brownian motions and sheets, their time deformations and mixtures with Gaussian white noise, and the generalized Cauchy family. We also apply the self-similarity test to real data: annual minimum water levels of the Nile River, network traffic records, and surface heights of food wrappings. © 2016, International Biometric Society.

  1. Cognitive Profiles on the Severe Impairment Battery Are Similar in Alzheimer Disease and Down Syndrome With Dementia.

    Science.gov (United States)

    Dick, Malcolm B; Doran, Eric; Phelan, Michael; Lott, Ira T

    2016-01-01

    Previous research has revealed similarities in the neuropathology, clinical presentation, and risk factors between persons with Alzheimer disease from the general population (GP-AD) and those with Down syndrome (DS-AD). Less is known, however, about the extent of similarities and differences in the cognitive profiles of these 2 populations. Fifty-one moderate to severely demented GP-AD and 59 DS-AD individuals participated in this study which compared the cognitive profiles of these 2 populations on the Severe Impairment Battery (SIB), controlling for sex as well as level of functional ability using a modified version of the Bristol Activities of Daily Living Scale. Overall, the neuropsychological profiles of the higher-functioning individuals within the DS-AD and advanced GP-AD groups, as represented by mean difference scores on the SIB as a whole and across the 9 separate cognitive domains, were very similar to one another after adjusting for sex and functional impairment. To our knowledge, this is the first study to directly compare the cognitive profiles of these 2 populations on the SIB. Findings suggest that the underlying dementia in GP-AD and DS-AD may have corresponding and parallel effects on cognition.

  2. Notions of similarity for systems biology models.

    Science.gov (United States)

    Henkel, Ron; Hoehndorf, Robert; Kacprowski, Tim; Knüpfer, Christian; Liebermeister, Wolfram; Waltemath, Dagmar

    2018-01-01

    Systems biology models are rapidly increasing in complexity, size and numbers. When building large models, researchers rely on software tools for the retrieval, comparison, combination and merging of models, as well as for version control. These tools need to be able to quantify the differences and similarities between computational models. However, depending on the specific application, the notion of 'similarity' may greatly vary. A general notion of model similarity, applicable to various types of models, is still missing. Here we survey existing methods for the comparison of models, introduce quantitative measures for model similarity, and discuss potential applications of combined similarity measures. To frame model comparison as a general problem, we describe a theoretical approach to defining and computing similarities based on a combination of different model aspects. The six aspects that we define as potentially relevant for similarity are underlying encoding, references to biological entities, quantitative behaviour, qualitative behaviour, mathematical equations and parameters and network structure. We argue that future similarity measures will benefit from combining these model aspects in flexible, problem-specific ways to mimic users' intuition about model similarity, and to support complex model searches in databases. © The Author 2016. Published by Oxford University Press.

  3. Similar speaker recognition using nonlinear analysis

    International Nuclear Information System (INIS)

    Seo, J.P.; Kim, M.S.; Baek, I.C.; Kwon, Y.H.; Lee, K.S.; Chang, S.W.; Yang, S.I.

    2004-01-01

    Speech features of the conventional speaker identification system, are usually obtained by linear methods in spectral space. However, these methods have the drawback that speakers with similar voices cannot be distinguished, because the characteristics of their voices are also similar in spectral space. To overcome the difficulty in linear methods, we propose to use the correlation exponent in the nonlinear space as a new feature vector for speaker identification among persons with similar voices. We show that our proposed method surprisingly reduces the error rate of speaker identification system to speakers with similar voices

  4. On self-similar Tolman models

    International Nuclear Information System (INIS)

    Maharaj, S.D.

    1988-01-01

    The self-similar spherically symmetric solutions of the Einstein field equation for the case of dust are identified. These form a subclass of the Tolman models. These self-similar models contain the solution recently presented by Chi [J. Math. Phys. 28, 1539 (1987)], thereby refuting the claim of having found a new solution to the Einstein field equations

  5. Mining Diagnostic Assessment Data for Concept Similarity

    Science.gov (United States)

    Madhyastha, Tara; Hunt, Earl

    2009-01-01

    This paper introduces a method for mining multiple-choice assessment data for similarity of the concepts represented by the multiple choice responses. The resulting similarity matrix can be used to visualize the distance between concepts in a lower-dimensional space. This gives an instructor a visualization of the relative difficulty of concepts…

  6. Similarity indices I: what do they measure

    International Nuclear Information System (INIS)

    Johnston, J.W.

    1976-11-01

    A method for estimating the effects of environmental effusions on ecosystems is described. The characteristics of 25 similarity indices used in studies of ecological communities were investigated. The type of data structure, to which these indices are frequently applied, was described as consisting of vectors of measurements on attributes (species) observed in a set of samples. A general similarity index was characterized as the result of a two-step process defined on a pair of vectors. In the first step an attribute similarity score is obtained for each attribute by comparing the attribute values observed in the pair of vectors. The result is a vector of attribute similarity scores. These are combined in the second step to arrive at the similarity index. The operation in the first step was characterized as a function, g, defined on pairs of attribute values. The second operation was characterized as a function, F, defined on the vector of attribute similarity scores from the first step. Usually, F was a simple sum or weighted sum of the attribute similarity scores. It is concluded that similarity indices should not be used as the test statistic to discriminate between two ecological communities

  7. Measuring transferring similarity via local information

    Science.gov (United States)

    Yin, Likang; Deng, Yong

    2018-05-01

    Recommender systems have developed along with the web science, and how to measure the similarity between users is crucial for processing collaborative filtering recommendation. Many efficient models have been proposed (i.g., the Pearson coefficient) to measure the direct correlation. However, the direct correlation measures are greatly affected by the sparsity of dataset. In other words, the direct correlation measures would present an inauthentic similarity if two users have a very few commonly selected objects. Transferring similarity overcomes this drawback by considering their common neighbors (i.e., the intermediates). Yet, the transferring similarity also has its drawback since it can only provide the interval of similarity. To break the limitations, we propose the Belief Transferring Similarity (BTS) model. The contributions of BTS model are: (1) BTS model addresses the issue of the sparsity of dataset by considering the high-order similarity. (2) BTS model transforms uncertain interval to a certain state based on fuzzy systems theory. (3) BTS model is able to combine the transferring similarity of different intermediates using information fusion method. Finally, we compare BTS models with nine different link prediction methods in nine different networks, and we also illustrate the convergence property and efficiency of the BTS model.

  8. On distributional assumptions and whitened cosine similarities

    DEFF Research Database (Denmark)

    Loog, Marco

    2008-01-01

    Recently, an interpretation of the whitened cosine similarity measure as a Bayes decision rule was proposed (C. Liu, "The Bayes Decision Rule Induced Similarity Measures,'' IEEE Trans. Pattern Analysis and Machine Intelligence, vol. 29, no. 6, pp. 1086-1090, June 2007. This communication makes th...

  9. Self-Similar Traffic In Wireless Networks

    OpenAIRE

    Jerjomins, R.; Petersons, E.

    2005-01-01

    Many studies have shown that traffic in Ethernet and other wired networks is self-similar. This paper reveals that wireless network traffic is also self-similar and long-range dependant by analyzing big amount of data captured from the wireless router.

  10. Similarity Structure of Wave-Collapse

    DEFF Research Database (Denmark)

    Rypdal, Kristoffer; Juul Rasmussen, Jens; Thomsen, Kenneth

    1985-01-01

    Similarity transformations of the cubic Schrödinger equation (CSE) are investigated. The transformations are used to remove the explicit time variation in the CSE and reduce it to differential equations in the spatial variables only. Two different methods for similarity reduction are employed and...

  11. Similarity indices I: what do they measure.

    Energy Technology Data Exchange (ETDEWEB)

    Johnston, J.W.

    1976-11-01

    A method for estimating the effects of environmental effusions on ecosystems is described. The characteristics of 25 similarity indices used in studies of ecological communities were investigated. The type of data structure, to which these indices are frequently applied, was described as consisting of vectors of measurements on attributes (species) observed in a set of samples. A general similarity index was characterized as the result of a two-step process defined on a pair of vectors. In the first step an attribute similarity score is obtained for each attribute by comparing the attribute values observed in the pair of vectors. The result is a vector of attribute similarity scores. These are combined in the second step to arrive at the similarity index. The operation in the first step was characterized as a function, g, defined on pairs of attribute values. The second operation was characterized as a function, F, defined on the vector of attribute similarity scores from the first step. Usually, F was a simple sum or weighted sum of the attribute similarity scores. It is concluded that similarity indices should not be used as the test statistic to discriminate between two ecological communities.

  12. Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans

    Directory of Open Access Journals (Sweden)

    Preisinger Rudolf

    2010-01-01

    Full Text Available Abstract Background Sudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies. Methods Neurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR. These investigations were accomplished by MHC genotyping and a PCR screen for Marek's disease virus (MDV. Results Spontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelin-bound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded. Conclusions The paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift.

  13. Information filtering based on transferring similarity.

    Science.gov (United States)

    Sun, Duo; Zhou, Tao; Liu, Jian-Guo; Liu, Run-Ran; Jia, Chun-Xiao; Wang, Bing-Hong

    2009-07-01

    In this Brief Report, we propose an index of user similarity, namely, the transferring similarity, which involves all high-order similarities between users. Accordingly, we design a modified collaborative filtering algorithm, which provides remarkably higher accurate predictions than the standard collaborative filtering. More interestingly, we find that the algorithmic performance will approach its optimal value when the parameter, contained in the definition of transferring similarity, gets close to its critical value, before which the series expansion of transferring similarity is convergent and after which it is divergent. Our study is complementary to the one reported in [E. A. Leicht, P. Holme, and M. E. J. Newman, Phys. Rev. E 73, 026120 (2006)], and is relevant to the missing link prediction problem.

  14. Self-similar continued root approximants

    International Nuclear Information System (INIS)

    Gluzman, S.; Yukalov, V.I.

    2012-01-01

    A novel method of summing asymptotic series is advanced. Such series repeatedly arise when employing perturbation theory in powers of a small parameter for complicated problems of condensed matter physics, statistical physics, and various applied problems. The method is based on the self-similar approximation theory involving self-similar root approximants. The constructed self-similar continued roots extrapolate asymptotic series to finite values of the expansion parameter. The self-similar continued roots contain, as a particular case, continued fractions and Padé approximants. A theorem on the convergence of the self-similar continued roots is proved. The method is illustrated by several examples from condensed-matter physics.

  15. Scalar Similarity for Relaxed Eddy Accumulation Methods

    Science.gov (United States)

    Ruppert, Johannes; Thomas, Christoph; Foken, Thomas

    2006-07-01

    The relaxed eddy accumulation (REA) method allows the measurement of trace gas fluxes when no fast sensors are available for eddy covariance measurements. The flux parameterisation used in REA is based on the assumption of scalar similarity, i.e., similarity of the turbulent exchange of two scalar quantities. In this study changes in scalar similarity between carbon dioxide, sonic temperature and water vapour were assessed using scalar correlation coefficients and spectral analysis. The influence on REA measurements was assessed by simulation. The evaluation is based on observations over grassland, irrigated cotton plantation and spruce forest. Scalar similarity between carbon dioxide, sonic temperature and water vapour showed a distinct diurnal pattern and change within the day. Poor scalar similarity was found to be linked to dissimilarities in the energy contained in the low frequency part of the turbulent spectra ( definition.

  16. Surf similarity and solitary wave runup

    DEFF Research Database (Denmark)

    Fuhrman, David R.; Madsen, Per A.

    2008-01-01

    The notion of surf similarity in the runup of solitary waves is revisited. We show that the surf similarity parameter for solitary waves may be effectively reduced to the beach slope divided by the offshore wave height to depth ratio. This clarifies its physical interpretation relative to a previ...... functional dependence on their respective surf similarity parameters. Important equivalencies in the runup of sinusoidal and solitary waves are thus revealed.......The notion of surf similarity in the runup of solitary waves is revisited. We show that the surf similarity parameter for solitary waves may be effectively reduced to the beach slope divided by the offshore wave height to depth ratio. This clarifies its physical interpretation relative...... to a previous parameterization, which was not given in an explicit form. Good coherency with experimental (breaking) runup data is preserved with this simpler parameter. A recasting of analytical (nonbreaking) runup expressions for sinusoidal and solitary waves additionally shows that they contain identical...

  17. Similarity in Bilateral Isolated Internal Orbital Fractures.

    Science.gov (United States)

    Chen, Hung-Chang; Cox, Jacob T; Sanyal, Abanti; Mahoney, Nicholas R

    2018-04-13

    In evaluating patients sustaining bilateral isolated internal orbital fractures, the authors have observed both similar fracture locations and also similar expansion of orbital volumes. In this study, we aim to investigate if there is a propensity for the 2 orbits to fracture in symmetrically similar patterns when sustaining similar trauma. A retrospective chart review was performed studying all cases at our institution of bilateral isolated internal orbital fractures involving the medial wall and/or the floor at the time of presentation. The similarity of the bilateral fracture locations was evaluated using the Fisher's exact test. The bilateral expanded orbital volumes were analyzed using the Wilcoxon signed-rank test to assess for orbital volume similarity. Twenty-four patients with bilateral internal orbital fractures were analyzed for fracture location similarity. Seventeen patients (70.8%) had 100% concordance in the orbital subregion fractured, and the association between the right and the left orbital fracture subregion locations was statistically significant (P < 0.0001). Fifteen patients were analyzed for orbital volume similarity. The average orbital cavity volume was 31.2 ± 3.8 cm on the right and 32.0 ± 3.7 cm on the left. There was a statistically significant difference between right and left orbital cavity volumes (P = 0.0026). The data from this study suggest that an individual who suffers isolated bilateral internal orbital fractures has a statistically significant similarity in the location of their orbital fractures. However, there does not appear to be statistically significant similarity in the expansion of the orbital volumes in these patients.

  18. Changes in estrogen receptor-alpha and -beta in the infundibular nucleus of the human hypothalamus are related to the occurrence of Alzheimer's disease neuropathology

    NARCIS (Netherlands)

    Hestiantoro, Andon; Swaab, Dick F.

    2004-01-01

    The expression of estrogen receptor (ER)alpha and -beta in the infundibular nucleus of the hypothalamus was studied immunocytochemically in 28 control subjects and 14 patients with Alzheimer's disease (AD). A shift was found from more nuclear staining of ERalpha in young female controls to more

  19. Solution structure of the human signaling protein RACK1

    Directory of Open Access Journals (Sweden)

    Papa Priscila F

    2010-06-01

    Full Text Available Abstract Background The adaptor protein RACK1 (receptor of activated kinase 1 was originally identified as an anchoring protein for protein kinase C. RACK1 is a 36 kDa protein, and is composed of seven WD repeats which mediate its protein-protein interactions. RACK1 is ubiquitously expressed and has been implicated in diverse cellular processes involving: protein translation regulation, neuropathological processes, cellular stress, and tissue development. Results In this study we performed a biophysical analysis of human RACK1 with the aim of obtaining low resolution structural information. Small angle X-ray scattering (SAXS experiments demonstrated that human RACK1 is globular and monomeric in solution and its low resolution structure is strikingly similar to that of an homology model previously calculated by us and to the crystallographic structure of RACK1 isoform A from Arabidopsis thaliana. Both sedimentation velocity and sedimentation equilibrium analytical ultracentrifugation techniques showed that RACK1 is predominantly a monomer of around 37 kDa in solution, but also presents small amounts of oligomeric species. Moreover, hydrodynamic data suggested that RACK1 has a slightly asymmetric shape. The interaction of RACK1 and Ki-1/57 was tested by sedimentation equilibrium. The results suggested that the association between RACK1 and Ki-1/57(122-413 follows a stoichiometry of 1:1. The binding constant (KB observed for RACK1-Ki-1/57(122-413 interaction was of around (1.5 ± 0.2 × 106 M-1 and resulted in a dissociation constant (KD of (0.7 ± 0.1 × 10-6 M. Moreover, the fluorescence data also suggests that the interaction may occur in a cooperative fashion. Conclusion Our SAXS and analytical ultracentrifugation experiments indicated that RACK1 is predominantly a monomer in solution. RACK1 and Ki-1/57(122-413 interact strongly under the tested conditions.

  20. Measure of Node Similarity in Multilayer Networks.

    Directory of Open Access Journals (Sweden)

    Anders Mollgaard

    Full Text Available The weight of links in a network is often related to the similarity of the nodes. Here, we introduce a simple tunable measure for analysing the similarity of nodes across different link weights. In particular, we use the measure to analyze homophily in a group of 659 freshman students at a large university. Our analysis is based on data obtained using smartphones equipped with custom data collection software, complemented by questionnaire-based data. The network of social contacts is represented as a weighted multilayer network constructed from different channels of telecommunication as well as data on face-to-face contacts. We find that even strongly connected individuals are not more similar with respect to basic personality traits than randomly chosen pairs of individuals. In contrast, several socio-demographics variables have a significant degree of similarity. We further observe that similarity might be present in one layer of the multilayer network and simultaneously be absent in the other layers. For a variable such as gender, our measure reveals a transition from similarity between nodes connected with links of relatively low weight to dis-similarity for the nodes connected by the strongest links. We finally analyze the overlap between layers in the network for different levels of acquaintanceships.

  1. Notions of similarity for computational biology models

    KAUST Repository

    Waltemath, Dagmar

    2016-03-21

    Computational models used in biology are rapidly increasing in complexity, size, and numbers. To build such large models, researchers need to rely on software tools for model retrieval, model combination, and version control. These tools need to be able to quantify the differences and similarities between computational models. However, depending on the specific application, the notion of similarity may greatly vary. A general notion of model similarity, applicable to various types of models, is still missing. Here, we introduce a general notion of quantitative model similarities, survey the use of existing model comparison methods in model building and management, and discuss potential applications of model comparison. To frame model comparison as a general problem, we describe a theoretical approach to defining and computing similarities based on different model aspects. Potentially relevant aspects of a model comprise its references to biological entities, network structure, mathematical equations and parameters, and dynamic behaviour. Future similarity measures could combine these model aspects in flexible, problem-specific ways in order to mimic users\\' intuition about model similarity, and to support complex model searches in databases.

  2. Trajectory similarity join in spatial networks

    KAUST Repository

    Shang, Shuo

    2017-09-07

    The matching of similar pairs of objects, called similarity join, is fundamental functionality in data management. We consider the case of trajectory similarity join (TS-Join), where the objects are trajectories of vehicles moving in road networks. Thus, given two sets of trajectories and a threshold θ, the TS-Join returns all pairs of trajectories from the two sets with similarity above θ. This join targets applications such as trajectory near-duplicate detection, data cleaning, ridesharing recommendation, and traffic congestion prediction. With these applications in mind, we provide a purposeful definition of similarity. To enable efficient TS-Join processing on large sets of trajectories, we develop search space pruning techniques and take into account the parallel processing capabilities of modern processors. Specifically, we present a two-phase divide-and-conquer algorithm. For each trajectory, the algorithm first finds similar trajectories. Then it merges the results to achieve a final result. The algorithm exploits an upper bound on the spatiotemporal similarity and a heuristic scheduling strategy for search space pruning. The algorithm\\'s per-trajectory searches are independent of each other and can be performed in parallel, and the merging has constant cost. An empirical study with real data offers insight in the performance of the algorithm and demonstrates that is capable of outperforming a well-designed baseline algorithm by an order of magnitude.

  3. The baryonic self similarity of dark matter

    International Nuclear Information System (INIS)

    Alard, C.

    2014-01-01

    The cosmological simulations indicates that dark matter halos have specific self-similar properties. However, the halo similarity is affected by the baryonic feedback. By using momentum-driven winds as a model to represent the baryon feedback, an equilibrium condition is derived which directly implies the emergence of a new type of similarity. The new self-similar solution has constant acceleration at a reference radius for both dark matter and baryons. This model receives strong support from the observations of galaxies. The new self-similar properties imply that the total acceleration at larger distances is scale-free, the transition between the dark matter and baryons dominated regime occurs at a constant acceleration, and the maximum amplitude of the velocity curve at larger distances is proportional to M 1/4 . These results demonstrate that this self-similar model is consistent with the basics of modified Newtonian dynamics (MOND) phenomenology. In agreement with the observations, the coincidence between the self-similar model and MOND breaks at the scale of clusters of galaxies. Some numerical experiments show that the behavior of the density near the origin is closely approximated by a Einasto profile.

  4. Notions of similarity for computational biology models

    KAUST Repository

    Waltemath, Dagmar; Henkel, Ron; Hoehndorf, Robert; Kacprowski, Tim; Knuepfer, Christian; Liebermeister, Wolfram

    2016-01-01

    Computational models used in biology are rapidly increasing in complexity, size, and numbers. To build such large models, researchers need to rely on software tools for model retrieval, model combination, and version control. These tools need to be able to quantify the differences and similarities between computational models. However, depending on the specific application, the notion of similarity may greatly vary. A general notion of model similarity, applicable to various types of models, is still missing. Here, we introduce a general notion of quantitative model similarities, survey the use of existing model comparison methods in model building and management, and discuss potential applications of model comparison. To frame model comparison as a general problem, we describe a theoretical approach to defining and computing similarities based on different model aspects. Potentially relevant aspects of a model comprise its references to biological entities, network structure, mathematical equations and parameters, and dynamic behaviour. Future similarity measures could combine these model aspects in flexible, problem-specific ways in order to mimic users' intuition about model similarity, and to support complex model searches in databases.

  5. A Similarity Search Using Molecular Topological Graphs

    Directory of Open Access Journals (Sweden)

    Yoshifumi Fukunishi

    2009-01-01

    Full Text Available A molecular similarity measure has been developed using molecular topological graphs and atomic partial charges. Two kinds of topological graphs were used. One is the ordinary adjacency matrix and the other is a matrix which represents the minimum path length between two atoms of the molecule. The ordinary adjacency matrix is suitable to compare the local structures of molecules such as functional groups, and the other matrix is suitable to compare the global structures of molecules. The combination of these two matrices gave a similarity measure. This method was applied to in silico drug screening, and the results showed that it was effective as a similarity measure.

  6. Similarity-based pattern analysis and recognition

    CERN Document Server

    Pelillo, Marcello

    2013-01-01

    This accessible text/reference presents a coherent overview of the emerging field of non-Euclidean similarity learning. The book presents a broad range of perspectives on similarity-based pattern analysis and recognition methods, from purely theoretical challenges to practical, real-world applications. The coverage includes both supervised and unsupervised learning paradigms, as well as generative and discriminative models. Topics and features: explores the origination and causes of non-Euclidean (dis)similarity measures, and how they influence the performance of traditional classification alg

  7. Models of human adamantinomatous craniopharyngioma tissue: Steps toward an effective adjuvant treatment.

    Science.gov (United States)

    Hölsken, Annett; Buslei, Rolf

    2017-05-01

    Even though ACP is a benign tumor, treatment is challenging because of the tumor's eloquent location. Today, with the exception of surgical intervention and irradiation, further treatment options are limited. However, ongoing molecular research in this field provides insights into the pathways involved in ACP pathogenesis and reveal a plethora of druggable targets. In the next step, appropriate models are essential to identify the most suitable and effective substances for clinical practice. Primary cell cultures in low passages provide a proper and rapid tool for initial drug potency testing. The patient-derived xenograft (PDX) model accommodates ACP complexity in that it shows respect to the preserved architecture and similar histological appearance to human tumors and therefore provides the most appropriate means for analyzing pharmacological efficacy. Nevertheless, further research is needed to understand in more detail the biological background of ACP pathogenesis, which provides the identification of the best targets in the hierarchy of signaling cascades. ACP models are also important for the continuous testing of new targeting drugs, to establish precision medicine. © 2017 International Society of Neuropathology.

  8. Heme Oxygenase-1 Activity as a Correlate to Exercise-Mediated Amelioration of Cognitive Decline and Neuropathological Alterations in an Aging Rat Model of Dementia

    Directory of Open Access Journals (Sweden)

    Andrea Kurucz

    2018-01-01

    Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder with cognitive impairment. Physical exercise has long been proven to be beneficial in the disorder. The present study was designed to examine the effect of voluntary exercise on spatial memory, imaging, and pathological abnormalities. Particular focus has been given to the role of heme oxygenase-1 (HO-1—an important cellular cytoprotectant in preserving mental acuity—using an aging rat model of dementia. Male and female Wistar rats were segregated into six groups—namely, (i aged sedentary (control females (ASF, n=8; (ii aged sedentary (control males (ASM, n=8; (iii aged running females (ARF, n=8; (iv aged running males (ARM, n=8; (v young control females (YCF, n=8; and (vi young control males (YCM, n=8. Rats in the ARF and ARM groups had free access to a standardized inbuilt running wheel during the 3-month evaluation period. Spatial memory was investigated using the Morris Water Test, imaging and pathological alterations were assessed using positron emission tomography (PET imaging and histopathological examinations (H&E, Congo red staining, respectively, and HO-1 enzyme activity assays were also conducted. The outcomes suggest that voluntary physical exercise mitigates impaired spatial memory and neuropathological changes exhibited by the aging sedentary group, via elevated HO-1 activity, contributing to the antioxidant capacity in the aging brain.

  9. HYPOTHESIS TESTING WITH THE SIMILARITY INDEX

    Science.gov (United States)

    Mulltilocus DNA fingerprinting methods have been used extensively to address genetic issues in wildlife populations. Hypotheses concerning population subdivision and differing levels of diversity can be addressed through the use of the similarity index (S), a band-sharing coeffic...

  10. On self-similarity of crack layer

    Science.gov (United States)

    Botsis, J.; Kunin, B.

    1987-01-01

    The crack layer (CL) theory of Chudnovsky (1986), based on principles of thermodynamics of irreversible processes, employs a crucial hypothesis of self-similarity. The self-similarity hypothesis states that the value of the damage density at a point x of the active zone at a time t coincides with that at the corresponding point in the initial (t = 0) configuration of the active zone, the correspondence being given by a time-dependent affine transformation of the space variables. In this paper, the implications of the self-similarity hypothesis for qusi-static CL propagation is investigated using polystyrene as a model material and examining the evolution of damage distribution along the trailing edge which is approximated by a straight segment perpendicular to the crack path. The results support the self-similarity hypothesis adopted by the CL theory.

  11. Bilateral Trade Flows and Income Distribution Similarity

    Science.gov (United States)

    2016-01-01

    Current models of bilateral trade neglect the effects of income distribution. This paper addresses the issue by accounting for non-homothetic consumer preferences and hence investigating the role of income distribution in the context of the gravity model of trade. A theoretically justified gravity model is estimated for disaggregated trade data (Dollar volume is used as dependent variable) using a sample of 104 exporters and 108 importers for 1980–2003 to achieve two main goals. We define and calculate new measures of income distribution similarity and empirically confirm that greater similarity of income distribution between countries implies more trade. Using distribution-based measures as a proxy for demand similarities in gravity models, we find consistent and robust support for the hypothesis that countries with more similar income-distributions trade more with each other. The hypothesis is also confirmed at disaggregated level for differentiated product categories. PMID:27137462

  12. Discovering Music Structure via Similarity Fusion

    DEFF Research Database (Denmark)

    for representing music structure is studied in a simplified scenario consisting of 4412 songs and two similarity measures among them. The results suggest that the PLSA model is a useful framework to combine different sources of information, and provides a reasonable space for song representation.......Automatic methods for music navigation and music recommendation exploit the structure in the music to carry out a meaningful exploration of the “song space”. To get a satisfactory performance from such systems, one should incorporate as much information about songs similarity as possible; however...... semantics”, in such a way that all observed similarities can be satisfactorily explained using the latent semantics. Therefore, one can think of these semantics as the real structure in music, in the sense that they can explain the observed similarities among songs. The suitability of the PLSA model...

  13. Abundance estimation of spectrally similar minerals

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2009-07-01

    Full Text Available This paper evaluates a spectral unmixing method for estimating the partial abundance of spectrally similar minerals in complex mixtures. The method requires formulation of a linear function of individual spectra of individual minerals. The first...

  14. Lagrangian-similarity diffusion-deposition model

    International Nuclear Information System (INIS)

    Horst, T.W.

    1979-01-01

    A Lagrangian-similarity diffusion model has been incorporated into the surface-depletion deposition model. This model predicts vertical concentration profiles far downwind of the source that agree with those of a one-dimensional gradient-transfer model

  15. Discovering Music Structure via Similarity Fusion

    DEFF Research Database (Denmark)

    Arenas-García, Jerónimo; Parrado-Hernandez, Emilio; Meng, Anders

    Automatic methods for music navigation and music recommendation exploit the structure in the music to carry out a meaningful exploration of the “song space”. To get a satisfactory performance from such systems, one should incorporate as much information about songs similarity as possible; however...... semantics”, in such a way that all observed similarities can be satisfactorily explained using the latent semantics. Therefore, one can think of these semantics as the real structure in music, in the sense that they can explain the observed similarities among songs. The suitability of the PLSA model...... for representing music structure is studied in a simplified scenario consisting of 4412 songs and two similarity measures among them. The results suggest that the PLSA model is a useful framework to combine different sources of information, and provides a reasonable space for song representation....

  16. Outsourced similarity search on metric data assets

    KAUST Repository

    Yiu, Man Lung

    2012-02-01

    This paper considers a cloud computing setting in which similarity querying of metric data is outsourced to a service provider. The data is to be revealed only to trusted users, not to the service provider or anyone else. Users query the server for the most similar data objects to a query example. Outsourcing offers the data owner scalability and a low-initial investment. The need for privacy may be due to the data being sensitive (e.g., in medicine), valuable (e.g., in astronomy), or otherwise confidential. Given this setting, the paper presents techniques that transform the data prior to supplying it to the service provider for similarity queries on the transformed data. Our techniques provide interesting trade-offs between query cost and accuracy. They are then further extended to offer an intuitive privacy guarantee. Empirical studies with real data demonstrate that the techniques are capable of offering privacy while enabling efficient and accurate processing of similarity queries.

  17. Protein structural similarity search by Ramachandran codes

    Directory of Open Access Journals (Sweden)

    Chang Chih-Hung

    2007-08-01

    Full Text Available Abstract Background Protein structural data has increased exponentially, such that fast and accurate tools are necessary to access structure similarity search. To improve the search speed, several methods have been designed to reduce three-dimensional protein structures to one-dimensional text strings that are then analyzed by traditional sequence alignment methods; however, the accuracy is usually sacrificed and the speed is still unable to match sequence similarity search tools. Here, we aimed to improve the linear encoding methodology and develop efficient search tools that can rapidly retrieve structural homologs from large protein databases. Results We propose a new linear encoding method, SARST (Structural similarity search Aided by Ramachandran Sequential Transformation. SARST transforms protein structures into text strings through a Ramachandran map organized by nearest-neighbor clustering and uses a regenerative approach to produce substitution matrices. Then, classical sequence similarity search methods can be applied to the structural similarity search. Its accuracy is similar to Combinatorial Extension (CE and works over 243,000 times faster, searching 34,000 proteins in 0.34 sec with a 3.2-GHz CPU. SARST provides statistically meaningful expectation values to assess the retrieved information. It has been implemented into a web service and a stand-alone Java program that is able to run on many different platforms. Conclusion As a database search method, SARST can rapidly distinguish high from low similarities and efficiently retrieve homologous structures. It demonstrates that the easily accessible linear encoding methodology has the potential to serve as a foundation for efficient protein structural similarity search tools. These search tools are supposed applicable to automated and high-throughput functional annotations or predictions for the ever increasing number of published protein structures in this post-genomic era.

  18. Similarity search processing. Paralelization and indexing technologies.

    Directory of Open Access Journals (Sweden)

    Eder Dos Santos

    2015-08-01

    The next Scientific-Technical Report addresses the similarity search and the implementation of metric structures on parallel environments. It also presents the state of the art related to similarity search on metric structures and parallelism technologies. Comparative analysis are also proposed, seeking to identify the behavior of a set of metric spaces and metric structures over processing platforms multicore-based and GPU-based.

  19. Parallel trajectory similarity joins in spatial networks

    KAUST Repository

    Shang, Shuo

    2018-04-04

    The matching of similar pairs of objects, called similarity join, is fundamental functionality in data management. We consider two cases of trajectory similarity joins (TS-Joins), including a threshold-based join (Tb-TS-Join) and a top-k TS-Join (k-TS-Join), where the objects are trajectories of vehicles moving in road networks. Given two sets of trajectories and a threshold θ, the Tb-TS-Join returns all pairs of trajectories from the two sets with similarity above θ. In contrast, the k-TS-Join does not take a threshold as a parameter, and it returns the top-k most similar trajectory pairs from the two sets. The TS-Joins target diverse applications such as trajectory near-duplicate detection, data cleaning, ridesharing recommendation, and traffic congestion prediction. With these applications in mind, we provide purposeful definitions of similarity. To enable efficient processing of the TS-Joins on large sets of trajectories, we develop search space pruning techniques and enable use of the parallel processing capabilities of modern processors. Specifically, we present a two-phase divide-and-conquer search framework that lays the foundation for the algorithms for the Tb-TS-Join and the k-TS-Join that rely on different pruning techniques to achieve efficiency. For each trajectory, the algorithms first find similar trajectories. Then they merge the results to obtain the final result. The algorithms for the two joins exploit different upper and lower bounds on the spatiotemporal trajectory similarity and different heuristic scheduling strategies for search space pruning. Their per-trajectory searches are independent of each other and can be performed in parallel, and the mergings have constant cost. An empirical study with real data offers insight in the performance of the algorithms and demonstrates that they are capable of outperforming well-designed baseline algorithms by an order of magnitude.

  20. Parallel trajectory similarity joins in spatial networks

    KAUST Repository

    Shang, Shuo; Chen, Lisi; Wei, Zhewei; Jensen, Christian S.; Zheng, Kai; Kalnis, Panos

    2018-01-01

    The matching of similar pairs of objects, called similarity join, is fundamental functionality in data management. We consider two cases of trajectory similarity joins (TS-Joins), including a threshold-based join (Tb-TS-Join) and a top-k TS-Join (k-TS-Join), where the objects are trajectories of vehicles moving in road networks. Given two sets of trajectories and a threshold θ, the Tb-TS-Join returns all pairs of trajectories from the two sets with similarity above θ. In contrast, the k-TS-Join does not take a threshold as a parameter, and it returns the top-k most similar trajectory pairs from the two sets. The TS-Joins target diverse applications such as trajectory near-duplicate detection, data cleaning, ridesharing recommendation, and traffic congestion prediction. With these applications in mind, we provide purposeful definitions of similarity. To enable efficient processing of the TS-Joins on large sets of trajectories, we develop search space pruning techniques and enable use of the parallel processing capabilities of modern processors. Specifically, we present a two-phase divide-and-conquer search framework that lays the foundation for the algorithms for the Tb-TS-Join and the k-TS-Join that rely on different pruning techniques to achieve efficiency. For each trajectory, the algorithms first find similar trajectories. Then they merge the results to obtain the final result. The algorithms for the two joins exploit different upper and lower bounds on the spatiotemporal trajectory similarity and different heuristic scheduling strategies for search space pruning. Their per-trajectory searches are independent of each other and can be performed in parallel, and the mergings have constant cost. An empirical study with real data offers insight in the performance of the algorithms and demonstrates that they are capable of outperforming well-designed baseline algorithms by an order of magnitude.

  1. Are calanco landforms similar to river basins?

    Science.gov (United States)

    Caraballo-Arias, N A; Ferro, V

    2017-12-15

    In the past badlands have been often considered as ideal field laboratories for studying landscape evolution because of their geometrical similarity to larger fluvial systems. For a given hydrological process, no scientific proof exists that badlands can be considered a model of river basin prototypes. In this paper the measurements carried out on 45 Sicilian calanchi, a type of badlands that appears as a small-scale hydrographic unit, are used to establish their morphological similarity with river systems whose data are available in the literature. At first the geomorphological similarity is studied by identifying the dimensionless groups, which can assume the same value or a scaled one in a fixed ratio, representing drainage basin shape, stream network and relief properties. Then, for each property, the dimensionless groups are calculated for the investigated calanchi and the river basins and their corresponding scale ratio is evaluated. The applicability of Hack's, Horton's and Melton's laws for establishing similarity criteria is also tested. The developed analysis allows to conclude that a quantitative morphological similarity between calanco landforms and river basins can be established using commonly applied dimensionless groups. In particular, the analysis showed that i) calanchi and river basins have a geometrically similar shape respect to the parameters Rf and Re with a scale factor close to 1, ii) calanchi and river basins are similar respect to the bifurcation and length ratios (λ=1), iii) for the investigated calanchi the Melton number assumes values less than that (0.694) corresponding to the river case and a scale ratio ranging from 0.52 and 0.78 can be used, iv) calanchi and river basins have similar mean relief ratio values (λ=1.13) and v) calanchi present active geomorphic processes and therefore fall in a more juvenile stage with respect to river basins. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Structural similarity image quality reliability: Determining parameters and window size

    OpenAIRE

    Silvestre-Blanes, Javier

    2011-01-01

    The need to obtain objective values of the quality of distorted images with respect to the original is fundamental in multimedia and image processing applications. It is generally required that this value correlates well with the human vision system (HVS). In spite of the properties and the general use of the mean square error (MSE) measurement, this has a poor correlation with HSV, which has led to the development of methods such as structural similarity (SSIM). This metric improves the corr...

  3. Distributional Similarity for Chinese: Exploiting Characters and Radicals

    Directory of Open Access Journals (Sweden)

    Peng Jin

    2012-01-01

    Full Text Available Distributional Similarity has attracted considerable attention in the field of natural language processing as an automatic means of countering the ubiquitous problem of sparse data. As a logographic language, Chinese words consist of characters and each of them is composed of one or more radicals. The meanings of characters are usually highly related to the words which contain them. Likewise, radicals often make a predictable contribution to the meaning of a character: characters that have the same components tend to have similar or related meanings. In this paper, we utilize these properties of the Chinese language to improve Chinese word similarity computation. Given a content word, we first extract similar words based on a large corpus and a similarity score for ranking. This rank is then adjusted according to the characters and components shared between the similar word and the target word. Experiments on two gold standard datasets show that the adjusted rank is superior and closer to human judgments than the original rank. In addition to quantitative evaluation, we examine the reasons behind errors drawing on linguistic phenomena for our explanations.

  4. Dissecting the role of non-coding RNAs in the accumulation of amyloid and tau neuropathologies in Alzheimer's disease.

    Science.gov (United States)

    Patrick, Ellis; Rajagopal, Sathyapriya; Wong, Hon-Kit Andus; McCabe, Cristin; Xu, Jishu; Tang, Anna; Imboywa, Selina H; Schneider, Julie A; Pochet, Nathalie; Krichevsky, Anna M; Chibnik, Lori B; Bennett, David A; De Jager, Philip L

    2017-07-01

    Given multiple studies of brain microRNA (miRNA) in relation to Alzheimer's disease (AD) with few consistent results and the heterogeneity of this disease, the objective of this study was to explore their mechanism by evaluating their relation to different elements of Alzheimer's disease pathology, confounding factors and mRNA expression data from the same subjects in the same brain region. We report analyses of expression profiling of miRNA (n = 700 subjects) and lincRNA (n = 540 subjects) from the dorsolateral prefrontal cortex of individuals participating in two longitudinal cohort studies of aging. We confirm the association of two well-established miRNA (miR-132, miR-129) with pathologic AD in our dataset and then further characterize this association in terms of its component neuritic β-amyloid plaques and neurofibrillary tangle pathologies. Additionally, we identify one new miRNA (miR-99) and four lincRNA that are associated with these traits. Many other previously reported associations of microRNA with AD are associated with the confounders quantified in our longitudinal cohort. Finally, by performing analyses integrating both miRNA and RNA sequence data from the same individuals (525 samples), we characterize the impact of AD associated miRNA on human brain expression: we show that the effects of miR-132 and miR-129-5b converge on certain genes such as EP300 and find a role for miR200 and its target genes in AD using an integrated miRNA/mRNA analysis. Overall, miRNAs play a modest role in human AD, but we observe robust evidence that a small number of miRNAs are responsible for specific alterations in the cortical transcriptome that are associated with AD.

  5. Identifying mechanistic similarities in drug responses

    KAUST Repository

    Zhao, C.

    2012-05-15

    Motivation: In early drug development, it would be beneficial to be able to identify those dynamic patterns of gene response that indicate that drugs targeting a particular gene will be likely or not to elicit the desired response. One approach would be to quantitate the degree of similarity between the responses that cells show when exposed to drugs, so that consistencies in the regulation of cellular response processes that produce success or failure can be more readily identified.Results: We track drug response using fluorescent proteins as transcription activity reporters. Our basic assumption is that drugs inducing very similar alteration in transcriptional regulation will produce similar temporal trajectories on many of the reporter proteins and hence be identified as having similarities in their mechanisms of action (MOA). The main body of this work is devoted to characterizing similarity in temporal trajectories/signals. To do so, we must first identify the key points that determine mechanistic similarity between two drug responses. Directly comparing points on the two signals is unrealistic, as it cannot handle delays and speed variations on the time axis. Hence, to capture the similarities between reporter responses, we develop an alignment algorithm that is robust to noise, time delays and is able to find all the contiguous parts of signals centered about a core alignment (reflecting a core mechanism in drug response). Applying the proposed algorithm to a range of real drug experiments shows that the result agrees well with the prior drug MOA knowledge. © The Author 2012. Published by Oxford University Press. All rights reserved.

  6. Semantic similarity between ontologies at different scales

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qingpeng; Haglin, David J.

    2016-04-01

    In the past decade, existing and new knowledge and datasets has been encoded in different ontologies for semantic web and biomedical research. The size of ontologies is often very large in terms of number of concepts and relationships, which makes the analysis of ontologies and the represented knowledge graph computational and time consuming. As the ontologies of various semantic web and biomedical applications usually show explicit hierarchical structures, it is interesting to explore the trade-offs between ontological scales and preservation/precision of results when we analyze ontologies. This paper presents the first effort of examining the capability of this idea via studying the relationship between scaling biomedical ontologies at different levels and the semantic similarity values. We evaluate the semantic similarity between three Gene Ontology slims (Plant, Yeast, and Candida, among which the latter two belong to the same kingdom—Fungi) using four popular measures commonly applied to biomedical ontologies (Resnik, Lin, Jiang-Conrath, and SimRel). The results of this study demonstrate that with proper selection of scaling levels and similarity measures, we can significantly reduce the size of ontologies without losing substantial detail. In particular, the performance of Jiang-Conrath and Lin are more reliable and stable than that of the other two in this experiment, as proven by (a) consistently showing that Yeast and Candida are more similar (as compared to Plant) at different scales, and (b) small deviations of the similarity values after excluding a majority of nodes from several lower scales. This study provides a deeper understanding of the application of semantic similarity to biomedical ontologies, and shed light on how to choose appropriate semantic similarity measures for biomedical engineering.

  7. Clinical features, neurogenetics and neuropathology of the polyglutamine spinocerebellar ataxias type 1, 2, 3, 6 and 7.

    Science.gov (United States)

    Rüb, Udo; Schöls, Ludger; Paulson, Henry; Auburger, Georg; Kermer, Pawel; Jen, Joanna C; Seidel, Kay; Korf, Horst-Werner; Deller, Thomas

    2013-05-01

    The spinocerebellar ataxias type 1 (SCA1), 2 (SCA2), 3 (SCA3), 6 (SCA6) and 7 (SCA7) are genetically defined autosomal dominantly inherited progressive cerebellar ataxias (ADCAs). They belong to the group of CAG-repeat or polyglutamine diseases and share pathologically expanded and meiotically unstable glutamine-encoding CAG-repeats at distinct gene loci encoding elongated polyglutamine stretches in the disease proteins. In recent years, progress has been made in the understanding of the pathogenesis of these currently incurable diseases: Identification of underlying genetic mechanisms made it possible to classify the different ADCAs and to define their clinical and pathological features. Furthermore, advances in molecular biology yielded new insights into the physiological and pathophysiological role of the gene products of SCA1, SCA2, SCA3, SCA6 and SCA7 (i.e. ataxin-1, ataxin-2, ataxin-3, α-1A subunit of the P/Q type voltage-dependent calcium channel, ataxin-7). In the present review we summarize our current knowledge about the polyglutamine ataxias SCA1, SCA2, SCA3, SCA6 and SCA7 and compare their clinical and electrophysiological features, genetic and molecular biological background, as well as their brain pathologies. Furthermore, we provide an overview of the structure, interactions and functions of the different disease proteins. On the basis of these comprehensive data, similarities, differences and possible disease mechanisms are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Measure of Node Similarity in Multilayer Networks

    DEFF Research Database (Denmark)

    Møllgaard, Anders; Zettler, Ingo; Dammeyer, Jesper

    2016-01-01

    The weight of links in a network is often related to the similarity of thenodes. Here, we introduce a simple tunable measure for analysing the similarityof nodes across different link weights. In particular, we use the measure toanalyze homophily in a group of 659 freshman students at a large...... university.Our analysis is based on data obtained using smartphones equipped with customdata collection software, complemented by questionnaire-based data. The networkof social contacts is represented as a weighted multilayer network constructedfrom different channels of telecommunication as well as data...... might bepresent in one layer of the multilayer network and simultaneously be absent inthe other layers. For a variable such as gender, our measure reveals atransition from similarity between nodes connected with links of relatively lowweight to dis-similarity for the nodes connected by the strongest...

  9. A Novel Hybrid Similarity Calculation Model

    Directory of Open Access Journals (Sweden)

    Xiaoping Fan

    2017-01-01

    Full Text Available This paper addresses the problems of similarity calculation in the traditional recommendation algorithms of nearest neighbor collaborative filtering, especially the failure in describing dynamic user preference. Proceeding from the perspective of solving the problem of user interest drift, a new hybrid similarity calculation model is proposed in this paper. This model consists of two parts, on the one hand the model uses the function fitting to describe users’ rating behaviors and their rating preferences, and on the other hand it employs the Random Forest algorithm to take user attribute features into account. Furthermore, the paper combines the two parts to build a new hybrid similarity calculation model for user recommendation. Experimental results show that, for data sets of different size, the model’s prediction precision is higher than the traditional recommendation algorithms.

  10. Universal self-similarity of propagating populations.

    Science.gov (United States)

    Eliazar, Iddo; Klafter, Joseph

    2010-07-01

    This paper explores the universal self-similarity of propagating populations. The following general propagation model is considered: particles are randomly emitted from the origin of a d-dimensional Euclidean space and propagate randomly and independently of each other in space; all particles share a statistically common--yet arbitrary--motion pattern; each particle has its own random propagation parameters--emission epoch, motion frequency, and motion amplitude. The universally self-similar statistics of the particles' displacements and first passage times (FPTs) are analyzed: statistics which are invariant with respect to the details of the displacement and FPT measurements and with respect to the particles' underlying motion pattern. Analysis concludes that the universally self-similar statistics are governed by Poisson processes with power-law intensities and by the Fréchet and Weibull extreme-value laws.

  11. Universal self-similarity of propagating populations

    Science.gov (United States)

    Eliazar, Iddo; Klafter, Joseph

    2010-07-01

    This paper explores the universal self-similarity of propagating populations. The following general propagation model is considered: particles are randomly emitted from the origin of a d -dimensional Euclidean space and propagate randomly and independently of each other in space; all particles share a statistically common—yet arbitrary—motion pattern; each particle has its own random propagation parameters—emission epoch, motion frequency, and motion amplitude. The universally self-similar statistics of the particles’ displacements and first passage times (FPTs) are analyzed: statistics which are invariant with respect to the details of the displacement and FPT measurements and with respect to the particles’ underlying motion pattern. Analysis concludes that the universally self-similar statistics are governed by Poisson processes with power-law intensities and by the Fréchet and Weibull extreme-value laws.

  12. Trajectory similarity join in spatial networks

    KAUST Repository

    Shang, Shuo; Chen, Lisi; Wei, Zhewei; Jensen, Christian S.; Zheng, Kai; Kalnis, Panos

    2017-01-01

    With these applications in mind, we provide a purposeful definition of similarity. To enable efficient TS-Join processing on large sets of trajectories, we develop search space pruning techniques and take into account the parallel processing capabilities of modern processors. Specifically, we present a two-phase divide-and-conquer algorithm. For each trajectory, the algorithm first finds similar trajectories. Then it merges the results to achieve a final result. The algorithm exploits an upper bound on the spatiotemporal similarity and a heuristic scheduling strategy for search space pruning. The algorithm's per-trajectory searches are independent of each other and can be performed in parallel, and the merging has constant cost. An empirical study with real data offers insight in the performance of the algorithm and demonstrates that is capable of outperforming a well-designed baseline algorithm by an order of magnitude.

  13. Phonological similarity in working memory span tasks.

    Science.gov (United States)

    Chow, Michael; Macnamara, Brooke N; Conway, Andrew R A

    2016-08-01

    In a series of four experiments, we explored what conditions are sufficient to produce a phonological similarity facilitation effect in working memory span tasks. By using the same set of memoranda, but differing the secondary-task requirements across experiments, we showed that a phonological similarity facilitation effect is dependent upon the semantic relationship between the memoranda and the secondary-task stimuli, and is robust to changes in the representation, ordering, and pool size of the secondary-task stimuli. These findings are consistent with interference accounts of memory (Brown, Neath, & Chater, Psychological Review, 114, 539-576, 2007; Oberauer, Lewandowsky, Farrell, Jarrold, & Greaves, Psychonomic Bulletin & Review, 19, 779-819, 2012), whereby rhyming stimuli provide a form of categorical similarity that allows distractors to be excluded from retrieval at recall.

  14. Unveiling Music Structure Via PLSA Similarity Fusion

    DEFF Research Database (Denmark)

    Arenas-García, Jerónimo; Meng, Anders; Petersen, Kaare Brandt

    2007-01-01

    Nowadays there is an increasing interest in developing methods for building music recommendation systems. In order to get a satisfactory performance from such a system, one needs to incorporate as much information about songs similarity as possible; however, how to do so is not obvious. In this p......Nowadays there is an increasing interest in developing methods for building music recommendation systems. In order to get a satisfactory performance from such a system, one needs to incorporate as much information about songs similarity as possible; however, how to do so is not obvious...... observed similarities can be satisfactorily explained using the latent semantics. Additionally, this approach significantly simplifies the song retrieval phase, leading to a more practical system implementation. The suitability of the PLSA model for representing music structure is studied in a simplified...

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

    Science.gov (United States)

    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.

  16. Similarity joins in relational database systems

    CERN Document Server

    Augsten, Nikolaus

    2013-01-01

    State-of-the-art database systems manage and process a variety of complex objects, including strings and trees. For such objects equality comparisons are often not meaningful and must be replaced by similarity comparisons. This book describes the concepts and techniques to incorporate similarity into database systems. We start out by discussing the properties of strings and trees, and identify the edit distance as the de facto standard for comparing complex objects. Since the edit distance is computationally expensive, token-based distances have been introduced to speed up edit distance comput

  17. Outsourced Similarity Search on Metric Data Assets

    DEFF Research Database (Denmark)

    Yiu, Man Lung; Assent, Ira; Jensen, Christian S.

    2012-01-01

    . Outsourcing offers the data owner scalability and a low initial investment. The need for privacy may be due to the data being sensitive (e.g., in medicine), valuable (e.g., in astronomy), or otherwise confidential. Given this setting, the paper presents techniques that transform the data prior to supplying......This paper considers a cloud computing setting in which similarity querying of metric data is outsourced to a service provider. The data is to be revealed only to trusted users, not to the service provider or anyone else. Users query the server for the most similar data objects to a query example...

  18. Measure of Node Similarity in Multilayer Networks

    DEFF Research Database (Denmark)

    Møllgaard, Anders; Zettler, Ingo; Dammeyer, Jesper

    2016-01-01

    university.Our analysis is based on data obtained using smartphones equipped with customdata collection software, complemented by questionnaire-based data. The networkof social contacts is represented as a weighted multilayer network constructedfrom different channels of telecommunication as well as data...... might bepresent in one layer of the multilayer network and simultaneously be absent inthe other layers. For a variable such as gender, our measure reveals atransition from similarity between nodes connected with links of relatively lowweight to dis-similarity for the nodes connected by the strongest...

  19. Cultural similarity and adjustment of expatriate academics

    DEFF Research Database (Denmark)

    Selmer, Jan; Lauring, Jakob

    2009-01-01

    The findings of a number of recent empirical studies of business expatriates, using different samples and methodologies, seem to support the counter-intuitive proposition that cultural similarity may be as difficult to adjust to as cultural dissimilarity. However, it is not obvious...... and non-EU countries. Results showed that although the perceived cultural similarity between host and home country for the two groups of investigated respondents was different, there was neither any difference in their adjustment nor in the time it took for them to become proficient. Implications...

  20. Sporadic Creutzfeldt-Jakob disease: a clinico-neuropathological analysis of nine definite cases Doença de Creutzfeldt-Jakob do tipo esporádico: análise clínico-neuropatológica de nove casos da forma definida

    Directory of Open Access Journals (Sweden)

    CARLOS M. DE CASTRO COSTA

    1998-09-01

    Full Text Available The authors have analyzed clinico-neuropathologically nine cases of the definite sporadic form of Creutzfeldt-Jakob disease (CJD. All cases were female, with mean age of 62.7 years. Eighty-nine percent of the patients exhibited prodromal and initial psychiatric symptoms; definite signs of dementia, and myoclonus were present in 100% of cases. The EEG was abnormal in all cases and pseudoperiodic paroxysms were present in 56% of the patients. Their evolution time ranged from 3 to 19 months. Neuropathologically, brain and cerebellar atrophy, spongiosis, astrocytosis and neuronal loss were present in 100% of the patients. In 5 (56% of these 9 cases, prion protein (PrP amyloid plaques were detected in the cerebellum, by optical- and electronmicroscopy. There was a positive correlation between the number of plaques and the evolution time. The authors outline the similarities of their cases in the elderly with the new variant of CJD described in young people.Os autores analisaram, do ponto de vista clínico e neuropatológico, nove casos da forma esporádica definida da doença de Creutzfeldt-Jakob (DCJ. Todos eles eram mulheres, com idade média de 62,7 anos. Oitenta e nove por cento dos pacientes exibiram sintomas psiquiátricos prodrômicos e iniciais; sinais típicos de demência e mioclonias estavam presentes em 100% deles. O EEG foi anormal em todos os casos e apresentou paroxismos pseudoperiódicos em 56% dos pacientes. O tempo de evolução da doença variou de 3 a 19 meses. Do ponto de vista neuropatológico, atrofia cerebral e cerebelar, espongiose, astrocitose e perda neuronal estavam presentes em 100% dos pacientes. Em 5 (56% dos 9 casos, foi evidenciada, por microscopia óptica e eletrônica, a presença de placas amilóides de proteína prion (PrP no cerebelo. Havia correlação positiva entre o número de placas e o tempo de evolução da doença. Os autores salientam as semelhanças desses seus casos de pacientes idosos com a nova

  1. Nuclear markers reveal that inter-lake cichlids' similar morphologies do not reflect similar genealogy.

    Science.gov (United States)

    Kassam, Daud; Seki, Shingo; Horic, Michio; Yamaoka, Kosaku

    2006-08-01

    The apparent inter-lake morphological similarity among East African Great Lakes' cichlid species/genera has left evolutionary biologists asking whether such similarity is due to sharing of common ancestor or mere convergent evolution. In order to answer such question, we first used Geometric Morphometrics, GM, to quantify morphological similarity and then subsequently used Amplified Fragment Length Polymorphism, AFLP, to determine if similar morphologies imply shared ancestry or convergent evolution. GM revealed that not all presumed morphological similar pairs were indeed similar, and the dendrogram generated from AFLP data indicated distinct clusters corresponding to each lake and not inter-lake morphological similar pairs. Such results imply that the morphological similarity is due to convergent evolution and not shared ancestry. The congruency of GM and AFLP generated dendrograms imply that GM is capable of picking up phylogenetic signal, and thus GM can be potential tool in phylogenetic systematics.

  2. Clustering biomolecular complexes by residue contacts similarity

    NARCIS (Netherlands)

    Garcia Lopes Maia Rodrigues, João; Trellet, Mikaël; Schmitz, Christophe; Kastritis, Panagiotis; Karaca, Ezgi; Melquiond, Adrien S J; Bonvin, Alexandre M J J; Garcia Lopes Maia Rodrigues, João

    Inaccuracies in computational molecular modeling methods are often counterweighed by brute-force generation of a plethora of putative solutions. These are then typically sieved via structural clustering based on similarity measures such as the root mean square deviation (RMSD) of atomic positions.

  3. Similarity principles for equipment qualification by experience

    International Nuclear Information System (INIS)

    Kana, D.D.; Pomerening, D.J.

    1988-07-01

    A methodology is developed for seismic qualification of nuclear plant equipment by applying similarity principles to existing experience data. Experience data are available from previous qualifications by analysis or testing, or from actual earthquake events. Similarity principles are defined in terms of excitation, equipment physical characteristics, and equipment response. Physical similarity is further defined in terms of a critical transfer function for response at a location on a primary structure, whose response can be assumed directly related to ultimate fragility of the item under elevated levels of excitation. Procedures are developed for combining experience data into composite specifications for qualification of equipment that can be shown to be physically similar to the reference equipment. Other procedures are developed for extending qualifications beyond the original specifications under certain conditions. Some examples for application of the procedures and verification of them are given for certain cases that can be approximated by a two degree of freedom simple primary/secondary system. Other examples are based on use of actual test data available from previous qualifications. Relationships of the developments with other previously-published methods are discussed. The developments are intended to elaborate on the rather broad revised guidelines developed by the IEEE 344 Standards Committee for equipment qualification in new nuclear plants. However, the results also contribute to filling a gap that exists between the IEEE 344 methodology and that previously developed by the Seismic Qualification Utilities Group. The relationship of the results to safety margin methodology is also discussed. (author)

  4. 7 CFR 51.1997 - Similar type.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Similar type. 51.1997 Section 51.1997 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946...

  5. Efficient Similarity Retrieval in Music Databases

    DEFF Research Database (Denmark)

    Ruxanda, Maria Magdalena; Jensen, Christian Søndergaard

    2006-01-01

    Audio music is increasingly becoming available in digital form, and the digital music collections of individuals continue to grow. Addressing the need for effective means of retrieving music from such collections, this paper proposes new techniques for content-based similarity search. Each music...

  6. Similarity search of business process models

    NARCIS (Netherlands)

    Dumas, M.; García-Bañuelos, L.; Dijkman, R.M.

    2009-01-01

    Similarity search is a general class of problems in which a given object, called a query object, is compared against a collection of objects in order to retrieve those that most closely resemble the query object. This paper reviews recent work on an instance of this class of problems, where the

  7. Evaluating gender similarities and differences using metasynthesis.

    Science.gov (United States)

    Zell, Ethan; Krizan, Zlatan; Teeter, Sabrina R

    2015-01-01

    Despite the common lay assumption that males and females are profoundly different, Hyde (2005) used data from 46 meta-analyses to demonstrate that males and females are highly similar. Nonetheless, the gender similarities hypothesis has remained controversial. Since Hyde's provocative report, there has been an explosion of meta-analytic interest in psychological gender differences. We utilized this enormous collection of 106 meta-analyses and 386 individual meta-analytic effects to reevaluate the gender similarities hypothesis. Furthermore, we employed a novel data-analytic approach called metasynthesis (Zell & Krizan, 2014) to estimate the average difference between males and females and to explore moderators of gender differences. The average, absolute difference between males and females across domains was relatively small (d = 0.21, SD = 0.14), with the majority of effects being either small (46%) or very small (39%). Magnitude of differences fluctuated somewhat as a function of the psychological domain (e.g., cognitive variables, social and personality variables, well-being), but remained largely constant across age, culture, and generations. These findings provide compelling support for the gender similarities hypothesis, but also underscore conditions under which gender differences are most pronounced. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  8. Measuring structural similarity in large online networks.

    Science.gov (United States)

    Shi, Yongren; Macy, Michael

    2016-09-01

    Structural similarity based on bipartite graphs can be used to detect meaningful communities, but the networks have been tiny compared to massive online networks. Scalability is important in applications involving tens of millions of individuals with highly skewed degree distributions. Simulation analysis holding underlying similarity constant shows that two widely used measures - Jaccard index and cosine similarity - are biased by the distribution of out-degree in web-scale networks. However, an alternative measure, the Standardized Co-incident Ratio (SCR), is unbiased. We apply SCR to members of Congress, musical artists, and professional sports teams to show how massive co-following on Twitter can be used to map meaningful affiliations among cultural entities, even in the absence of direct connections to one another. Our results show how structural similarity can be used to map cultural alignments and demonstrate the potential usefulness of social media data in the study of culture, politics, and organizations across the social and behavioral sciences. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Phonological Similarity in American Sign Language.

    Science.gov (United States)

    Hildebrandt, Ursula; Corina, David

    2002-01-01

    Investigates deaf and hearing subjects' ratings of American Sign Language (ASL) signs to assess whether linguistic experience shapes judgments of sign similarity. Findings are consistent with linguistic theories that posit movement and location as core structural elements of syllable structure in ASL. (Author/VWL)

  10. Structural similarity and category-specificity

    DEFF Research Database (Denmark)

    Gerlach, Christian; Law, Ian; Paulson, Olaf B

    2004-01-01

    It has been suggested that category-specific recognition disorders for natural objects may reflect that natural objects are more structurally (visually) similar than artefacts and therefore more difficult to recognize following brain damage. On this account one might expect a positive relationshi...

  11. Music Retrieval based on Melodic Similarity

    NARCIS (Netherlands)

    Typke, R.

    2007-01-01

    This thesis introduces a method for measuring melodic similarity for notated music such as MIDI files. This music search algorithm views music as sets of notes that are represented as weighted points in the two-dimensional space of time and pitch. Two point sets can be compared by calculating how

  12. Measurement of Similarity in Academic Contexts

    Directory of Open Access Journals (Sweden)

    Omid Mahian

    2017-06-01

    Full Text Available We propose some reflections, comments and suggestions about the measurement of similar and matched content in scientific papers and documents, and the need to develop appropriate tools and standards for an ethically fair and equitable treatment of authors.

  13. Appropriate Similarity Measures for Author Cocitation Analysis

    NARCIS (Netherlands)

    N.J.P. van Eck (Nees Jan); L. Waltman (Ludo)

    2007-01-01

    textabstractWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of

  14. Similarity of Experience and Empathy in Preschoolers.

    Science.gov (United States)

    Barnett, Mark A.

    The present study examined the role of similarity of experience in young children's affective reactions to others. Some preschoolers played one of two games (Puzzle Board or Buckets) and were informed that they had either failed or succeeded; others merely observed the games being played and were given no evaluative feedback. Subsequently, each…

  15. Cultural Similarities and Differences on Idiom Translation

    Institute of Scientific and Technical Information of China (English)

    黄频频; 陈于全

    2010-01-01

    Both English and Chinese are abound with idioms. Idioms are an important part of the hnguage and culture of a society. English and Chinese idioms carved with cultural characteristics account for a great part in the tramlation. This paper studies the translation of idioms concerning their cultural similarities, cultural differences and transhtion principles.

  16. Learning by similarity in coordination problems

    Czech Academy of Sciences Publication Activity Database

    Steiner, Jakub; Stewart, C.

    -, č. 324 (2007), s. 1-40 ISSN 1211-3298 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:AV0Z70850503 Keywords : similarity * learning * case-based reasoning Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp324.pdf

  17. Outsourced similarity search on metric data assets

    KAUST Repository

    Yiu, Man Lung; Assent, Ira; Jensen, Christian Sø ndergaard; Kalnis, Panos

    2012-01-01

    for the most similar data objects to a query example. Outsourcing offers the data owner scalability and a low-initial investment. The need for privacy may be due to the data being sensitive (e.g., in medicine), valuable (e.g., in astronomy), or otherwise

  18. Extending the Similarity-Attraction Effect : The effects of When-Similarity in mediated communication

    NARCIS (Netherlands)

    Kaptein, M.C.; Castaneda, D.; Fernandez, N.; Nass, C.

    2014-01-01

    The feeling of connectedness experienced in computer-mediated relationships can be explained by the similarity-attraction effect (SAE). Though SAE is well established in psychology, the effects of some types of similarity have not yet been explored. In 2 studies, we demonstrate similarity-attraction

  19. Investigating Correlation between Protein Sequence Similarity and Semantic Similarity Using Gene Ontology Annotations.

    Science.gov (United States)

    Ikram, Najmul; Qadir, Muhammad Abdul; Afzal, Muhammad Tanvir

    2018-01-01

    Sequence similarity is a commonly used measure to compare proteins. With the increasing use of ontologies, semantic (function) similarity is getting importance. The correlation between these measures has been applied in the evaluation of new semantic similarity methods, and in protein function prediction. In this research, we investigate the relationship between the two similarity methods. The results suggest absence of a strong correlation between sequence and semantic similarities. There is a large number of proteins with low sequence similarity and high semantic similarity. We observe that Pearson's correlation coefficient is not sufficient to explain the nature of this relationship. Interestingly, the term semantic similarity values above 0 and below 1 do not seem to play a role in improving the correlation. That is, the correlation coefficient depends only on the number of common GO terms in proteins under comparison, and the semantic similarity measurement method does not influence it. Semantic similarity and sequence similarity have a distinct behavior. These findings are of significant effect for future works on protein comparison, and will help understand the semantic similarity between proteins in a better way.

  20. BLAST and FASTA similarity searching for multiple sequence alignment.

    Science.gov (United States)

    Pearson, William R

    2014-01-01

    BLAST, FASTA, and other similarity searching programs seek to identify homologous proteins and DNA sequences based on excess sequence similarity. If two sequences share much more similarity than expected by chance, the simplest explanation for the excess similarity is common ancestry-homology. The most effective similarity searches compare protein sequences, rather than DNA sequences, for sequences that encode proteins, and use expectation values, rather than percent identity, to infer homology. The BLAST and FASTA packages of sequence comparison programs provide programs for comparing protein and DNA sequences to protein databases (the most sensitive searches). Protein and translated-DNA comparisons to protein databases routinely allow evolutionary look back times from 1 to 2 billion years; DNA:DNA searches are 5-10-fold less sensitive. BLAST and FASTA can be run on popular web sites, but can also be downloaded and installed on local computers. With local installation, target databases can be customized for the sequence data being characterized. With today's very large protein databases, search sensitivity can also be improved by searching smaller comprehensive databases, for example, a complete protein set from an evolutionarily neighboring model organism. By default, BLAST and FASTA use scoring strategies target for distant evolutionary relationships; for comparisons involving short domains or queries, or searches that seek relatively close homologs (e.g. mouse-human), shallower scoring matrices will be more effective. Both BLAST and FASTA provide very accurate statistical estimates, which can be used to reliably identify protein sequences that diverged more than 2 billion years ago.

  1. Similarity relations in visual search predict rapid visual categorization

    Science.gov (United States)

    Mohan, Krithika; Arun, S. P.

    2012-01-01

    How do we perform rapid visual categorization?It is widely thought that categorization involves evaluating the similarity of an object to other category items, but the underlying features and similarity relations remain unknown. Here, we hypothesized that categorization performance is based on perceived similarity relations between items within and outside the category. To this end, we measured the categorization performance of human subjects on three diverse visual categories (animals, vehicles, and tools) and across three hierarchical levels (superordinate, basic, and subordinate levels among animals). For the same subjects, we measured their perceived pair-wise similarities between objects using a visual search task. Regardless of category and hierarchical level, we found that the time taken to categorize an object could be predicted using its similarity to members within and outside its category. We were able to account for several classic categorization phenomena, such as (a) the longer times required to reject category membership; (b) the longer times to categorize atypical objects; and (c) differences in performance across tasks and across hierarchical levels. These categorization times were also accounted for by a model that extracts coarse structure from an image. The striking agreement observed between categorization and visual search suggests that these two disparate tasks depend on a shared coarse object representation. PMID:23092947

  2. Administration of a selective β2 adrenergic receptor antagonist exacerbates neuropathology and cognitive deficits in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Branca, Caterina; Wisely, Elena V; Hartman, Lauren K; Caccamo, Antonella; Oddo, Salvatore

    2014-12-01

    Currently, there are no available approaches to cure or slow down the progression of Alzheimer's disease (AD), which is characterized by the accumulation of extracellular amyloid-β (Aβ) deposits and intraneuronal tangles that comprised hyperphosphorylated tau. The β2 adrenergic receptors (β2ARs) are expressed throughout the cortex and hippocampus and play a key role in cognitive functions. Alterations in the function of these receptors have been linked to AD; however, these data remain controversial as apparent contradicting reports have been published. Given the current demographics of growing elderly population and the high likelihood of concurrent β-blocker use for other chronic conditions, more studies into the role of this receptor in AD animal models are needed. Here, we show that administration of ICI 118,551 (ICI), a selective β2AR antagonist, exacerbates cognitive deficits in a mouse model of AD, the 3xTg-AD mice. Neuropathologically, ICI increased Aβ levels and Aβ plaque burden. Concomitantly, ICI-treated 3xTg-AD mice showed an increase in tau phosphorylation and accumulation. Mechanistically, these changes were linked to an increase in amyloidogenic amyloid precursor protein processing. These results suggest that under the conditions used here, selective pharmacologic inhibition of β2ARs has detrimental effects on AD-like pathology in mice. Overall, these studies strengthen the notion that the link between β2ARs and AD is likely highly complex and suggest caution in generalizing the beneficial effects of β blockers on AD. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Role of Endoplasmic Reticulum Stress in Learning and Memory Impairment and Alzheimer's Disease-Like Neuropathology in the PS19 and APPSwe Mouse Models of Tauopathy and Amyloidosis.

    Science.gov (United States)

    Briggs, Denise Isabelle; Defensor, Erwin; Memar Ardestani, Pooneh; Yi, Bitna; Halpain, Michelle; Seabrook, Guy; Shamloo, Mehrdad

    2017-01-01

    Emerging evidence suggests that endoplasmic reticulum (ER) stress may be involved in the pathogenesis of Alzheimer's disease (AD). Recently, pharmacological modulation of the eukaryotic translation initiation factor-2 (eIF2α) pathway was achieved using an integrated stress response inhibitor (ISRIB). While members of this signaling cascade have been suggested as potential therapeutic targets for neurodegeneration, the biological significance of this pathway has not been comprehensively assessed in animal models of AD. The present study investigated the ER stress pathway and its long-term modulation utilizing in vitro and in vivo experimental models of tauopathy (MAPT P301S)PS19 and amyloidosis (APP Swe ). We report that thapsigargin induces activating transcription factor-4 (ATF4) in primary cortical neurons (PCNs) derived from rat and APP Swe nontransgenic (nTg) and transgenic (Tg) mice. ISRIB mitigated the induction of ATF4 in PCNs generated from wild-type (WT) but not APP Swe mice despite partially restoring thapsigargin-induced translational repression in nTg PCNs. In vivo , C57BL/6J and PS19 mice received prolonged, once-daily administration of ISRIB. While the compound was well tolerated by PS19 and C57BL/6J mice, APP Swe mice treated per this schedule displayed significant mortality. Thus, the dose was reduced and administered only on behavioral test days. ISRIB did not improve learning and memory function in APP Swe Tg mice. While ISRIB did not reduce tau-related neuropathology in PS19 Tg mice, no evidence of ER stress-related dysfunction was observed in either of these Tg models. Taken together, the significance of ER stress and the relevance of these models to the etiology of AD require further investigation.

  4. Neurobehavioral, neuropathological and biochemical profiles in a novel mouse model of co-morbid post-traumatic stress disorder and mild traumatic brain injury

    Science.gov (United States)

    Ojo, Joseph O.; Greenberg, M. Banks; Leary, Paige; Mouzon, Benoit; Bachmeier, Corbin; Mullan, Michael; Diamond, David M.; Crawford, Fiona

    2014-01-01

    Co-morbid mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) has become the signature disorder for returning combat veterans. The clinical heterogeneity and overlapping symptomatology of mTBI and PTSD underscore the need to develop a preclinical model that will enable the characte