WorldWideScience

Sample records for human molecular neuro

  1. The human resource crisis in neuro-ophthalmology.

    Science.gov (United States)

    Frohman, Larry P

    2008-09-01

    Neuro-ophthalmology is facing a serious human resource issue. Few are entering the subspecialty, which is perceived as being poorly compensated compared with other subspecialties of ophthalmology. The low compensation comes from the fact that 1) non-procedural encounters remain undervalued, 2) efforts that benefit other medical specialists are not counted, and 3) the relatively low expenses of neuro-ophthalmologists are not factored into compensation formulas. Mission-based budgeting, which forces academic departments to be financially accountable without the expectation of fiscal relief from medical schools or practice plans, has exacerbated the compensation issue. Solutions must come from within neuro-ophthalmology, academic departments, medical schools, and medical practice plans. They include 1) providing educational resources so that neuro-ophthalmologists need not spend so much time teaching the basics, 2) factoring into compensation the impact of neuro-ophthalmologists in teaching and on revenue generation by procedure-based specialists, 3) improving the efficiency of neuro-ophthalmologists in their consultative practices by providing ample clerical support and other measures, 4) providing contractual salary compensation by departments such as neurosurgery to recognize the contributions made by neuro-ophthalmologists, and 5) reorganizing the academic clinical effort as multidisciplinary rather than departmental.

  2. Structure of neuro-endocrine and neuro-epithelial interactions in human foetal pancreas.

    Science.gov (United States)

    Krivova, Yuliya; Proshchina, Alexandra; Barabanov, Valeriy; Leonova, Olga; Saveliev, Sergey

    2016-12-01

    In the pancreas of many mammals including humans, endocrine islet cells can be integrated with the nervous system components into neuro-insular complexes. The mechanism of the formation of such complexes is not clearly understood. The present study evaluated the interactions between the nervous system components, epithelial cells and endocrine cells in the human pancreas. Foetal pancreas, gestational age 19-23 weeks (13 cases) and 30-34 weeks (7 cases), were studied using double immunohistochemical labeling with neural markers (S100 protein and beta III tubulin), epithelial marker (cytokeratin 19 (CK19)) and antibodies to insulin and glucagon. We first analyse the structure of neuro-insular complexes using confocal microscopy and provide immunohistochemical evidences of the presence of endocrine cells within the ganglia or inside the nerve bundles. We showed that the nervous system components contact with the epithelial cells located in ducts or in clusters outside the ductal epithelium and form complexes with separate epithelial cells. We observed CK19-positive cells inside the ganglia and nerve bundles which were located separately or were integrated with the islets. Therefore, we conclude that neuro-insular complexes may forms as a result of integration between epithelial cells and nervous system components at the initial stages of islets formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Molecular Pathology of Neuro-AIDS (CNS-HIV

    Directory of Open Access Journals (Sweden)

    Eliezer Masliah

    2009-03-01

    Full Text Available The cognitive deficits in patients with HIV profoundly affect the quality of life of people living with this disease and have often been linked to the neuro-inflammatory condition known as HIV encephalitis (HIVE. With the advent of more effective anti-retroviral therapies, HIVE has shifted from a sub-acute to a chronic condition. The neurodegenerative process in patients with HIVE is characterized by synaptic and dendritic damage to pyramidal neurons, loss of calbindin-immunoreactive interneurons and myelin loss. The mechanisms leading to neurodegeneration in HIVE might involve a variety of pathways, and several lines of investigation have found that interference with signaling factors mediating neuroprotection might play an important role. These signaling pathways include, among others, the GSK3b, CDK5, ERK, Pyk2, p38 and JNK cascades. Of these, GSK3b has been a primary focus of many previous studies showing that in infected patients, HIV proteins and neurotoxins secreted by immune-activated cells in the brain abnormally activate this pathway, which is otherwise regulated by growth factors such as FGF. Interestingly, modulation of the GSK3b signaling pathway by FGF1 or GSK3b inhibitors (lithium, valproic acid is protective against HIV neurotoxicity, and several pilot clinical trials have demonstrated cognitive improvements in HIV patients treated with GSK3b inhibitors. In addition to the GSK3b pathway, the CDK5 pathway has recently been implicated as a mediator of neurotoxicity in HIV, and HIV proteins might activate this pathway and subsequently disrupt the diverse processes that CDK5 regulates, including synapse formation and plasticity and neurogenesis. Taken together, the GSK3b and CDK5 signaling pathways are important regulators of neurotoxicity in HIV, and modulation of these factors might have therapeutic potential in the treatment of patients suffering from HIVE. In this context, the subsequent sections will focus on reviewing the

  4. Three Dimensional Human Neuro-Spheroid Model of Alzheimer's Disease Based on Differentiated Induced Pluripotent Stem Cells.

    Directory of Open Access Journals (Sweden)

    Han-Kyu Lee

    Full Text Available The testing of candidate drugs to slow progression of Alzheimer's disease (AD requires clinical trials that are lengthy and expensive. Efforts to model the biochemical milieu of the AD brain may be greatly facilitated by combining two cutting edge technologies to generate three-dimensional (3D human neuro-spheroid from induced pluripotent stem cells (iPSC derived from AD subjects. We created iPSC from blood cells of five AD patients and differentiated them into 3D human neuronal culture. We characterized neuronal markers of our 3D neurons by immunocytochemical staining to validate the differentiation status. To block the generation of pathologic amyloid β peptides (Aβ, the 3D-differentiated AD neurons were treated with inhibitors targeting β-secretase (BACE1 and γ-secretases. As predicted, both BACE1 and γ-secretase inhibitors dramatically decreased Aβ generation in iPSC-derived neural cells derived from all five AD patients, under standard two-dimensional (2D differentiation conditions. However, BACE1 and γ-secretase inhibitors showed less potency in decreasing Aβ levels in neural cells differentiated under 3D culture conditions. Interestingly, in a single subject AD1, we found that BACE1 inhibitor treatment was not able to significantly reduce Aβ42 levels. To investigate underlying molecular mechanisms, we performed proteomic analysis of 3D AD human neuronal cultures including AD1. Proteomic analysis revealed specific reduction of several proteins that might contribute to a poor inhibition of BACE1 in subject AD1. To our knowledge, this is the first iPSC-differentiated 3D neuro-spheroid model derived from AD patients' blood. Our results demonstrate that our 3D human neuro-spheroid model can be a physiologically relevant and valid model for testing efficacy of AD drug.

  5. Ontogeny of neuro-insular complexes and islets innervation in the human pancreas.

    Directory of Open Access Journals (Sweden)

    Alexandra E. Proshchina

    2014-04-01

    Full Text Available The ontogeny of the neuro-insular complexes (NIC and the islets innervation in human pancreas has not been studied in detail. Our aim was to describe the developmental dynamics and distribution of the nervous system structures in the endocrine part of human pancreas. We used doublestaining with antibodies specific to pan-neural markers (neuron-specific enolase (NSE and S100 protein and to hormones of pancreatic endocrine cells. NSE and S100-positive nerves and ganglia were identified in the human fetal pancreas from gestation week (gw 10 onwards. Later the density of S100 and NSE-positive fibers increased. In adults this network was sparse. The islets innervation started to form from gw 14. NSE-containing endocrine cells were identified from gw 12 onwards. Additionally, S100-positive cells were detected both in the periphery and within some of the islets starting at gw 14. The analysis of islets innervation has shown that the fetal pancreas contained neuro-insular complexes and the number of these complexes was reduced in adults. The highest density of neuro-insular complexes is detected during middle and late fetal periods, when the mosaic islets, typical for adults, form. The close integration between the developing pancreatic islets and the nervous system structures may play an important role not only in the hormone secretion, but also in the islets morphogenesis.

  6. Integrating molecular markers into the World Health Organization classification of CNS tumors: a survey of the neuro-oncology community.

    Science.gov (United States)

    Aldape, Kenneth; Nejad, Romina; Louis, David N; Zadeh, Gelareh

    2017-03-01

    Molecular markers provide important biological and clinical information related to the classification of brain tumors, and the integration of relevant molecular parameters into brain tumor classification systems has been a widely discussed topic in neuro-oncology over the past decade. With recent advances in the development of clinically relevant molecular signatures and the 2016 World Health Organization (WHO) update, the views of the neuro-oncology community on such changes would be informative for implementing this process. A survey with 8 questions regarding molecular markers in tumor classification was sent to an email list of Society for Neuro-Oncology members and attendees of prior meetings (n=5065). There were 403 respondents. Analysis was performed using whole group response, based on self-reported subspecialty. The survey results show overall strong support for incorporating molecular knowledge into the classification and clinical management of brain tumors. Across all 7 subspecialty groups, ≥70% of respondents agreed to this integration. Interestingly, some variability is seen among subspecialties, notably with lowest support from neuropathologists, which may reflect their roles in implementing such diagnostic technologies. Based on a survey provided to the neuro-oncology community, we report strong support for the integration of molecular markers into the WHO classification of brain tumors, as well as for using an integrated "layered" diagnostic format. While membership from each specialty showed support, there was variation by specialty in enthusiasm regarding proposed changes. The initial results of this survey influenced the deliberations underlying the 2016 WHO classification of tumors of the central nervous system.

  7. Human papillomavirus molecular biology.

    Science.gov (United States)

    Harden, Mallory E; Munger, Karl

    Human papillomaviruses are small DNA viruses with a tropism for squamous epithelia. A unique aspect of human papillomavirus molecular biology involves dependence on the differentiation status of the host epithelial cell to complete the viral lifecycle. A small group of these viruses are the etiologic agents of several types of human cancers, including oral and anogenital tract carcinomas. This review focuses on the basic molecular biology of human papillomaviruses. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. NeuroVault.org: A web-based repository for collecting and sharing unthresholded statistical maps of the human brain

    Directory of Open Access Journals (Sweden)

    Krzysztof Jacek Gorgolewski

    2015-04-01

    Full Text Available Here we present NeuroVault — a web based repository that allows researchers to store, share, visualize, and decode statistical maps of the human brain. NeuroVault is easy to use and employs modern web technologies to provide informative visualization of data without the need to install additional software. In addition, it leverages the power of the Neurosynth database to provide cognitive decoding of deposited maps. The data are exposed through a public REST API enabling other services and tools to take advantage of it. NeuroVault is a new resource for researchers interested in conducting meta- and coactivation analyses.

  9. [Effect of forest therapy on the human psycho-neuro-endocrino-immune network].

    Science.gov (United States)

    Li, Qing; Kawada, Tomoyuki

    2011-09-01

    Traditional thinking considered the nervous system, endocrine system and immune system to be independent of each other. However, it is now widely accepted that these systems interact through the psycho-neuro-endocrino-immune network. The nervous system affects the endocrine and immune systems by releasing neurotransmitters through the hypothalamus in the hypothalamic-pituitary portal circulation. The endocrine system affects the nervous and immune systems by secreting hormones and the immune system feeds back to the nervous and endocrine systems via cytokines. Forest therapy reduces sympathetic nervous activity, increases parasympathetic nervous activity, and regulates the balance of autonomic nerves. As a result, forest therapy decreases blood pressure and heart rate and has a relaxing effect. Forest therapy affects psychological responses via the brain and nervous system thereby decreasing the scores for anxiety, depression, anger, fatigue, and confusion, and increasing the score for vigor in the POMS test. Forest therapy acts on the endocrine system to reduce stress hormone levels such as urinary adrenaline, urinary noradrenaline, salivary cortisol, and blood cortisol levels and shows a relaxing effect. Forest therapy also acts directly and indirectly on the immune system to promote NK activity by increasing the number of NK cells and intracellular levels of anticancer proteins such as perforin, granulysin and granzymes. Taken together, forest therapy brings various effects on human health via the psycho-neuro-endocrino-immune network.

  10. Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance.

    Science.gov (United States)

    Spencer, Jeremy P E

    2008-05-01

    Emerging evidence suggests that dietary-derived flavonoids have the potential to improve human memory and neuro-cognitive performance via their ability to protect vulnerable neurons, enhance existing neuronal function and stimulate neuronal regeneration. Long-term potentiation (LTP) is widely considered to be one of the major mechanisms underlying memory acquisition, consolidation and storage in the brain and is known to be controlled at the molecular level by the activation of a number of neuronal signalling pathways. These pathways include the phosphatidylinositol-3 kinase/protein kinase B/Akt (Akt), protein kinase C, protein kinase A, Ca-calmodulin kinase and mitogen-activated protein kinase pathways. Growing evidence suggests that flavonoids exert effects on LTP, and consequently memory and cognitive performance, through their interactions with these signalling pathways. Of particular interest is the ability of flavonoids to activate the extracellular signal-regulated kinase and the Akt signalling pathways leading to the activation of the cAMP-response element-binding protein, a transcription factor responsible for increasing the expression of a number of neurotrophins important in LTP and long-term memory. One such neurotrophin is brain-derived neurotrophic factor, which is known to be crucial in controlling synapse growth, in promoting an increase in dendritic spine density and in enhancing synaptic receptor density. The present review explores the potential of flavonoids and their metabolite forms to promote memory and learning through their interactions with neuronal signalling pathways pivotal in controlling LTP and memory in human subjects.

  11. NeuroMorpho

    Data.gov (United States)

    U.S. Department of Health & Human Services — NeuroMorpho.Org is a centrally curated inventory of digitally reconstructed neurons associated with peer-reviewed publications. It contains contributions from over...

  12. Human action recognition using meta-cognitive neuro-fuzzy inference system.

    Science.gov (United States)

    Subramanian, K; Suresh, S

    2012-12-01

    We propose a sequential Meta-Cognitive learning algorithm for Neuro-Fuzzy Inference System (McFIS) to efficiently recognize human actions from video sequence. Optical flow information between two consecutive image planes can represent actions hierarchically from local pixel level to global object level, and hence are used to describe the human action in McFIS classifier. McFIS classifier and its sequential learning algorithm is developed based on the principles of self-regulation observed in human meta-cognition. McFIS decides on what-to-learn, when-to-learn and how-to-learn based on the knowledge stored in the classifier and the information contained in the new training samples. The sequential learning algorithm of McFIS is controlled and monitored by the meta-cognitive components which uses class-specific, knowledge based criteria along with self-regulatory thresholds to decide on one of the following strategies: (i) Sample deletion (ii) Sample learning and (iii) Sample reserve. Performance of proposed McFIS based human action recognition system is evaluated using benchmark Weizmann and KTH video sequences. The simulation results are compared with well known SVM classifier and also with state-of-the-art action recognition results reported in the literature. The results clearly indicates McFIS action recognition system achieves better performances with minimal computational effort.

  13. Statistical quantifiers of memory for an analysis of human brain and neuro-system diseases

    Science.gov (United States)

    Demin, S. A.; Yulmetyev, R. M.; Panischev, O. Yu.; Hänggi, Peter

    2008-03-01

    On the basis of a memory function formalism for correlation functions of time series we investigate statistical memory effects by the use of appropriate spectral and relaxation parameters of measured stochastic data for neuro-system diseases. In particular, we study the dynamics of the walk of a patient who suffers from Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and compare against the data of healthy people (CO - control group). We employ an analytical method which is able to characterize the stochastic properties of stride-to-stride variations of gait cycle timing. Our results allow us to estimate quantitatively a few human locomotion function abnormalities occurring in the human brain and in the central nervous system (CNS). Particularly, the patient's gait dynamics are characterized by an increased memory behavior together with sizable fluctuations as compared with the locomotion dynamics of healthy patients. Moreover, we complement our findings with peculiar features as detected in phase-space portraits and spectral characteristics for the different data sets (PD, HD, ALS and healthy people). The evaluation of statistical quantifiers of the memory function is shown to provide a useful toolkit which can be put to work to identify various abnormalities of locomotion dynamics. Moreover, it allows one to diagnose qualitatively and quantitatively serious brain and central nervous system diseases.

  14. Negatively-charged air conditions and responses of the human psycho-neuro-endocrino-immune network.

    Science.gov (United States)

    Takahashi, Kazuaki; Otsuki, Takemi; Mase, Akinori; Kawado, Takashi; Kotani, Muneo; Ami, Kazuhisa; Matsushima, Hiroki; Nishimura, Yasumitsu; Miura, Yoshie; Murakami, Shuko; Maeda, Megumi; Hayashi, Hiroaki; Kumagai, Naoko; Shirahama, Takashi; Yoshimatsu, Michiharu; Morimoto, Kanehisa

    2008-08-01

    Against increasing environmental adverse effects on human health such as those associated with water and ground pollution, as well as out- and indoor air conditions, trials were conducted to support and promote human health by improving the indoor air atmosphere. This study was performed to estimate the effect of negatively-charged air conditions on human biological markers related to the psycho-neuro-endocrino-immune (PNEI) network. After construction of negatively-charged experimental rooms (NCRs), healthy volunteers were admitted to these rooms and control rooms (CTRs) and various biological responses were analyzed. NCRs were constructed using a fine charcoal coating and applying an electric voltage (72 V) between the backside of walls and the ground. Various biological markers were monitored that related to general conditions, autonomic nervous systems, stress markers, immunological parameters and blood flow. Regarding the indoor environment, only negatively-charged air resulted in the difference between the CTR and NCR groups. The well-controlled experimental model-room to examine the biological effects of negatively-charged air was therefore established. Among the various parameters, IL-2, IL-4, the mean RR interval of the heart rate, and blood viscosity differed significantly between the CTR and NCR groups. In addition, the following formula was used to detect NCR-biological responses: Biological Response Value (BRV)=0.498+0.0005 [salivary cortisol]+0.072 [IL-2]+0.003 [HRM-SD]-0.013 [blood viscosity]-0.009 [blood sugar]+0.017 [pulse rate]. Negatively-charged air conditions activated the immune system slightly, smoothened blood flow and stabilized the autonomic nervous system. Although this is the first report to analyze negatively-charged air conditions on human biological responses, the long-term effects should be analyzed for the general use of these artificial atmospheres.

  15. [Neuro-neutrophilic disease suspected by human leukocyte antigen (HLA) typing and brain biopsy: a case report].

    Science.gov (United States)

    Nakanishi, Etsuro; Sawamura, Masanori; Maruhama, Shinichiro; Yamada, Hiroshi; Kim, Gan; Harada, Kiyoshi

    2015-01-01

    In a 72-year-old female, subacute right hemiplegia and aphasia appeared in late May 2011. The results of hematology, a cerebrospinal fluid test, (13)F-FDG-PET, and cephalic MRI suggested intravascular/malignant lymphoma. Brain biopsy was performed. Pathological findings did not suggest a malignant tumor. In the perivascular space, the infiltration of neutrophils or histiocytes was observed. The patient was referred to the Department of Neurology. Based on the results of various examinations, infection was ruled out, and steroid therapy was conducted. Marked improvement was achieved. Subsequently, the results of human leukocyte antigen (HLA) typing showed B54/Cw1. As dermal findings were absent, it was impossible to make a definitive diagnosis of neuro-Sweet disease, but the disorder was regarded as a neuro-neutrophilic disease, which is a more comprehensive entity. Few studies have reported brain tissue findings of active neuro-neutrophilic disease. We report the present case, which will contribute to future research.

  16. Neuro-endocrine correlations of hypothalamic-pituitary-thyroid axis in healthy humans.

    Science.gov (United States)

    Mazzoccoli, G; Carughi, S; Sperandeo, M; Pazienza, V; Giuliani, F; Tarquini, R

    2011-01-01

    Neuro-endocrine hormone secretion is characterized by circadian rhythmicity. Melatonin, GRH and GH are secreted during the night, CRH and ACTH secretion peak in the morning, determining the circadian rhythm of cortisol secretion, TRH and TSH show circadian variations with higher levels at night. Thyroxine levels do not change with clear circadian rhythmicity. In this paper we have considered a possible influence of cortisol and melatonin on hypothalamic-pituitary-thyroid axis function in humans. Melatonin, cortisol, TRH, TSH and FT4 serum levels were determined in blood samples obtained every four hours for 24 hours from ten healthy males, aged 36-51 years. We correlated hormone serum levels at each sampling time and evaluated the presence of circadian rhythmicity of hormone secretion. In the activity phase (06:00 h-10:00 h-14:00 h) cortisol correlated negatively with FT4, TSH correlated positively with TRH, TRH correlated positively with FT4 and melatonin correlated positively with TSH. In the resting phase (18:00 h-22:00 h-02:00 h) TRH correlated positively with FT4, melatonin correlated negatively with FT4, TSH correlated negatively with FT4, cortisol correlated positively with FT4 and TSH correlated positively with TRH. A clear circadian rhythm was validated for the time-qualified changes of melatonin and TSH secretion (with acrophase during the night), for cortisol serum levels (with acrophase in the morning), but not for TRH and FT4 serum level changes. In conclusion, the hypothalamic-pituitary-thyroid axis function may be modulated by cortisol and melatonin serum levels and by their circadian rhythmicity of variation.

  17. The functional neuro-anatomy of the human response to fear: A brief ...

    African Journals Online (AJOL)

    Imaging studies help to clarify the role of the amygdala-based neurocircuitry in fear activation. The aim of this paper is briefly to review the most recent functional neuro-imaging studies on fear perception, modulation and learning. Important knowledge has been acquired about the factors that set fear in motion, including the ...

  18. Neuro-epistemology: A Post-modernist Analysis of the Neuro-sciences

    African Journals Online (AJOL)

    support

    Keywords: neuro-epistemology; neuro-sciences; mental health; discourse; epistemology. ABSTRACT. This paper ... of neuro-science, including the assumptive framework upon which the dominant discourse in this field is based, which ultimately ...... human language, “attack” on Piaget's sensory-motor theory, and the focus ...

  19. Bovine herpesvirus 1 can efficiently infect the human (SH-SY5Y) but not the mouse neuroblastoma cell line (Neuro-2A).

    Science.gov (United States)

    Thunuguntla, Prasanth; El-Mayet, Fouad S; Jones, Clinton

    2017-03-15

    Bovine herpesvirus 1 (BoHV-1) is a significant bovine pathogen that establishes a life-long latent infection in sensory neurons. Previous attempts to develop immortalized bovine neuronal cells were unsuccessful. Consequently, our understanding of the BoHV-1 latency-reactivation cycle has relied on studying complex virus-host interactions in calves. In this study, we tested whether BoHV-1 can infect human (SH-SY5Y) or mouse (Neuro-2A) neuroblastoma cells. We provide new evidence that BoHV-1 efficiently infects SH-SY5Y cells and yields virus titers approximately 100 fold less than bovine kidney cells. Conversely, virus titers from productively infected Neuro-2A cells were approximately 10,000 fold less than bovine kidney cells. Using a β-Gal expressing virus (gC-Blue), we demonstrate that infection of Neuro-2A cells (actively dividing or differentiated) does not result in efficient virus spread, unlike bovine kidney or SH-SY5Y cells. Additional studies demonstrated that lytic cycle viral gene expression (bICP4 and gE) was readily detected in SH-SY5Y cells: conversely bICP4 was not readily detected in productively infected Neuro-2A cells. Finally, infection of SH-SY5Y and bovine kidney cells, but not Neuro-2A cells, led to rapid activation of the Akt protein kinase. These studies suggest that the Neuro-2A cell line may be a novel cell culture model to identify factors that regulate BoHV-1 productive infection in neuronal cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Adolescents and young adults with brain tumors in the context of molecular advances in neuro-oncology.

    Science.gov (United States)

    Zapotocky, Michal; Ramaswamy, Vijay; Lassaletta, Alvaro; Bouffet, Eric

    2018-02-01

    Adolescents and young adults (AYA) comprise a specific group of oncology patients with a distinct biological and epidemiological spectrum of central nervous system neoplasms. It has been well documented that they differ clinically, especially in relation to prognosis and chemotherapy tolerance; however, the underlying reasons for this are unclear. Recent advances in the genomics of both childhood and adult brain tumors have provided new explanations and insights into the previously described age-dependent heterogeneity. Herein, we summarize the current state of the AYA population in neuro-oncology, specifically how biological advances can help personalize therapy for this unique group of patients. © 2017 Wiley Periodicals, Inc.

  1. Quantitative structure-activity relationship analysis of human neutrophil elastase inhibitors using shuffling classification and regression trees and adaptive neuro-fuzzy inference systems.

    Science.gov (United States)

    Asadollahi-Baboli, M

    2012-07-01

    The purpose of this study was to develop quantitative structure-activity relationship models for N-benzoylindazole derivatives as inhibitors of human neutrophil elastase. These models were developed with the aid of classification and regression trees (CART) and an adaptive neuro-fuzzy inference system (ANFIS) combined with a shuffling cross-validation technique using interpretable descriptors. More than one hundred meaningful descriptors, representing various structural characteristics for all 51 N-benzoylindazole derivatives in the data set, were calculated and used as the original variables for shuffling CART modelling. Five descriptors of average Wiener index, Kier benzene-likeliness index, subpolarity parameter, average shape profile index of order 2 and folding degree index selected by the shuffling CART technique have been used as inputs of the ANFIS for prediction of inhibition behaviour of N-benzoylindazole derivatives. The results of the developed shuffling CART-ANFIS model compared to other techniques, such as genetic algorithm (GA)-partial least square (PLS)-ANFIS and stepwise multiple linear regression (MLR)-ANFIS, are promising and descriptive. The satisfactory results r2p = 0.845, Q2(LOO) = 0.861, r2(L25%O) = 0.829, RMSE(LOO)  = 0.305 and RMSE(L25%O)  = 0.336) demonstrate that shuffling CART-ANFIS models present the relationship between human neutrophil elastase inhibitor activity and molecular descriptors, and they yield predictions in excellent agreement with the experimental values.

  2. The spirituality of human consciousness: a Catholic evaluation of some current neuro-scientific interpretations.

    Science.gov (United States)

    McGoldrick, Terence A

    2012-09-01

    Catholic theology's traditional understanding of the spiritual nature of the human person begins with the idea of a rational soul and human mind that is made manifest in free will--the spiritual experience of the act of consciousness and cause of all human arts. The rationale for this religion-based idea of personhood is key to understanding ethical dilemmas posed by modern research that applies a more empirical methodology in its interpretations about the cause of human consciousness. Applications of these beliefs about the body/soul composite to the theory of evolution and to discoveries in neuroscience, paleoanthropology, as well as to recent animal intelligence studies, can be interpreted from this religious and philosophical perspective, which argues for the human soul as the unifying cause of the person's unique abilities. Free will and consciousness are at the nexus of the mutual influence of body and soul upon one another in the traditional Catholic view, that argues for a spiritual dimension to personality that is on a par with the physical metabolic processes at play. Therapies that affect consciousness are ethically problematic, because of their implications for free will and human dignity. Studies of resilience, as an example, argue for the greater, albeit limited, role of the soul's conscious choices in healing as opposed to metabolic or physical changes to the brain alone.

  3. Molecular detection of human bacterial pathogens

    National Research Council Canada - National Science Library

    Liu, Dongyou

    2011-01-01

    .... Molecular Detection of Human Bacterial Pathogens addresses this issue, with international scientists in respective bacterial pathogen research and diagnosis providing expert summaries on current...

  4. Dynamic response and transfer function of social systems: A neuro-inspired model of collective human activity patterns.

    Science.gov (United States)

    Lymperopoulos, Ilias N

    2017-10-01

    The interaction of social networks with the external environment gives rise to non-stationary activity patterns reflecting the temporal structure and strength of exogenous influences that drive social dynamical processes far from an equilibrium state. Following a neuro-inspired approach, based on the dynamics of a passive neuronal membrane, and the firing rate dynamics of single neurons and neuronal populations, we build a state-of-the-art model of the collective social response to exogenous interventions. In this regard, we analyze online activity patterns with a view to determining the transfer function of social systems, that is, the dynamic relationship between external influences and the resulting activity. To this end, first we estimate the impulse response (Green's function) of collective activity, and then we show that the convolution of the impulse response with a time-varying external influence field accurately reproduces empirical activity patterns. To capture the dynamics of collective activity when the generating process is in a state of statistical equilibrium, we incorporate into the model a noisy input convolved with the impulse response function, thus precisely reproducing the fluctuations of stationary collective activity around a resting value. The outstanding goodness-of-fit of the model results to empirical observations, indicates that the model explains human activity patterns generated by time-dependent external influences in various socio-economic contexts. The proposed model can be used for inferring the temporal structure and strength of external influences, as well as the inertia of collective social activity. Furthermore, it can potentially predict social activity patterns. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Neuro-Oncology Branch

    Science.gov (United States)

    ... BTTC are experts in their respective fields. Neuro-Oncology Clinical Fellowship This is a joint program with ... can increase survival rates. Learn more... The Neuro-Oncology Branch welcomes Dr. Mark Gilbert as new Branch ...

  6. The Origin, Development and Molecular Diversity of Rodent Olfactory Bulb Glutamatergic Neurons Distinguished by Expression of Transcription Factor NeuroD1.

    Science.gov (United States)

    Roybon, Laurent; Mastracci, Teresa L; Li, Joyce; Stott, Simon R W; Leiter, Andrew B; Sussel, Lori; Brundin, Patrik; Li, Jia-Yi

    2015-01-01

    Production of olfactory bulb neurons occurs continuously in the rodent brain. Little is known, however, about cellular diversity in the glutamatergic neuron subpopulation. In the central nervous system, the basic helix-loop-helix transcription factor NeuroD1 (ND1) is commonly associated with glutamatergic neuron development. In this study, we utilized ND1 to identify the different subpopulations of olfactory bulb glutamategic neurons and their progenitors, both in the embryo and postnatally. Using knock-in mice, transgenic mice and retroviral transgene delivery, we demonstrate the existence of several different populations of glutamatergic olfactory bulb neurons, the progenitors of which are ND1+ and ND1- lineage-restricted, and are temporally and regionally separated. We show that the first olfactory bulb glutamatergic neurons produced - the mitral cells - can be divided into molecularly diverse subpopulations. Our findings illustrate the complexity of neuronal diversity in the olfactory bulb and that seemingly homogenous neuronal populations can consist of multiple subpopulations with unique molecular signatures of transcription factors and expressing neuronal subtype-specific markers.

  7. The Origin, Development and Molecular Diversity of Rodent Olfactory Bulb Glutamatergic Neurons Distinguished by Expression of Transcription Factor NeuroD1.

    Directory of Open Access Journals (Sweden)

    Laurent Roybon

    Full Text Available Production of olfactory bulb neurons occurs continuously in the rodent brain. Little is known, however, about cellular diversity in the glutamatergic neuron subpopulation. In the central nervous system, the basic helix-loop-helix transcription factor NeuroD1 (ND1 is commonly associated with glutamatergic neuron development. In this study, we utilized ND1 to identify the different subpopulations of olfactory bulb glutamategic neurons and their progenitors, both in the embryo and postnatally. Using knock-in mice, transgenic mice and retroviral transgene delivery, we demonstrate the existence of several different populations of glutamatergic olfactory bulb neurons, the progenitors of which are ND1+ and ND1- lineage-restricted, and are temporally and regionally separated. We show that the first olfactory bulb glutamatergic neurons produced - the mitral cells - can be divided into molecularly diverse subpopulations. Our findings illustrate the complexity of neuronal diversity in the olfactory bulb and that seemingly homogenous neuronal populations can consist of multiple subpopulations with unique molecular signatures of transcription factors and expressing neuronal subtype-specific markers.

  8. From neuro-functional to neuro-computational models. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

    Science.gov (United States)

    Briesemeister, Benny B.

    2015-06-01

    Historically, there has been a strong opposition between psychological theories of human emotion that suggest a limited number of distinct functional categories, such as anger, fear, happiness and so forth (e.g. [1]), and theories that suggest processing along affective dimensions, such as valence and arousal (e.g. [2]). Only few current models acknowledge that both of these perspectives seem to be legitimate [3], and at their core, even fewer models connect these insights with knowledge about neurophysiology [4]. In this regard, the Quartet Theory of Human Emotions (QTHE) [5] makes a very important and useful contribution to the field of emotion research - but in my opinion, there is still at least one more step to go.

  9. The functional neuro-anatomy of the human response to fear: A brief review

    Directory of Open Access Journals (Sweden)

    A Del Casale

    2011-03-01

    Full Text Available The perception of fear and subsequent appropriate behavioral responding are crucial for the adaptation of species to their living environment. Functional neuroimaging studies of the neural basis of fear during the last few decades in humans contributed to significant advancement in the understanding of its mechanisms. Imaging studies help us delineating the role of amygdala-based neurocircuitry in fear activation and attention capture. The aim of this paper was to briefly review the most recent functional neuroimaging studies of fear perception, modulation and learning. Important knowledge was acquired about the factors that set fear in motion, including the role of nonconscious processes and the character of fear in guiding attention. A subcortical network interacts with the prefrontal cortex to modulate emotional response that allows better coping with environmental and social circumstances. Fear learning reduces the need to relearn about danger, and flexibility processes readjust fear behavior when external circumstances change. Future improvement of functional and other neuroimaging techniques may promote better clarification of the neurocircuitry involved in fear perception, learning and modulation.

  10. The evolution of neuroArm.

    Science.gov (United States)

    Sutherland, Garnette R; Wolfsberger, Stefan; Lama, Sanju; Zarei-nia, Kourosh

    2013-01-01

    Intraoperative imaging disrupts the rhythm of surgery despite providing an excellent opportunity for surgical monitoring and assessment. To allow surgery within real-time images, neuroArm, a teleoperated surgical robotic system, was conceptualized. The objective was to design and manufacture a magnetic resonance-compatible robot with a human-machine interface that could reproduce some of the sight, sound, and touch of surgery at a remote workstation. University of Calgary researchers worked with MacDonald, Dettwiler and Associates engineers to produce a requirements document, preliminary design review, and critical design review, followed by the manufacture, preclinical testing, and clinical integration of neuroArm. During the preliminary design review, the scope of the neuroArm project changed to performing microsurgery outside the magnet and stereotaxy inside the bore. neuroArm was successfully manufactured and installed in an intraoperative magnetic resonance imaging operating room. neuroArm was clinically integrated into 35 cases in a graded fashion. As a result of this experience, neuroArm II is in development, and advances in technology will allow microsurgery within the bore of the magnet. neuroArm represents a successful interdisciplinary collaboration. It has positive implications for the future of robotic technology in neurosurgery in that the precision and accuracy of robots will continue to augment human capability.

  11. Molecular evolution of human species D adenoviruses.

    Science.gov (United States)

    Robinson, Christopher M; Seto, Donald; Jones, Morris S; Dyer, David W; Chodosh, James

    2011-08-01

    Adenoviruses are medium-sized double stranded DNA viruses that infect vertebrates. Human adenoviruses cause an array of diseases. Currently there are 56 human adenovirus types recognized and characterized within seven species (A-G). Of those types, a majority belongs to species D. In this review, the genomic conservation and diversity are examined among human adenoviruses within species D, particularly in contrast to other human adenovirus species. Specifically, homologous recombination is presented as a driving force for the molecular evolution of human adenoviruses and the emergence of new adenovirus pathogens. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. The Molecular Basis of Human Brain Evolution.

    Science.gov (United States)

    Enard, Wolfgang

    2016-10-24

    Humans are a remarkable species, especially because of the remarkable properties of their brain. Since the split from the chimpanzee lineage, the human brain has increased three-fold in size and has acquired abilities for vocal learning, language and intense cooperation. To better understand the molecular basis of these changes is of great biological and biomedical interest. However, all the about 16 million fixed genetic changes that occurred during human evolution are fully correlated with all molecular, cellular, anatomical and behavioral changes that occurred during this time. Hence, as humans and chimpanzees cannot be crossed or genetically manipulated, no direct evidence for linking particular genetic and molecular changes to human brain evolution can be obtained. Here, I sketch a framework how indirect evidence can be obtained and review findings related to the molecular basis of human cognition, vocal learning and brain size. In particular, I discuss how a comprehensive comparative approach, leveraging cellular systems and genomic technologies, could inform the evolution of our brain in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Computer Simulation Study of Human Locomotion with a Three-Dimensional Entire-Body Neuro-Musculo-Skeletal Model

    Science.gov (United States)

    Hase, Kazunori; Yokoi, Takashi

    In the present study, the computer simulation technique to autonomously generate running motion from walking was developed using a three-dimensional entire-body neuro-musculo-skeletal model. When maximizing locomotive speed was employed as the evaluative criterion, the initial walking pattern could not transition to a valid running motion. When minimizing the period of foot-ground contact was added to this evaluative criterion, the simulation model autonomously produced appropriate three-dimensional running. Changes in the neuronal system showed the fatigue coefficient of the neural oscillators to reduce as locomotion patterns transitioned from walking to running. Then, when the running speed increased, the amplitude of the non-specific stimulus from the higher center increased. These two changes indicate mean that the improvement in responsiveness of the neuronal system is important for the transition process from walking to running, and that the comprehensive activation level of the neuronal system is essential in the process of increasing running speed.

  14. Molecular Anatomy of the Developing Human Retina.

    Science.gov (United States)

    Hoshino, Akina; Ratnapriya, Rinki; Brooks, Matthew J; Chaitankar, Vijender; Wilken, Matthew S; Zhang, Chi; Starostik, Margaret R; Gieser, Linn; La Torre, Anna; Nishio, Mario; Bates, Olivia; Walton, Ashley; Bermingham-McDonogh, Olivia; Glass, Ian A; Wong, Rachel O L; Swaroop, Anand; Reh, Thomas A

    2017-12-18

    Clinical and genetic heterogeneity associated with retinal diseases makes stem-cell-based therapies an attractive strategy for personalized medicine. However, we have limited understanding of the timing of key events in the developing human retina, and in particular the factors critical for generating the unique architecture of the fovea and surrounding macula. Here we define three key epochs in the transcriptome dynamics of human retina from fetal day (D) 52 to 136. Coincident histological analyses confirmed the cellular basis of transcriptional changes and highlighted the dramatic acceleration of development in the fovea compared with peripheral retina. Human and mouse retinal transcriptomes show remarkable similarity in developmental stages, although morphogenesis was greatly expanded in humans. Integration of DNA accessibility data allowed us to reconstruct transcriptional networks controlling photoreceptor differentiation. Our studies provide insights into human retinal development and serve as a resource for molecular staging of human stem-cell-derived retinal organoids. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Neuro-oxidative-nitrosative stress in sepsis

    DEFF Research Database (Denmark)

    Berg, Ronan M G; Møller, Kirsten; Bailey, Damian M

    2011-01-01

    Neuro-oxidative-nitrosative stress may prove the molecular basis underlying brain dysfunction in sepsis. In the current review, we describe how sepsis-induced reactive oxygen and nitrogen species (ROS/RNS) trigger lipid peroxidation chain reactions throughout the cerebrovasculature and surrounding...

  16. Molecular biology of the human brain

    Energy Technology Data Exchange (ETDEWEB)

    Jones, E.G.

    1988-01-01

    This book examines new methods of molecular biology that are providing valuable insights into the human brain, the genes that govern its assembly and function, and the many genetic defects that cause neurological diseases such as Alzheimer's, Cri du Chat syndrome, Huntington's disease, and bipolar depression disorder. In addition, the book reviews techniques in molecular neurobiological research, including the use of affinity reagents, chimeric receptors, and site-directed mutagenesis in localizing the ion channel and cholinergic binding site, and the application of somatic cell genetics in isolating specific chromosomes or chromosomal segments.

  17. The UC Davis/NIH NeuroMab Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The mission of the UC Davis/NIH NeuroMab facility is to generate and distribute high quality, validated mouse monoclonal antibodies against molecular targets found...

  18. Molecular Structure of Human-Liver Glycogen.

    Directory of Open Access Journals (Sweden)

    Bin Deng

    Full Text Available Glycogen is a highly branched glucose polymer which is involved in maintaining blood-sugar homeostasis. Liver glycogen contains large composite α particles made up of linked β particles. Previous studies have shown that the binding which links β particles into α particles is impaired in diabetic mice. The present study reports the first molecular structural characterization of human-liver glycogen from non-diabetic patients, using transmission electron microscopy for morphology and size-exclusion chromatography for the molecular size distribution; the latter is also studied as a function of time during acid hydrolysis in vitro, which is sensitive to certain structural features, particularly glycosidic vs. proteinaceous linkages. The results are compared with those seen in mice and pigs. The molecular structural change during acid hydrolysis is similar in each case, and indicates that the linkage of β into α particles is not glycosidic. This result, and the similar morphology in each case, together imply that human liver glycogen has similar molecular structure to those of mice and pigs. This knowledge will be useful for future diabetes drug targets.

  19. Molecular Adaptation of Modern Human Populations

    Directory of Open Access Journals (Sweden)

    Hong Shi

    2011-01-01

    Full Text Available Modern humans have gone through varied processes of genetic adaptations when their ancestors left Africa about 100,000 years ago. The environmental stresses and the social transitions (e.g., emergence of the Neolithic culture have been acting as the major selective forces reshaping the genetic make-up of human populations. Genetic adaptations have occurred in many aspects of human life, including the adaptation to cold climate and high-altitude hypoxia, the improved ability of defending infectious diseases, and the polished strategy of utilizing new diet with the advent of agriculture. At the same time, the adaptations once developed during evolution may sometimes generate deleterious effects (e.g., susceptibility to diseases when facing new environmental and social changes. The molecular (especially the genome-wide screening of genetic variations studies in recent years have detected many genetic variants that show signals of Darwinian positive selection in modern human populations, which will not only provide a better understanding of human evolutionary history, but also help dissecting the genetic basis of human complex diseases.

  20. NeuroQuiz

    DEFF Research Database (Denmark)

    Brent, Mikkel Bo; Emmanuel, Thomas

    2016-01-01

    NeuroQuiz er en quiz-app udviklet til neuroanatomi. Den består af mere end 1500 spørgsmål og over 350 anatomiske billeder. Alle spørgsmål tager udgangspunkt i lærebogen Neuroanatomi af Carsten Reidies Bjarkam.......NeuroQuiz er en quiz-app udviklet til neuroanatomi. Den består af mere end 1500 spørgsmål og over 350 anatomiske billeder. Alle spørgsmål tager udgangspunkt i lærebogen Neuroanatomi af Carsten Reidies Bjarkam....

  1. NeuroAIDS in Africa.

    Science.gov (United States)

    Robertson, Kevin; Liner, Jeff; Hakim, James; Sankalé, Jean-Louis; Grant, Igor; Letendre, Scott; Clifford, David; Diop, Amadou Gallo; Jaye, Assan; Kanmogne, Georgette; Njamnshi, Alfred; Langford, T Dianne; Weyessa, Tufa Gemechu; Wood, Charles; Banda, Mwanza; Hosseinipour, Mina; Sacktor, Ned; Nakasuja, Noeline; Bangirana, Paul; Paul, Robert; Joska, John; Wong, Joseph; Boivin, Michael; Holding, Penny; Kammerer, Betsy; Van Rie, Annelies; Ive, Prudence; Nath, Avindra; Lawler, Kathy; Adebamowo, Clement; Royal, Walter; Joseph, Jeymohan

    2010-05-01

    In July 2009, the Center for Mental Health Research on AIDS at the National Institute of Mental Health organized and supported the meeting "NeuroAIDS in Africa." This meeting was held in Cape Town, South Africa, and was affiliated with the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Presentations began with an overview of the epidemiology of HIV in sub-Saharan Africa, the molecular epidemiology of HIV, HIV-associated neurocognitive disorders (HANDs), and HAND treatment. These introductory talks were followed by presentations on HAND research and clinical care in Botswana, Cameroon, Ethiopia, The Gambia, Kenya, Malawi, Nigeria, Senegal, South Africa, Uganda, and Zambia. Topics discussed included best practices for assessing neurocognitive disorders, patterns of central nervous system (CNS) involvement in the region, subtype-associated risk for HAND, pediatric HIV assessments and neurodevelopment, HIV-associated CNS opportunistic infections and immune reconstitution syndrome, the evolving changes in treatment implementation, and various opportunities and strategies for NeuroAIDS research and capacity building in the region.

  2. Molecular basis of human cerebral malaria development.

    Science.gov (United States)

    Wah, Saw Thu; Hananantachai, Hathairad; Kerdpin, Usanee; Plabplueng, Chotiros; Prachayasittikul, Virapong; Nuchnoi, Pornlada

    2016-01-01

    Cerebral malaria is still a deleterious health problem in tropical countries. The wide spread of malarial drug resistance and the lack of an effective vaccine are obstacles for disease management and prevention. Parasite and human genetic factors play important roles in malaria susceptibility and disease severity. The malaria parasite exerted a potent selective signature on the human genome, which is apparent in the genetic polymorphism landscape of genes related to pathogenesis. Currently, much genomic data and a novel body of knowledge, including the identification of microRNAs, are being increasingly accumulated for the development of laboratory testing cassettes for cerebral malaria prevention. Therefore, understanding of the underlying complex molecular basis of cerebral malaria is important for the design of strategy for cerebral malaria treatment and control.

  3. Merging machines with microsurgery: clinical experience with neuroArm.

    Science.gov (United States)

    Sutherland, Garnette R; Lama, Sanju; Gan, Liu Shi; Wolfsberger, Stefan; Zareinia, Kourosh

    2013-03-01

    It has been over a decade since the introduction of the da Vinci Surgical System into surgery. Since then, technology has been advancing at an exponential rate, and newer surgical robots are becoming increasingly sophisticated, which could greatly impact the performance of surgery. NeuroArm is one such robotic system. Clinical integration of neuroArm, an MR-compatible image-guided robot, into surgical procedure has been developed over a prospective series of 35 cases with varying pathology. Only 1 adverse event was encountered in the first 35 neuroArm cases, with no patient injury. The adverse event was uncontrolled motion of the left neuroArm manipulator, which was corrected through a rigorous safety review procedure. Surgeons used a graded approach to introducing neuroArm into surgery, with routine dissection of the tumor-brain interface occurring over the last 15 cases. The use of neuroArm for routine dissection shows that robotic technology can be successfully integrated into microsurgery. Karnofsky performance status scores were significantly improved postoperatively and at 12-week follow-up. Surgical robots have the potential to improve surgical precision and accuracy through motion scaling and tremor filters, although human surgeons currently possess superior speed and dexterity. Additionally, neuroArm's workstation has positive implications for technology management and surgical education. NeuroArm is a step toward a future in which a variety of machines are merged with medicine.

  4. Modeling cortisol dynamics in the neuro-endocrine axis distinguishes normal, depression, and post-traumatic stress disorder (PTSD in humans.

    Directory of Open Access Journals (Sweden)

    K Sriram

    Full Text Available Cortisol, secreted in the adrenal cortex in response to stress, is an informative biomarker that distinguishes anxiety disorders such as major depression and post-traumatic stress disorder (PTSD from normal subjects. Yehuda et al. proposed a hypothesis that, in humans, the hypersensitive hypothalamus-pituitary-adrenal (HPA axis is responsible for the occurrence of differing levels of cortisol in anxiety disorders. Specifically, PTSD subjects have lower cortisol levels during the late subjective night in comparison to normal subjects, and this was assumed to occur due to strong negative feedback loops in the HPA axis. In the present work, to address this hypothesis, we modeled the cortisol dynamics using nonlinear ordinary differential equations and estimated the kinetic parameters of the model to fit the experimental data of three categories, namely, normal, depressed, and PTSD human subjects. We concatenated the subjects (n = 3 in each category and created a model subject (n = 1 without considering the patient-to-patient variability in each case. The parameters of the model for the three categories were simultaneously obtained through global optimization. Bifurcation analysis carried out with the optimized parameters exhibited two supercritical Hopf points and, for the choice of parameters, the oscillations were found to be circadian in nature. The fitted kinetic parameters indicate that PTSD subjects have a strong negative feedback loop and, as a result, the predicted oscillating cortisol levels are extremely low at the nadir in contrast to normal subjects, albeit within the endocrinologic range. We also simulated the phenotypes for each of the categories and, as observed in the clinical data of PTSD patients, the simulated cortisol levels are consistently low at the nadir, and correspondingly the negative feedback was found to be extremely strong. These results from the model support the hypothesis that high stress intensity and

  5. Human development I: Twenty Fundamental Problems of Biology, Medicine, and Neuro-Psychology Related to Biological Information

    Directory of Open Access Journals (Sweden)

    Tyge Dahl Hermansen

    2006-01-01

    Full Text Available In a new series of papers, we address a number of unsolved problems in biology today. First of all, the unsolved enigma concerning how the differentiation from a single zygote to an adult individual happens has been object for severe research for decades. By uncovering a new holistic biological paradigm that introduces an energetic-informational interpretation of reality as a new way to experience biology, these papers will try to solve the problems connected with the events of biological ontogenesis involving a fractal hierarchy, from a single cell to the function of the human brain. The problems discussed are interpreted within the frames of a universe of roomy fractal structures containing energetic patterns that are able to deliver biological information. We think biological organization is guided by energetic changes on the level of quantum mechanics, interacting with the intention that again guides the energetic conformation of the fractal structures to gain disorders or healthiness. Furthermore, we introduce two new concepts: “metamorphous top down” evolution and “adult human metamorphosis”. The first is a new evolutionary theory involving metamorphosis as a main concept of evolution. The last is tightly linked to the evolutionary principle and explains how human self-recovery is governed. Other subjects of special interest that we shall look deeper into are the immunological self-nonself discrimination, the structure and function of the human brain, the etiology and salutogenesis of mental and somatic diseases, and the structure of the consciousness of a human being. We shall criticize Szentagothai’s model for the modulated structure of the human cerebral cortex and Jerne’s theory of the immunological regulatory anti-idiotypic network.

  6. Human development I: twenty fundamental problems of biology, medicine, and neuro-psychology related to biological information.

    Science.gov (United States)

    Hermansen, Tyge Dahl; Ventegodt, Søren; Rald, Erik; Clausen, Birgitte; Nielsen, Maj Lyck; Merrick, Joav

    2006-07-06

    In a new series of papers, we address a number of unsolved problems in biology today. First of all, the unsolved enigma concerning how the differentiation from a single zygote to an adult individual happens has been object for severe research for decades. By uncovering a new holistic biological paradigm that introduces an energetic-informational interpretation of reality as a new way to experience biology, these papers will try to solve the problems connected with the events of biological ontogenesis involving a fractal hierarchy, from a single cell to the function of the human brain. The problems discussed are interpreted within the frames of a universe of roomy fractal structures containing energetic patterns that are able to deliver biological information. We think biological organization is guided by energetic changes on the level of quantum mechanics, interacting with the intention that again guides the energetic conformation of the fractal structures to gain disorders or healthiness. Furthermore, we introduce two new concepts: "metamorphous top down" evolution and "adult human metamorphosis". The first is a new evolutionary theory involving metamorphosis as a main concept of evolution. The last is tightly linked to the evolutionary principle and explains how human self-recovery is governed. Other subjects of special interest that we shall look deeper into are the immunological self-nonself discrimination, the structure and function of the human brain, the etiology and salutogenesis of mental and somatic diseases, and the structure of the consciousness of a human being. We shall criticize Szentagothai's model for the modulated structure of the human cerebral cortex and Jerne's theory of the immunological regulatory anti-idiotypic network.

  7. Human papilloma virus (HPV) molecular diagnostics.

    Science.gov (United States)

    Kroupis, Christos; Vourlidis, Nikolaos

    2011-11-01

    Human Papilloma Virus (HPV) is becoming a menace worldwide, especially to the developing world, due to its involvement in a variety of malignancies, with cervical cancer being the most important and prevalent. There are many HPV types; HPV 16/18 are the most carcinogenic but few others are also characterized as high-risk (HR). They can cause a variety of low- or high-grade cellular abnormalities, most frequently detected in a routine Pap test. Most infections clear within 2 years, however, a minority persists and potentially could progress to cervical cancer. Molecular tests detecting HPV DNA, RNA or proteins are now being available either commercially or in-house developed. DNA detection is nowadays an established tool for diagnosis and monitoring of HPV-related disease, however, there is lack of a reference method and standardization with reference materials. The various available test formats create confusion on which molecular test to choose and what are its limitations. Therefore, the need for lab accreditation and participation in proficiency testing has to be stressed. Novel HPV biomarkers (RNA, protein etc.) are now intensively examined for their inclusion as adjunct tools. Recently, developed prophylactic vaccines for HPV 16/18 have already proven safe and efficient and raise high expectations for the complete eradication of these types in the future.

  8. The Affective Core of the Self: A Neuro-Archetypical Perspective on the Foundations of Human (and Animal) Subjectivity

    OpenAIRE

    Alcaro, Antonio; Carta, Stefano; Panksepp, Jaak

    2017-01-01

    Psychologists usually considered the “Self” as an object of experience appearing when the individual perceives its existence within the conscious field. In accordance with such a view, the self-representing capacity of the human mind has been related to corticolimbic learning processes taking place within individual development. On the other hand, Carl Gustav Jung considered the Self as the core of our personality, in its conscious and unconscious aspects, as well as in its actual and potenti...

  9. The Affective Core of the Self: A Neuro-Archetypical Perspective on the Foundations of Human (and Animal) Subjectivity.

    Science.gov (United States)

    Alcaro, Antonio; Carta, Stefano; Panksepp, Jaak

    2017-01-01

    Psychologists usually considered the "Self" as an object of experience appearing when the individual perceives its existence within the conscious field. In accordance with such a view, the self-representing capacity of the human mind has been related to corticolimbic learning processes taking place within individual development. On the other hand, Carl Gustav Jung considered the Self as the core of our personality, in its conscious and unconscious aspects, as well as in its actual and potential forms. According to Jung, the Self originates from an inborn dynamic structure integrating the essential drives of our "brain-mind," and leading both to instinctual behavioral actions and to archetypal psychological experiences. Interestingly, recent neuroethological studies indicate that our subjective identity rests on ancient neuropsychic processes that humans share with other animals as part of their inborn constitutional repertoire. Indeed, brain activity within subcortical midline structures (SCMSs) is intrinsically related to the emergence of prototypical affective states, that not only influence our behavior in a flexible way, but alter our conscious field, giving rise to specific feelings or moods, which constitute the first form of self-orientation in the world. Moreover, such affective dynamics play a central role in the organization of individual personality and in the evolution of all other (more sophisticated) psychological functions. Therefore, on the base of the convergence between contemporary cutting-edge scientific research and some psychological intuitions of Jung, we intend here to explore the first neuroevolutional layer of human mind, that we call the affective core of the Self.

  10. Chaotic Neuro-Computer

    Science.gov (United States)

    Horio, Yoshihiko; Aihara, Kazuyuki

    This chapter describes mixed analog/digital circuit implementations of a chaotic neuro-computer system. The chaotic neuron model is implemented with a switched-capacitor (SC) integrated circuit technique. The analog SC circuit can handle real numbers electrically in the sense that the state variables of the analog circuits are continuous. Therefore, chaotic dynamics can be faithfully replicated with the SC chaotic neuron circuit. The synaptic connections, on the other hand, are realized with digital circuits to accommodate a vast number of synapses. We propose a memory-based digital synapse circuit architecture that draws upon the table look-up method to achieve rapid calculation of a large number of weighted summations. The first generation chaotic neuro-computer with 16 SC neurons and 256 synapses is reviewed. Finally, a large-scale system with 10000 neurons and 100002 synapses is described.

  11. The Affective Core of the Self: A Neuro-Archetypical Perspective on the Foundations of Human (and Animal Subjectivity

    Directory of Open Access Journals (Sweden)

    Antonio Alcaro

    2017-09-01

    Full Text Available Psychologists usually considered the “Self” as an object of experience appearing when the individual perceives its existence within the conscious field. In accordance with such a view, the self-representing capacity of the human mind has been related to corticolimbic learning processes taking place within individual development. On the other hand, Carl Gustav Jung considered the Self as the core of our personality, in its conscious and unconscious aspects, as well as in its actual and potential forms. According to Jung, the Self originates from an inborn dynamic structure integrating the essential drives of our “brain–mind,” and leading both to instinctual behavioral actions and to archetypal psychological experiences. Interestingly, recent neuroethological studies indicate that our subjective identity rests on ancient neuropsychic processes that humans share with other animals as part of their inborn constitutional repertoire. Indeed, brain activity within subcortical midline structures (SCMSs is intrinsically related to the emergence of prototypical affective states, that not only influence our behavior in a flexible way, but alter our conscious field, giving rise to specific feelings or moods, which constitute the first form of self-orientation in the world. Moreover, such affective dynamics play a central role in the organization of individual personality and in the evolution of all other (more sophisticated psychological functions. Therefore, on the base of the convergence between contemporary cutting-edge scientific research and some psychological intuitions of Jung, we intend here to explore the first neuroevolutional layer of human mind, that we call the affective core of the Self.

  12. The Affective Core of the Self: A Neuro-Archetypical Perspective on the Foundations of Human (and Animal) Subjectivity

    Science.gov (United States)

    Alcaro, Antonio; Carta, Stefano; Panksepp, Jaak

    2017-01-01

    Psychologists usually considered the “Self” as an object of experience appearing when the individual perceives its existence within the conscious field. In accordance with such a view, the self-representing capacity of the human mind has been related to corticolimbic learning processes taking place within individual development. On the other hand, Carl Gustav Jung considered the Self as the core of our personality, in its conscious and unconscious aspects, as well as in its actual and potential forms. According to Jung, the Self originates from an inborn dynamic structure integrating the essential drives of our “brain–mind,” and leading both to instinctual behavioral actions and to archetypal psychological experiences. Interestingly, recent neuroethological studies indicate that our subjective identity rests on ancient neuropsychic processes that humans share with other animals as part of their inborn constitutional repertoire. Indeed, brain activity within subcortical midline structures (SCMSs) is intrinsically related to the emergence of prototypical affective states, that not only influence our behavior in a flexible way, but alter our conscious field, giving rise to specific feelings or moods, which constitute the first form of self-orientation in the world. Moreover, such affective dynamics play a central role in the organization of individual personality and in the evolution of all other (more sophisticated) psychological functions. Therefore, on the base of the convergence between contemporary cutting-edge scientific research and some psychological intuitions of Jung, we intend here to explore the first neuroevolutional layer of human mind, that we call the affective core of the Self. PMID:28919868

  13. Common gene-network signature of different neurological disorders and their potential implications to neuroAIDS.

    Directory of Open Access Journals (Sweden)

    Vidya Sagar

    Full Text Available The neurological complications of AIDS (neuroAIDS during the infection of human immunodeficiency virus (HIV are symptomized by non-specific, multifaceted neurological conditions and therefore, defining a specific diagnosis/treatment mechanism(s for this neuro-complexity at the molecular level remains elusive. Using an in silico based integrated gene network analysis we discovered that HIV infection shares convergent gene networks with each of twelve neurological disorders selected in this study. Importantly, a common gene network was identified among HIV infection, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and age macular degeneration. An mRNA microarray analysis in HIV-infected monocytes showed significant changes in the expression of several genes of this in silico derived common pathway which suggests the possible physiological relevance of this gene-circuit in driving neuroAIDS condition. Further, this unique gene network was compared with another in silico derived novel, convergent gene network which is shared by seven major neurological disorders (Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Age Macular Degeneration, Amyotrophic Lateral Sclerosis, Vascular Dementia, and Restless Leg Syndrome. These networks differed in their gene circuits; however, in large, they involved innate immunity signaling pathways, which suggests commonalities in the immunological basis of different neuropathogenesis. The common gene circuits reported here can provide a prospective platform to understand how gene-circuits belonging to other neuro-disorders may be convoluted during real-time neuroAIDS condition and it may elucidate the underlying-and so far unknown-genetic overlap between HIV infection and neuroAIDS risk. Also, it may lead to a new paradigm in understanding disease progression, identifying biomarkers, and developing therapies.

  14. Frequency and Pathological Phenotype of Bovine Astrovirus CH13/NeuroS1 Infection in Neurologically-Diseased Cattle: Towards Assessment of Causality.

    Science.gov (United States)

    Selimovic-Hamza, Senija; Boujon, Céline L; Hilbe, Monika; Oevermann, Anna; Seuberlich, Torsten

    2017-01-18

    Next-generation sequencing (NGS) has opened up the possibility of detecting new viruses in unresolved diseases. Recently, astrovirus brain infections have been identified in neurologically diseased humans and animals by NGS, among them bovine astrovirus (BoAstV) CH13/NeuroS1, which has been found in brain tissues of cattle with non-suppurative encephalitis. Only a few studies are available on neurotropic astroviruses and a causal relationship between BoAstV CH13/NeuroS1 infections and neurological disease has been postulated, but remains unproven. Aiming at making a step forward towards assessing the causality, we collected brain samples of 97 cases of cattle diagnosed with unresolved non-suppurative encephalitis, and analyzed them by in situ hybridization and immunohistochemistry, to determine the frequency and neuropathological distribution of the BoAstV CH13/NeuroS1 and its topographical correlation to the pathology. We detected BoAstV CH13/NeuroS1 RNA or proteins in neurons throughout all parts of the central nervous system (CNS) in 34% of all cases, but none were detected in cattle of the control group. In general, brain lesions had a high correlation with the presence of the virus. These findings show that a substantial proportion of cattle with non-suppurative encephalitis are infected with BoAstV CH13/NeuroS1 and further substantiate the causal relationship between neurological disease and astrovirus infections.

  15. Frequency and Pathological Phenotype of Bovine Astrovirus CH13/NeuroS1 Infection in Neurologically-Diseased Cattle: Towards Assessment of Causality

    Directory of Open Access Journals (Sweden)

    Senija Selimovic-Hamza

    2017-01-01

    Full Text Available Next-generation sequencing (NGS has opened up the possibility of detecting new viruses in unresolved diseases. Recently, astrovirus brain infections have been identified in neurologically diseased humans and animals by NGS, among them bovine astrovirus (BoAstV CH13/NeuroS1, which has been found in brain tissues of cattle with non-suppurative encephalitis. Only a few studies are available on neurotropic astroviruses and a causal relationship between BoAstV CH13/NeuroS1 infections and neurological disease has been postulated, but remains unproven. Aiming at making a step forward towards assessing the causality, we collected brain samples of 97 cases of cattle diagnosed with unresolved non-suppurative encephalitis, and analyzed them by in situ hybridization and immunohistochemistry, to determine the frequency and neuropathological distribution of the BoAstV CH13/NeuroS1 and its topographical correlation to the pathology. We detected BoAstV CH13/NeuroS1 RNA or proteins in neurons throughout all parts of the central nervous system (CNS in 34% of all cases, but none were detected in cattle of the control group. In general, brain lesions had a high correlation with the presence of the virus. These findings show that a substantial proportion of cattle with non-suppurative encephalitis are infected with BoAstV CH13/NeuroS1 and further substantiate the causal relationship between neurological disease and astrovirus infections.

  16. Frequency and Pathological Phenotype of Bovine Astrovirus CH13/NeuroS1 Infection in Neurologically-Diseased Cattle: Towards Assessment of Causality

    Science.gov (United States)

    Selimovic-Hamza, Senija; Boujon, Céline L.; Hilbe, Monika; Oevermann, Anna; Seuberlich, Torsten

    2017-01-01

    Next-generation sequencing (NGS) has opened up the possibility of detecting new viruses in unresolved diseases. Recently, astrovirus brain infections have been identified in neurologically diseased humans and animals by NGS, among them bovine astrovirus (BoAstV) CH13/NeuroS1, which has been found in brain tissues of cattle with non-suppurative encephalitis. Only a few studies are available on neurotropic astroviruses and a causal relationship between BoAstV CH13/NeuroS1 infections and neurological disease has been postulated, but remains unproven. Aiming at making a step forward towards assessing the causality, we collected brain samples of 97 cases of cattle diagnosed with unresolved non-suppurative encephalitis, and analyzed them by in situ hybridization and immunohistochemistry, to determine the frequency and neuropathological distribution of the BoAstV CH13/NeuroS1 and its topographical correlation to the pathology. We detected BoAstV CH13/NeuroS1 RNA or proteins in neurons throughout all parts of the central nervous system (CNS) in 34% of all cases, but none were detected in cattle of the control group. In general, brain lesions had a high correlation with the presence of the virus. These findings show that a substantial proportion of cattle with non-suppurative encephalitis are infected with BoAstV CH13/NeuroS1 and further substantiate the causal relationship between neurological disease and astrovirus infections. PMID:28106800

  17. Neuro-Epigenetic Indications of Acute Stress Response in Humans: The Case of MicroRNA-29c.

    Directory of Open Access Journals (Sweden)

    Sharon Vaisvaser

    Full Text Available Stress research has progressively become more integrative in nature, seeking to unfold crucial relations between the different phenotypic levels of stress manifestations. This study sought to unravel stress-induced variations in expression of human microRNAs sampled in peripheral blood mononuclear cells and further assess their relationship with neuronal and psychological indices. We obtained blood samples from 49 healthy male participants before and three hours after performing a social stress task, while undergoing functional magnetic resonance imaging (fMRI. A seed-based functional connectivity (FC analysis was conducted for the ventro-medial prefrontal cortex (vmPFC, a key area of stress regulation. Out of hundreds of microRNAs, a specific increase was identified in microRNA-29c (miR-29c expression, corresponding with both the experience of sustained stress via self-reports, and alterations in vmPFC functional connectivity. Explicitly, miR-29c expression levels corresponded with both increased connectivity of the vmPFC with the anterior insula (aIns, and decreased connectivity of the vmPFC with the left dorso-lateral prefrontal cortex (dlPFC. Our findings further revealed that miR-29c mediates an indirect path linking enhanced vmPFC-aIns connectivity during stress with subsequent experiences of sustained stress. The correlative patterns of miR-29c expression and vmPFC FC, along with the mediating effects on subjective stress sustainment and the presumed localization of miR-29c in astrocytes, together point to an intriguing assumption; miR-29c may serve as a biomarker in the blood for stress-induced functional neural alterations reflecting regulatory processes. Such a multi-level model may hold the key for future personalized intervention in stress psychopathology.

  18. The contribution of CXCL12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development

    Directory of Open Access Journals (Sweden)

    Mariella eErrede

    2014-10-01

    Full Text Available This study was conducted on human developing brain by laser confocal and transmission electron microscopy to make a detailed analysis of important features of blood-brain barrier microvessels and possible control mechanisms of vessel growth and differentiation during cerebral cortex vascularization. The blood-brain barrier status of cortex microvessels was examined at a defined stage of cortex development, at the end of neuroblast waves of migration and before cortex lamination, with blood-brain barrier-endothelial cell markers, namely tight junction proteins (occludin and claudin-5 and influx and efflux transporters (Glut-1 and P-glycoprotein, the latter supporting evidence for functional effectiveness of the fetal blood-brain barrier. According to the well-known roles of astroglia cells on microvessel growth and differentiation, the early composition of astroglia/endothelial cell relationships was analysed by detecting the appropriate astroglia, endothelial, and pericyte markers. GFAP, chemokine CXCL12, and connexin 43 (Cx43 were utilized as markers of radial glia cells, CD105 (endoglin as a marker of angiogenically activated endothelial cells, and proteoglycan NG2 as a marker of immature pericytes. Immunolabeling for CXCL12 showed the highest level of the ligand in radial glial fibres in contact with the growing cortex microvessels. These specialized contacts, recognizable on both perforating radial vessels and growing collaterals, appeared as CXCL12-reactive en passant, symmetrical and asymmetrical vessel-specific RG fibre swellings. At the highest confocal resolution, these RG varicosities showed a CXCL12-reactive dot-like content whose microvesicular nature was confirmed by ultrastructural observations. A further analysis of radial glial varicosities reveals colocalization of CXCL12 with connexin Cx43, which is possibly implicated in vessel-specific chemokine signalling.

  19. Human papillomavirus molecular biology and disease association

    Science.gov (United States)

    Egawa, Nagayasu; Griffin, Heather; Kranjec, Christian; Murakami, Isao

    2015-01-01

    Summary Human papillomaviruses (HPVs) have evolved over millions of years to propagate themselves in a range of different animal species including humans. Viruses that have co‐evolved slowly in this way typically cause chronic inapparent infections, with virion production in the absence of apparent disease. This is the case for many Beta and Gamma HPV types. The Alpha papillomavirus types have however evolved immunoevasion strategies that allow them to cause persistent visible papillomas. These viruses activate the cell cycle as the infected epithelial cell differentiates in order to create a replication competent environment that allows viral genome amplification and packaging into infectious particles. This is mediated by the viral E6, E7, and E5 proteins. High‐risk E6 and E7 proteins differ from their low‐risk counterparts however in being able to drive cell cycle entry in the upper epithelial layers and also to stimulate cell proliferation in the basal and parabasal layers. Deregulated expression of these cell cycle regulators underlies neoplasia and the eventual progression to cancer in individuals who cannot resolve high‐risk HPV infection. Most work to date has focused on the study of high‐risk HPV types such as HPV 16 and 18, which has led to an understanding of the molecular pathways subverted by these viruses. Such approaches will lead to the development of better strategies for disease treatment, including targeted antivirals and immunotherapeutics. Priorities are now focused toward understanding HPV neoplasias at sites other than the cervix (e.g. tonsils, other transformation zones) and toward understanding the mechanisms by which low‐risk HPV types can sometimes give rise to papillomatosis and under certain situations even cancers. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25752814

  20. A Groundwork for Allostatic Neuro-Education

    OpenAIRE

    Lee eGerdes; Tegeler, Charles H; Sung eLee

    2015-01-01

    We propose to enliven educational practice by marrying a conception of education as guided human development, to an advanced scientific understanding of the brain known as allostasis (stability through change). The result is a groundwork for allostatic neuro-education (GANE). Education as development encompasses practices including the organic (homeschooling and related traditions), cognitive acquisition (emphasis on standards and testing), and the constructivist (aimed to support adaptive cr...

  1. A groundwork for allostatic neuro-education

    OpenAIRE

    Gerdes, Lee; Tegeler, Charles H; Lee, Sung W

    2015-01-01

    We propose to enliven educational practice by marrying a conception of education as guided human development, to an advanced scientific understanding of the brain known as allostasis (stability through change). The result is a groundwork for allostatic neuro-education (GANE). Education as development encompasses practices including the organic (homeschooling and related traditions), cognitive acquisition (emphasis on standards and testing), and the constructivist (aimed to support adaptive cr...

  2. Urgences en neuro-ophtalmologie

    DEFF Research Database (Denmark)

    Caignard, A.; Leruez, S.; Milea, D.

    2017-01-01

    Neuro-ophthalmic emergencies can cause life-threatening or sight-threatening complications. Various conditions may have acute neuro-ophthalmic manifestations, including inflammatory or ischemic processes, as well as tumoral, aneurysmal compression or metabolic and systemic diseases. Diplopia rela...

  3. Neuro-fuzzy controller for active ankle foot orthosis

    Directory of Open Access Journals (Sweden)

    Rishabh Kochhar

    2016-09-01

    Full Text Available The ankle foot orthosis (AFO is as an assistive device used in foot disability for gait improvement. The objective of this paper was to design a neuro fuzzy controller for an AFO. Adaptive neuro fuzzy inference system (ANFIS was selected after a detailed study of existing neuro-fuzzy architectures. Data of gait pattern was collected with the help of analog gyro sensors. This data was fed to the ANFIS and a fuzzy rule base was created to complete the neuro-fuzzy system which was used to control the gait pattern. Angular velocity and angle of feet served as inputs to the controller and the output was actuation. The results obtained showed sigmoidal membership functions for the various inputs and outputs due to their close resemblance with the normal human gait. Output of the ANFIS showcased the initial data which was fed to the system; the modified data; changed membership functions and error after training.

  4. Molecular Sex Differences in Human Serum

    NARCIS (Netherlands)

    J.M. Ramsey (Jordan); E. Schwarz (Emanuel); P.C. Guest (Paul); N.J.M. van Beveren (Nico); F.M. Leweke (Marcus); M. Rothermundt (Matthias); B. Bogerts (Bernhard); J. Steiner (Johann); L. Ruta (Liliana); S. Baron-Cohen (Simon); S. Bahn (Sabine)

    2012-01-01

    textabstractBackground: Sex is an important factor in the prevalence, incidence, progression, and response to treatment of many medical conditions, including autoimmune and cardiovascular diseases and psychiatric conditions. Identification of molecular differences between typical males and females

  5. Human exposure to a 60 Hz, 1800 micro tesla magnetic field: a neuro behavioral study; Exposition humaine a un champ magnetique de 1 800 microtesla a 60 Hz: une etude neurocomportementale

    Energy Technology Data Exchange (ETDEWEB)

    Legros, A.; Corbacio, M.; Prato, F.S.; Thomas, A.W. [Lawson Health Research Institute and University of Western Ontario, St Joseph Health' s Care (Canada); Beuter, A. [Laboratoire IMS Institut de Polytechnique de Bordeaux, Universite de Bordeaux, 33 (France); Goulet, D. [Hydro-Quebec TransEnergie, Montreal (Canada); Lambrozo, J.; Souques, M. [Electricite de France, Service des Etudes Medicales, 75 - Paris (France); Plante, M. [Hydro-Quebec, Direction Sante et securite, Montreal (Canada)

    2010-05-15

    The effects of time-varying magnetic fields (MF) on humans have been actively investigated for the past three decades. One important unanswered question that scientists continue to investigate is the potential for MF exposure to have acute effects on human biology. Different strategies have been used to tackle this question using various physiological, neuro-physiological and behavioral indicators. For example, researchers investigating electro-encephalography (EEG) have reported that Extremely Low Frequency (ELF, < 300 Hz) MF can increase the resting occipital alpha rhythm (8-12 Hz) [1, 2]. Interestingly, other studies have demonstrated that human motor behavior can be modulated by ELF MF exposure, reporting that such an exposure can reduce anteroposterior standing balance oscillations [3, 4] or decrease physiological tremor intensity [5]. However, the main limitation in this domain is the difficulty of reproducing the results. A possible reason for this is the large variety of experimental approaches employed. Therefore, the aim of this project is to investigate the effects of a 60 Hz, 1800 muT MF exposure on physiological (i.e. heart rate and peripheral blood perfusion), neuro-physiological (brain electrical activity), and behavioral (postural oscillations, voluntary motor functions, and physiological tremor) aspects in humans using a single experimental procedure.Though the results from this study suggest a subtle reduction of human standing balance as well as a subtle increase of physiological tremor amplitude with MF exposure, no effect appeared on other investigated parameters, suggesting that one hour of 60 Hz, 1800 muT MF exposure may modulate human involuntary motor control without being detected in the electrical activity of the brain. (authors)

  6. Molecular Genetic Study of Human Esophageal Carcinoma

    Science.gov (United States)

    1991-07-16

    virus have been shown to be the causative agent for human cancer, as human papilloma - virus ( HPV ) was associated with...F.J., Syrjanen, S., Shen, Q., J.I, H., & Kyrjanen, K. Human papilloma virus ( HPV ) DNA in esophageal precursor lesions and squamous cell carcinomas...genital tumors. Gene products, such as SV40 tumor antigen, Ela and Elb in adenovirus, E6 and E7 protein of human papilloma virus type 16 and type

  7. Neuro-ophthalmology update.

    Science.gov (United States)

    Weber, Konrad P; Straumann, Dominik

    2014-07-01

    This review summarizes the most relevant articles from the field of neuro-ophthalmology published in the Journal of Neurology from January 2012 to July 2013. With the advent of video-oculography, several articles describe new applications for eye movement recordings as a diagnostic tool for a wide range of disorders. In myasthenia gravis, anti-Kv1.4 and anti-Lrp4 have been characterized as promising novel autoantibodies for the diagnosis of hitherto 'seronegative' myasthenia gravis. Several articles address new diagnostic and therapeutic approaches to neuromyelitis optica, which further sharpen its profile as a distinct entity. Additionally, 4-aminopyridine has become a standard therapeutic for patients with cerebellar downbeat nystagmus. Finally, revised diagnostic criteria have been proposed for chronic relapsing inflammatory optic neuropathy based on a careful literature review over the last decade.

  8. MOLECULAR ANALYSIS OF HUMAN SPERMATOZOA: POTENTIAL FOR INFERTILITY RESEARCH

    Science.gov (United States)

    Gordon Research Conference: Mammalian Gametogenesis and Embryogenesis New London, CT, July 1-6, 2000Molecular Analysis of Human Spermatozoa: Potential for Infertility ResearchDavid Miller 1, David Dix2, Robert Reid 3, Stephen A Krawetz 3 1Reproductive ...

  9. Neuro-ophthalmology as a career

    Science.gov (United States)

    Spitze, Arielle; Al-Zubidi, Nagham; Lam, Peter; Yalamanchili, Sushma; Lee, Andrew G

    2014-01-01

    This essay was written to discuss the reasoning behind the personal decisions made by 2 current neuro-ophthalmology fellows to pursue neuro-ophthalmology as a career. It is meant to enlighten the reader about what role neuro-ophthalmologists play in clinical practice, what makes neuro-ophthalmology unique to all other sub-specialties, and how this contributes to making neuro-ophthalmology not only one of the most medically interesting, yet rewarding sub-specialties in ophthalmology. PMID:25449937

  10. Neuro-ophthalmology as a career.

    Science.gov (United States)

    Spitze, Arielle; Al-Zubidi, Nagham; Lam, Peter; Yalamanchili, Sushma; Lee, Andrew G

    2014-10-01

    This essay was written to discuss the reasoning behind the personal decisions made by 2 current neuro-ophthalmology fellows to pursue neuro-ophthalmology as a career. It is meant to enlighten the reader about what role neuro-ophthalmologists play in clinical practice, what makes neuro-ophthalmology unique to all other sub-specialties, and how this contributes to making neuro-ophthalmology not only one of the most medically interesting, yet rewarding sub-specialties in ophthalmology.

  11. Molecular Epidemiology of Human Immunodeficiency Virus

    OpenAIRE

    Chin, Bum Sik

    2017-01-01

    During the evolution of human immunodeficiency virus (HIV), transmissions between humans and primates resulted in multiple HIV lineages in humans. This evolution has been rapid, giving rise to a complex classification and allowing for worldwide spread and intermixing of subtypes, which has consequently led to dozens of circulating recombinant forms. In the Republic of Korea, 12,522 cases of HIV infection have been reported between 1985, when AIDS was first identified, and 2015. This review fo...

  12. Molecular Gender Determination of Ancient Human from Malay Peninsular

    OpenAIRE

    Z. A.S. Hisham; S. Sahidan; M. A.W. Rohaya; M. Y.S. Afeefah; Z. A.I. Zarina; J. A.N.N. Hidayah; R. M.A. Nadiah; Z. A. Zaidah

    2009-01-01

    Problem statement: DNA samples from fourteen modern human bloods (seven males and seven females) and two ancient skeletal samples excavated from Kalumpang Island and Dungun, Peninsular Malaysia were subjected for molecular genders determination using specific primers of human AMELX and AMELY. Approach: A standard multiple PCR mixture with forward primer and either a human X-specific reverse primer for AMELX or a human Y-specific reverse primer for AMELY amplifications were used to assess the ...

  13. NIH NeuroBioBank

    Data.gov (United States)

    Federal Laboratory Consortium — The NIH NeuroBioBank (NBB), supported by the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and the Eunice Kennedy...

  14. The neuro-ophthalmological examination.

    Science.gov (United States)

    Rucker, Janet C; Kennard, Christopher; Leigh, R John

    2011-01-01

    The neuro-ophthalmological examination constitutes one of the most refined and exact components of the clinical examination, often allowing precise diagnosis and formulation of a treatment plan even within the compass of the first visit. This chapter briefly highlights important features in the neuro-ophthalmological history and then presents detailed information on the important components of a comprehensive neuro-ophthalmological examination. Covered examination topics include visual acuity, visual field testing, color vision, external eye exam, pupils, ophthalmoscopy, and eye movements. The final section discusses ancillary tests that supplement the bedside neuro-ophthalmological examination, including formal visual field analysis, electroretinography, fluorescein angiography, ocular coherence tomography, visual-evoked potentials, neuroimaging, and quantitative eye movement recordings. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. [Neuro-Ophthalmological History Taking].

    Science.gov (United States)

    Wilhelm, Helmut

    2017-11-01

    Neuro-ophthalmological history may be very complex and difficult. This article provides 14 hints about how to construct history taking efficiently and how to avoid collecting unnecessary information. Georg Thieme Verlag KG Stuttgart · New York.

  16. Molecular regulation of human hematopoietic stem cells

    NARCIS (Netherlands)

    van Galen, P.L.J.

    2014-01-01

    Peter van Galen focuses on understanding the determinants that maintain the stem cell state. Using human hematopoietic stem cells (HSCs) as a model, processes that govern self-renewal and tissue regeneration were investigated. Specifically, a role for microRNAs in balancing the human HSC

  17. Cellular and Molecular Anatomy of the Human Neuromuscular Junction

    Directory of Open Access Journals (Sweden)

    Ross A. Jones

    2017-11-01

    Full Text Available The neuromuscular junction (NMJ plays a fundamental role in transferring information from lower motor neuron to skeletal muscle to generate movement. It is also an experimentally accessible model synapse routinely studied in animal models to explore fundamental aspects of synaptic form and function. Here, we combined morphological techniques, super-resolution imaging, and proteomic profiling to reveal the detailed cellular and molecular architecture of the human NMJ. Human NMJs were significantly smaller, less complex, and more fragmented than mouse NMJs. In contrast to mice, human NMJs were also remarkably stable across the entire adult lifespan, showing no signs of age-related degeneration or remodeling. Super-resolution imaging and proteomic profiling revealed distinctive distribution of active zone proteins and differential expression of core synaptic proteins and molecular pathways at the human NMJ. Taken together, these findings reveal human-specific cellular and molecular features of the NMJ that distinguish them from comparable synapses in other mammalian species.

  18. Knowledge environments representing molecular entities for the virtual physiological human.

    Science.gov (United States)

    Hofmann-Apitius, Martin; Fluck, Juliane; Furlong, Laura; Fornes, Oriol; Kolárik, Corinna; Hanser, Susanne; Boeker, Martin; Schulz, Stefan; Sanz, Ferran; Klinger, Roman; Mevissen, Theo; Gattermayer, Tobias; Oliva, Baldo; Friedrich, Christoph M

    2008-09-13

    In essence, the virtual physiological human (VPH) is a multiscale representation of human physiology spanning from the molecular level via cellular processes and multicellular organization of tissues to complex organ function. The different scales of the VPH deal with different entities, relationships and processes, and in consequence the models used to describe and simulate biological functions vary significantly. Here, we describe methods and strategies to generate knowledge environments representing molecular entities that can be used for modelling the molecular scale of the VPH. Our strategy to generate knowledge environments representing molecular entities is based on the combination of information extraction from scientific text and the integration of information from biomolecular databases. We introduce @neuLink, a first prototype of an automatically generated, disease-specific knowledge environment combining biomolecular, chemical, genetic and medical information. Finally, we provide a perspective for the future implementation and use of knowledge environments representing molecular entities for the VPH.

  19. Molecular Sex Differences in Human Serum

    OpenAIRE

    Ramsey, Jordan M.; Emanuel Schwarz; Paul C. Guest; van Beveren, Nico J. M.; Markus Leweke, F.; Matthias Rothermundt; Bernhard Bogerts; Johann Steiner; Liliana Ruta; Simon Baron-Cohen; Sabine Bahn

    2012-01-01

    textabstractBackground: Sex is an important factor in the prevalence, incidence, progression, and response to treatment of many medical conditions, including autoimmune and cardiovascular diseases and psychiatric conditions. Identification of molecular differences between typical males and females can provide a valuable basis for exploring conditions differentially affected by sex. Methodology/Principal Findings: Using multiplexed immunoassays, we analyzed 174 serum molecules in 9 independent...

  20. Molecular pharmacology of human NMDA receptors

    DEFF Research Database (Denmark)

    Hedegaard, Maiken; Hansen, Kasper Bø; Andersen, Karen Toftegaard

    2012-01-01

    current knowledge of the relationship between NMDA receptor structure and function. We summarize studies on the biophysical properties of human NMDA receptors and compare these properties to those of rat orthologs. Finally, we provide a comprehensive pharmacological characterization that allows side......-by-side comparison of agonists, un-competitive antagonists, GluN2B-selective non-competitive antagonists, and GluN2C/D-selective modulators at recombinant human and rat NMDA receptors. The evaluation of biophysical properties and pharmacological probes acting at different sites on the receptor suggest...... that the binding sites and conformational changes leading to channel gating in response to agonist binding are highly conserved between human and rat NMDA receptors. In summary, the results of this study suggest that no major detectable differences exist in the pharmacological and functional properties of human...

  1. Molecular basis of human cerebral malaria development

    OpenAIRE

    Wah, Saw Thu; Hananantachai, Hathairad; Kerdpin, Usanee; Plabplueng, Chotiros; Prachayasittikul, Virapong; Nuchnoi, Pornlada

    2016-01-01

    Cerebral malaria is still a deleterious health problem in tropical countries. The wide spread of malarial drug resistance and the lack of an effective vaccine are obstacles for disease management and prevention. Parasite and human genetic factors play important roles in malaria susceptibility and disease severity. The malaria parasite exerted a potent selective signature on the human genome, which is apparent in the genetic polymorphism landscape of genes related to pathogenesis. Currently, m...

  2. Neuro fuzzy control of the FES assisted freely swinging leg of paraplegic subjects

    NARCIS (Netherlands)

    van der Spek, J.H.; Velthuis, W.J.R.; Veltink, Petrus H.; de Vries, Theodorus J.A.

    1996-01-01

    The authors designed a neuro fuzzy control strategy for control of cyclical leg movements of paraplegic subjects. The cyclical leg movements were specified by three `swing phase objectives', characteristic of natural human gait. The neuro fuzzy controller is a combination of a fuzzy logic controller

  3. Neuro-robotics from brain machine interfaces to rehabilitation robotics

    CERN Document Server

    Artemiadis

    2014-01-01

    Neuro-robotics is one of the most multidisciplinary fields of the last decades, fusing information and knowledge from neuroscience, engineering and computer science. This book focuses on the results from the strategic alliance between Neuroscience and Robotics that help the scientific community to better understand the brain as well as design robotic devices and algorithms for interfacing humans and robots. The first part of the book introduces the idea of neuro-robotics, by presenting state-of-the-art bio-inspired devices. The second part of the book focuses on human-machine interfaces for pe

  4. Neuro Linguistic Programming

    Directory of Open Access Journals (Sweden)

    Suzana Padežanin

    1996-12-01

    Full Text Available The paper is in fact an introduction to the field known as neuro-linguistic programming or NLP. It describes the origins of thi s method and funda­ mental assumptions about NLP -current perception of reality, establishment of rapport, and  development of our unique potential in order to understand the world. The paper furthermore provides insight into how we use our inner senses for reflection , how language and thought interact, and how we can determine the way other people think. The NLP method simultaneousl y takes into consideration all of the personality signals - bod y a nd speech signals, and visua l pattems. NLP assumes tha t the usual framework of interpretation and criticism needs to be transcended in order for us to be able to see matters ina different light, and thus develop better al ternatives for achieving our original goals. The paper emphasizes the inner processing of information, which is captured by certain NLP diagnostic models, thus providing the starting point for change.

  5. Molecular sex differences in human serum.

    Directory of Open Access Journals (Sweden)

    Jordan M Ramsey

    Full Text Available Sex is an important factor in the prevalence, incidence, progression, and response to treatment of many medical conditions, including autoimmune and cardiovascular diseases and psychiatric conditions. Identification of molecular differences between typical males and females can provide a valuable basis for exploring conditions differentially affected by sex.Using multiplexed immunoassays, we analyzed 174 serum molecules in 9 independent cohorts of typical individuals, comprising 196 males and 196 females. Sex differences in analyte levels were quantified using a meta-analysis approach and put into biological context using k-means to generate clusters of analytes with distinct biological functions. Natural sex differences were established in these analyte groups and these were applied to illustrate sexually dimorphic analyte expression in a cohort of 22 males and 22 females with Asperger syndrome. Reproducible sex differences were found in the levels of 77 analytes in serum of typical controls, and these comprised clusters of molecules enriched with distinct biological functions. Analytes involved in fatty acid oxidation/hormone regulation, immune cell growth and activation, and cell death were found at higher levels in females, and analytes involved in immune cell chemotaxis and other indistinct functions were higher in males. Comparison of these naturally occurring sex differences against a cohort of people with Asperger syndrome indicated that a cluster of analytes that had functions related to fatty acid oxidation/hormone regulation was associated with sex and the occurrence of this condition.Sex-specific molecular differences were detected in serum of typical controls and these were reproducible across independent cohorts. This study extends current knowledge of sex differences in biological functions involved in metabolism and immune function. Deviations from typical sex differences were found in a cluster of molecules in Asperger syndrome

  6. Memristive Neuro-Fuzzy System.

    Science.gov (United States)

    Merrikh-Bayat, Farnood; Shouraki, Saeed Bagheri

    2013-02-01

    In this paper, a novel neuro-fuzzy computing system is proposed where its learning is based on the creation of fuzzy relations by using a new implication method without utilizing any exact mathematical techniques. Then, a simple memristor crossbar-based analog circuit is designed to implement this neuro-fuzzy system which offers very interesting properties. In addition to high connectivity between neurons and being fault tolerant, all synaptic weights in our proposed method are always non-negative, and there is no need to adjust them precisely. Finally, this structure is hierarchically expandable, and it can do fuzzy operations in real time since it is implemented through analog circuits. Simulation results confirm the efficiency and applicability of our neuro-fuzzy computing system. They also indicate that this system can be a good candidate to be used for creating artificial brain.

  7. Molecular Modeling of Prion Transmission to Humans

    Directory of Open Access Journals (Sweden)

    Etienne Levavasseur

    2014-10-01

    Full Text Available Using different prion strains, such as the variant Creutzfeldt-Jakob disease agent and the atypical bovine spongiform encephalopathy agents, and using transgenic mice expressing human or bovine prion protein, we assessed the reliability of protein misfolding cyclic amplification (PMCA to model interspecies and genetic barriers to prion transmission. We compared our PMCA results with in vivo transmission data characterized by attack rates, i.e., the percentage of inoculated mice that developed the disease. Using 19 seed/substrate combinations, we observed that a significant PMCA amplification was only obtained when the mouse line used as substrate is susceptible to the corresponding strain. Our results suggest that PMCA provides a useful tool to study genetic barriers to transmission and to study the zoonotic potential of emerging prion strains.

  8. NeuroSim--the prototype of a neurosurgical training simulator.

    Science.gov (United States)

    Beier, Florian; Diederich, Stephan; Schmieder, Kirsten; Männer, Reinhard

    2011-01-01

    We present NeuroSim, the prototype of a training simulator for open surgical interventions on the human brain. The simulator is based on virtual reality and uses real-time simulation algorithms to interact with models generated from MRT- or CT-datasets. NeuroSim provides a native interface by using a real surgical microscope and original instruments tracked by a combination of inertial measurement units and optical tracking. Conclusively an immersive environment is generated. In a first step the navigation in an open surgery setup as well as the hand-eye coordination through a microscope can be trained. Due to its modular design further training modules and extensions can be integrated. NeuroSim has been developed in cooperation with the neurosurgical clinic of the University of Heidelberg and the VRmagic GmbH in Mannheim.

  9. Matters of Taste: Bridging Molecular Physiology and the Humanities

    Science.gov (United States)

    Rangachari, P. K.; Rangachari, Usha

    2015-01-01

    Taste perception was the focus of an undergraduate course in the health sciences that bridged the sciences and humanities. A problem-based learning approach was used to study the biological issues, whereas the cultural transmutations of these molecular mechanisms were explored using a variety of resources (novels, cookbooks, and films). Multiple…

  10. Molecular characterization of human Dirofilaria isolates from Kerala

    Directory of Open Access Journals (Sweden)

    Najuma Nazar

    2017-01-01

    Interpretation & conclusions: Molecular identification of D. repens isolated from human source assumes significance from the point of zoonotic threat of this mosquito-borne nematode. Phylogenetic analysis revealed a close evolutionary relationship with Asian isolate of D. honkongensis. Timely detection and treatment of infection in dogs, together with mosquito control, should be an integral part of the control strategy of this disease.

  11. Molecular Dynamics and Bioactivity of a Novel Mutated Human ...

    African Journals Online (AJOL)

    Purpose: To design and evaluate a novel human parathyroid hormone (hPTH) analog. Methods: Mutation stability prediction was processed on hPTH, docked the mutant hPTH with its receptor, and then proceeded with molecular dynamics using Discovery Studio 3.5 software package for the complex. The bioactivity of the ...

  12. [Molecular anthropology and the origin of modern human].

    Science.gov (United States)

    Sheng, Gui-Lian; Lai, Xu-Long; Wang, Wei

    2004-09-01

    Since Watson & Crick put forward the double-helix model of DNA structure and hereditary mechanism in 1953, it is generally accepted that this event marks the birth of modern molecular biology. This new field of biology has experienced a flourishing development in the past 50 years. On one hand, the development of molecular biology has been deeply influencing many relative fields; on the other hand, its own proceeding pace has been accelerated by the reaction from the other fields. Anthropology is one of the fields most deeply impacted by the theory and method of molecular biology. Most importantly, molecular anthropology was born as a result of combination of molecular biology, anthropology as well as paleoanthropology. This new branch provides reliable method and vital direction for paleoanthropology. This paper systematically reviews the history, principle and method of molecular anthropology. Two hypotheses on the origin of modern human, which include "out-of-African theory" and "theory of multiregional evolution" are also discussed for the purpose of showing how molecular anthropology is applied in paleoanthropology.

  13. Molecular aging and rejuvenation of human muscle stem cells

    DEFF Research Database (Denmark)

    Carlson, Morgan E; Suetta, Charlotte; Conboy, Michael J

    2009-01-01

    Very little remains known about the regulation of human organ stem cells (in general, and during the aging process), and most previous data were collected in short-lived rodents. We examined whether stem cell aging in rodents could be extrapolated to genetically and environmentally variable humans....... Our findings establish key evolutionarily conserved mechanisms of human stem cell aging. We find that satellite cells are maintained in aged human skeletal muscle, but fail to activate in response to muscle attrition, due to diminished activation of Notch compounded by elevated transforming growth...... factor beta (TGF-beta)/phospho Smad3 (pSmad3). Furthermore, this work reveals that mitogen-activated protein kinase (MAPK)/phosphate extracellular signal-regulated kinase (pERK) signalling declines in human muscle with age, and is important for activating Notch in human muscle stem cells. This molecular...

  14. Neuro-ophthalmology as a career

    Directory of Open Access Journals (Sweden)

    Arielle Spitze

    2014-01-01

    Full Text Available This essay was written to discuss the reasoning behind the personal decisions made by 2 current neuro-ophthalmology fellows to pursue neuro-ophthalmology as a career. It is meant to enlighten the reader about what role neuro-ophthalmologists play in clinical practice, what makes neuro-ophthalmology unique to all other sub-specialties, and how this contributes to making neuro-ophthalmology not only one of the most medically interesting, yet rewarding sub-specialties in ophthalmology.

  15. Molecular and physiological manifestations and measurement of aging in humans.

    Science.gov (United States)

    Khan, Sadiya S; Singer, Benjamin D; Vaughan, Douglas E

    2017-08-01

    Biological aging is associated with a reduction in the reparative and regenerative potential in tissues and organs. This reduction manifests as a decreased physiological reserve in response to stress (termed homeostenosis) and a time-dependent failure of complex molecular mechanisms that cumulatively create disorder. Aging inevitably occurs with time in all organisms and emerges on a molecular, cellular, organ, and organismal level with genetic, epigenetic, and environmental modulators. Individuals with the same chronological age exhibit differential trajectories of age-related decline, and it follows that we should assess biological age distinctly from chronological age. In this review, we outline mechanisms of aging with attention to well-described molecular and cellular hallmarks and discuss physiological changes of aging at the organ-system level. We suggest methods to measure aging with attention to both molecular biology (e.g., telomere length and epigenetic marks) and physiological function (e.g., lung function and echocardiographic measurements). Finally, we propose a framework to integrate these molecular and physiological data into a composite score that measures biological aging in humans. Understanding the molecular and physiological phenomena that drive the complex and multifactorial processes underlying the variable pace of biological aging in humans will inform how researchers assess and investigate health and disease over the life course. This composite biological age score could be of use to researchers seeking to characterize normal, accelerated, and exceptionally successful aging as well as to assess the effect of interventions aimed at modulating human aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  16. Pathway reporter genes define molecular phenotypes of human cells.

    Science.gov (United States)

    Zhang, Jitao David; Küng, Erich; Boess, Franziska; Certa, Ulrich; Ebeling, Martin

    2015-04-24

    The phenotype of a living cell is determined by its pattern of active signaling networks, giving rise to a "molecular phenotype" associated with differential gene expression. Digital amplicon based RNA quantification by sequencing is a useful technology for molecular phenotyping as a novel tool to characterize the state of biological systems. We show here that the activity of signaling networks can be assessed based on a set of established key regulators and expression targets rather than the entire transcriptome. We compiled a panel of 917 human pathway reporter genes, representing 154 human signaling and metabolic networks for integrated knowledge- and data-driven understanding of biological processes. The reporter genes are significantly enriched for regulators and effectors covering a wide range of biological processes, and faithfully capture gene-level and pathway-level changes. We apply the approach to iPSC derived cardiomyocytes and primary human hepatocytes to describe changes in molecular phenotype during development or drug response. The reporter genes deliver an accurate pathway-centric view of the biological system under study, and identify known and novel modulation of signaling networks consistent with literature or experimental data. A panel of 917 pathway reporter genes is sufficient to describe changes in the molecular phenotype defined by 154 signaling cascades in various human cell types. AmpliSeq-RNA based digital transcript imaging enables simultaneous monitoring of the entire pathway reporter gene panel in up to 150 samples. We propose molecular phenotyping as a useful approach to understand diseases and drug action at the network level.

  17. Talking to neuro-baby; Onsei de Ningen to komyunikeshon dekiru robotikusu ato:nyuro beibi

    Energy Technology Data Exchange (ETDEWEB)

    Tosa, N. [Musashino Art Univ., Tokyo (Japan). Faculty of Formative

    1995-04-10

    Neuro-baby is an electronic living being having a face of a human baby and can communicate with the human being with a voice. Irrespective to human, one can talk with neuro-baby by switching on the button whenever you like to talk. If one does not like to talk with the baby you can make the switch off. It is a digital living being that can die anytime and can back to life always. The artistic concept of neuro-baby, interactive function, design method of the nature of neuro-baby and study of the relation of the voice and feelings are described. Again, network neuro-baby, neuro-baby that responses to anybody beyond the language barrier developed by joint collaboration with Fujitsu Laboratories Ltd., is introduced. Birth of such kind of neuro-baby is a media art with a system itself as a artistic work, and in future it may expand to the development of common language which can be understood by the people of the world. 5 refs., 6 figs.

  18. Gene Transfer and Molecular Cloning of the Human NGF Receptor

    Science.gov (United States)

    Chao, Moses V.; Bothwell, Mark A.; Ross, Alonzo H.; Koprowski, Hilary; Lanahan, Anthony A.; Buck, C. Randall; Sehgal, Amita

    1986-04-01

    Nerve growth factor (NGF) and its receptor are important in the development of cells derived from the neural crest. Mouse L cell transformants have been generated that stably express the human NGF receptor gene transfer with total human DNA. Affinity cross-linking, metabolic labeling and immunoprecipitation, and equilibrium binding with 125I-labeled NGF revealed that this NGF receptor had the same size and binding characteristics as the receptor from human melanoma cells and rat PC12 cells. The sequences encoding the NGF receptor were molecularly cloned using the human Alu repetitive sequence as a probe. A cosmid clone that contained the human NGF receptor gene allowed efficient transfection and expression of the receptor.

  19. Molecular interaction of PCB153 to human serum albumin: Insights from spectroscopic and molecular modeling studies

    Energy Technology Data Exchange (ETDEWEB)

    Han, Chao; Fang, Senbiao; Cao, Huiming; Lu, Yan; Ma, Yaqiong [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Wei, Dongfeng [Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700 (China); Xie, Xiaoyun [College of Earth and Environmental Science, Lanzhou University, Lanzhou 730000 (China); Liu, Xiaohua [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Li, Xin [College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471003 (China); Fei, Dongqing [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Zhao, Chunyan, E-mail: zhaochy07@lzu.edu.cn [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China)

    2013-03-15

    Highlights: ► We identify the binding mode of PCB153 to human serum albumin (HSA). ► Spectroscopic and molecular modeling results reveal that PCB153 binds at the site II. ► The interaction is mainly governed by hydrophobic and hydrogen bond forces. ► The work helps to probe transporting, distribution and toxicity effect of PCBs. -- Abstract: Polychlorinated biphenyls (PCBs) possessed much potential hazard to environment because of its chemical stability and biological toxicity. Here, we identified the binding mode of a representative compound, PCB153, to human serum albumin (HSA) using fluorescence and molecular dynamics simulation methods. The fluorescence study showed that the intrinsic fluorescence of HSA was quenched by addition of PCB153 through a static quenching mechanism. The thermodynamic analysis proved the binding behavior was mainly governed by hydrophobic force. Furthermore, as evidenced by site marker displacement experiments using two probe compounds, it revealed that PCB153 acted exactly on subdomain IIIA (site II) of HSA. On the other hand, the molecular dynamics studies as well as free energy calculations made another important contribution to understand the conformational changes of HSA and the stability of HSA-PCB153 system. Molecular docking revealed PCB153 can bind in a large hydrophobic activity of subdomain IIIA by the hydrophobic interaction and hydrogen bond interactions between chlorine atoms and residue ASN391. The present work provided reasonable models helping us further understand the transporting, distribution and toxicity effect of PCBs when it spread into human blood serum.

  20. Visual displays and Neuro-Linguistic Programming

    Energy Technology Data Exchange (ETDEWEB)

    Brown-VanHoozer, S.A. [Argonne National Lab., Idaho Falls, ID (United States); VanHoozer, W.R. [Tranceformations Unlimited, Rigby, ID (United States)

    1994-10-01

    Advancement of computer technology is forthcoming at such a rapid pace that the research concerning the interplay of humans and computer technology is lagging far behind. One area of particular concern is the design of visual displays that are pragmatic, ``user friendly,`` and ``user assisting.`` When engineers design visual displays, they generally do so methodically and logically, but only from within their own individual perspective or ``model of the world.`` They select the human aspects which make sense to them and not necessarily to non-engineers, operators, and others. The model design is what the engineer chooses to relate, based on his or her perspective of reality. These choices limit the model design thereby excluding the users` perspective. A set of techniques which can be used to assist the designers in expanding their choices and include the users` model is Neuro-Linguistic Programming (NLP).

  1. Neuro-ophthalmology and neuro-otology update.

    Science.gov (United States)

    Gold, Daniel R; Zee, David S

    2015-12-01

    This review summarizes topical papers from the fields of neuro-ophthalmology and neuro-otology published from August 2013 to February 2015. The main findings are: (1) diagnostic criteria for pseudotumor cerebri have been updated, and the Idiopathic Intracranial Hypertension Treatment Trial evaluated the efficacy of acetazolamide in patients with mild vision loss, (2) categorization of vestibular disorders through history and ocular motor examination is particularly important in the acute vestibular syndrome, where timely distinction between a central or peripheral localization is essential, (3) the newly described "sagging eye syndrome" provides a mechanical explanation for an isolated esodeviation that increases at distance in the aging population and (4) eye movement recordings better define how cerebellar dysfunction and/or sixth nerve palsy may play a role in other patients with esodeviations that increase at distance.

  2. Molecular cartography of the human skin surface in 3D

    Science.gov (United States)

    Bouslimani, Amina; Porto, Carla; Rath, Christopher M.; Wang, Mingxun; Guo, Yurong; Gonzalez, Antonio; Berg-Lyon, Donna; Ackermann, Gail; Moeller Christensen, Gitte Julie; Nakatsuji, Teruaki; Zhang, Lingjuan; Borkowski, Andrew W.; Meehan, Michael J.; Dorrestein, Kathleen; Gallo, Richard L.; Bandeira, Nuno; Knight, Rob; Alexandrov, Theodore; Dorrestein, Pieter C.

    2015-01-01

    The human skin is an organ with a surface area of 1.5–2 m2 that provides our interface with the environment. The molecular composition of this organ is derived from host cells, microbiota, and external molecules. The chemical makeup of the skin surface is largely undefined. Here we advance the technologies needed to explore the topographical distribution of skin molecules, using 3D mapping of mass spectrometry data and microbial 16S rRNA amplicon sequences. Our 3D maps reveal that the molecular composition of skin has diverse distributions and that the composition is defined not only by skin cells and microbes but also by our daily routines, including the application of hygiene products. The technological development of these maps lays a foundation for studying the spatial relationships of human skin with hygiene, the microbiota, and environment, with potential for developing predictive models of skin phenotypes tailored to individual health. PMID:25825778

  3. Molecular cartography of the human skin surface in 3D.

    Science.gov (United States)

    Bouslimani, Amina; Porto, Carla; Rath, Christopher M; Wang, Mingxun; Guo, Yurong; Gonzalez, Antonio; Berg-Lyon, Donna; Ackermann, Gail; Moeller Christensen, Gitte Julie; Nakatsuji, Teruaki; Zhang, Lingjuan; Borkowski, Andrew W; Meehan, Michael J; Dorrestein, Kathleen; Gallo, Richard L; Bandeira, Nuno; Knight, Rob; Alexandrov, Theodore; Dorrestein, Pieter C

    2015-04-28

    The human skin is an organ with a surface area of 1.5-2 m(2) that provides our interface with the environment. The molecular composition of this organ is derived from host cells, microbiota, and external molecules. The chemical makeup of the skin surface is largely undefined. Here we advance the technologies needed to explore the topographical distribution of skin molecules, using 3D mapping of mass spectrometry data and microbial 16S rRNA amplicon sequences. Our 3D maps reveal that the molecular composition of skin has diverse distributions and that the composition is defined not only by skin cells and microbes but also by our daily routines, including the application of hygiene products. The technological development of these maps lays a foundation for studying the spatial relationships of human skin with hygiene, the microbiota, and environment, with potential for developing predictive models of skin phenotypes tailored to individual health.

  4. Primer on molecular genetics. DOE Human Genome Program

    Energy Technology Data Exchange (ETDEWEB)

    1992-04-01

    This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

  5. Molecular cloning and characterization of a novel human kinase ...

    Indian Academy of Sciences (India)

    Unknown

    Molecular cloning and sequencing of PDIK1L cDNA: Human foetal brain polyA+ RNA was purchased from Clontech. (Cat. No. 6525-1). Double-stranded cDNA was prepared with the SMART PCR cDNA Synthesis kit (Clontech,. Cat. No. K1052-1) according to the manufacturer's re- commendation. The cDNAs were digested ...

  6. Rapid molecular identification of human taeniid cestodes by pyrosequencing approach.

    Directory of Open Access Journals (Sweden)

    Tongjit Thanchomnang

    Full Text Available Taenia saginata, T. solium, and T. asiatica are causative agents of taeniasis in humans. The difficulty of morphological identification of human taeniids can lead to misdiagnosis or confusion. To overcome this problem, several molecular methods have been developed, but use of these tends to be time-consuming. Here, a rapid and high-throughput pyrosequencing approach was developed for the identification of three human taeniids originating from various countries. Primers targeting the mitochondrial cytochrome c oxidase subunit 1 (cox1 gene of the three Taenia species were designed. Variations in a 26-nucleotide target region were used for identification. The reproducibility and accuracy of the pyrosequencing technology was confirmed by Sanger sequencing. This technique will be a valuable tool to distinguish between sympatric human taeniids that occur in Thailand, Asia and Pacific countries. This method could potentially be used for the molecular identification of the taeniid species that might be associated with suspicious cysts and lesions, or cyst residues in humans or livestock at the slaughterhouse.

  7. Rapid Molecular Identification of Human Taeniid Cestodes by Pyrosequencing Approach

    Science.gov (United States)

    Thanchomnang, Tongjit; Tantrawatpan, Chairat; Intapan, Pewpan M.; Sanpool, Oranuch; Janwan, Penchom; Lulitanond, Viraphong; Tourtip, Somjintana; Yamasaki, Hiroshi; Maleewong, Wanchai

    2014-01-01

    Taenia saginata, T. solium, and T. asiatica are causative agents of taeniasis in humans. The difficulty of morphological identification of human taeniids can lead to misdiagnosis or confusion. To overcome this problem, several molecular methods have been developed, but use of these tends to be time-consuming. Here, a rapid and high-throughput pyrosequencing approach was developed for the identification of three human taeniids originating from various countries. Primers targeting the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of the three Taenia species were designed. Variations in a 26-nucleotide target region were used for identification. The reproducibility and accuracy of the pyrosequencing technology was confirmed by Sanger sequencing. This technique will be a valuable tool to distinguish between sympatric human taeniids that occur in Thailand, Asia and Pacific countries. This method could potentially be used for the molecular identification of the taeniid species that might be associated with suspicious cysts and lesions, or cyst residues in humans or livestock at the slaughterhouse. PMID:24945530

  8. A rational approach to elucidate human monoamine oxidase molecular selectivity.

    Science.gov (United States)

    Mangiatordi, Giuseppe Felice; Alberga, Domenico; Pisani, Leonardo; Gadaleta, Domenico; Trisciuzzi, Daniela; Farina, Roberta; Carotti, Andrea; Lattanzi, Gianluca; Catto, Marco; Nicolotti, Orazio

    2017-04-01

    Designing highly selective human monoamine oxidase (hMAO) inhibitors is a challenging goal on the road to a more effective treatment of depression and anxiety (inhibition of hMAO-A isoform) as well as neurodegenerative diseases (inhibition of hMAO-B isoform). To uncover the molecular rationale of hMAOs selectivity, two recently prepared 2H-chromene-2-ones, namely compounds 1 and 2, were herein chosen as molecular probes being highly selective toward hMAO-A and hMAO-B, respectively. We performed molecular dynamics (MD) studies on four different complexes, cross-simulating one at a time the two hMAO-isoforms (dimer embedded in a lipid bilayer) with the two considered probes. Our comparative analysis on the obtained 100ns trajectories discloses a stable H-bond interaction between 1 and Gln215 as crucial for ligand selectivity toward hMAO-A whereas a water-mediated interaction might explain the observed hMAO-B selectivity of compound 2. Such hypotheses are further supported by binding free energy calculations carried out applying the molecular mechanics generalized Born surface area (MM-GBSA) method and allowing us to evaluate the contribution of each residue to the observed isoform selectivity. Taken as whole, this study represents the first attempt to explain at molecular level hMAO isoform selectivity and a valuable yardstick for better addressing the design of new and highly selective MAO inhibitors. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Human interphase chromosomes: a review of available molecular cytogenetic technologies

    Directory of Open Access Journals (Sweden)

    Yurov Yuri B

    2010-01-01

    Full Text Available Abstract Human karyotype is usually studied by classical cytogenetic (banding techniques. To perform it, one has to obtain metaphase chromosomes of mitotic cells. This leads to the impossibility of analyzing all the cell types, to moderate cell scoring, and to the extrapolation of cytogenetic data retrieved from a couple of tens of mitotic cells to the whole organism, suggesting that all the remaining cells possess these genomes. However, this is far from being the case inasmuch as chromosome abnormalities can occur in any cell along ontogeny. Since somatic cells of eukaryotes are more likely to be in interphase, the solution of the problem concerning studying postmitotic cells and larger cell populations is interphase cytogenetics, which has become more or less applicable for specific biomedical tasks due to achievements in molecular cytogenetics (i.e. developments of fluorescence in situ hybridization -- FISH, and multicolor banding -- MCB. Numerous interphase molecular cytogenetic approaches are restricted to studying specific genomic loci (regions being, however, useful for identification of chromosome abnormalities (aneuploidy, polyploidy, deletions, inversions, duplications, translocations. Moreover, these techniques are the unique possibility to establish biological role and patterns of nuclear genome organization at suprachromosomal level in a given cell. Here, it is to note that this issue is incompletely worked out due to technical limitations. Nonetheless, a number of state-of-the-art molecular cytogenetic techniques (i.e multicolor interphase FISH or interpahase chromosome-specific MCB allow visualization of interphase chromosomes in their integrity at molecular resolutions. Thus, regardless numerous difficulties encountered during studying human interphase chromosomes, molecular cytogenetics does provide for high-resolution single-cell analysis of genome organization, structure and behavior at all stages of cell cycle.

  10. The molecular basis of hereditary enamel defects in humans.

    Science.gov (United States)

    Wright, J T; Carrion, I A; Morris, C

    2015-01-01

    The formation of human enamel is highly regulated at the molecular level and involves thousands of genes. Requisites for development of this highly mineralized tissue include cell differentiation; production of a unique extracellular matrix; processing of the extracellular matrix; altering of cell function during different stages of enamel formation; cell movement and attachment; regulation of ion and protein movement; and regulation of hydration, pH, and other conditions of the microenvironment, to name just a few. Not surprising, there is a plethora of hereditary conditions with an enamel phenotype. The objective of this review was to identify the hereditary conditions listed on Online Mendelian Inheritance in Man (OMIM) that have an associated enamel phenotype and whether a causative gene has been identified. The OMIM database was searched with the terms amelogenesis, enamel, dental, and tooth, and all results were screened by 2 individuals to determine if an enamel phenotype was identified. Gene and gene product function was reviewed on OMIM and from publications identified in PubMed. The search strategy revealed 91 conditions listed in OMIM as having an enamel phenotype, and of those, 71 have a known molecular etiology or linked genetic loci. The purported protein function of those conditions with a known genetic basis included enzymes, regulatory proteins, extracellular matrix proteins, transcription factors, and transmembrane proteins. The most common enamel phenotype was a deficient amount of enamel, or enamel hypoplasia, with hypomineralization defects being reported less frequently. Knowing these molecular defects allows an initial cataloging of molecular pathways that lead to hereditary enamel defects in humans. This knowledge provides insight into the diverse molecular pathways involved in enamel formation and can be useful when searching for the genetic etiology of hereditary conditions that involve enamel. © International & American Associations for

  11. The etiology and molecular genetics of human pigmentation disorders

    Science.gov (United States)

    Baxter, Laura L.; Pavan, William J.

    2012-01-01

    Pigmentation, defined as the placement of pigment in skin, hair, and eyes for coloration, is distinctive because the location, amount, and type of pigmentation provides a visual manifestation of genetic heterogeneity in pathways regulating the pigment-producing cells, melanocytes. The scope of this genetic heterogeneity in humans ranges from normal to pathological pigmentation phenotypes. Clinically normal human pigmentation encompasses a variety of skin and hair color as well as with punctate pigmentation such as melanocytic nevi (moles) or ephelides (freckles), while clinically abnormal human pigmentation exhibits markedly reduced or increased pigment levels, known as hypopigmentation and hyperpigmentation, respectively. Elucidation of the molecular genetics underlying pigmentation has revealed genes important for melanocyte development and function. Furthermore, many pigmentation disorders show additional defects in cells other than melanocytes, and identification of the genetic insults in these disorders has revealed pleiotropic genes, where a single gene is required for various functions, often in different cell types. Thus unravelling the genetics of easily visualized pigmentation disorders has identified molecular similarities between melanocytes and less visible cell types/tissues, revealing a common cellular origin and/or common genetic regulatory pathways. Herein we discuss notable human pigmentation disorders and their associated genetic alterations, focusing on the fact that the developmental genetics of pigmentation abnormalities is instructive for understanding normal pathways governing development and function of melanocytes. PMID:23799582

  12. Molecular identification of four phenotypes of human Demodex in China.

    Science.gov (United States)

    Hu, Li; Zhao, Ya-E; Cheng, Juan; Ma, Jun-Xian

    2014-07-01

    Traditional classification of Demodex mites by hosts and phenotypic characteristics is defective because of environmental influences. In this study, we proposed molecular identification of four phenotypes of two human Demodex species based on mitochondrial cox1 fragments for the first time. Mites collected from sufferers' facial skin were classified into four phenotypes: phenotype A-C with finger-like terminus, and phenotype D with cone-like terminus. The results of molecular data showed that cox1 sequences were all 429 bp. Divergences, genetic distances and transition/transversion ratios among the three phenotypes with finger-like terminus were 0.0-3.0%, 0.000-0.031, and 6/3-5/0, respectively, in line with intraspecific differences. However, those measures between the phenotype with cone-like terminus and phenotypes with finger-like terminus were 19.6-20.5%, 0.256-0.271, and 0.58 (31/53)-0.66 (35/53), respectively, reaching interspecific level. Phylogenetic trees also showed that the three phenotypes with finger-like terminus clustered as one clade, and the phenotype with cone-like terminus formed another one. Therefore, we conclude that mitochondrial cox1 sequence is a good marker for identification of two human Demodex species. Molecular data indicate no subspecies differentiation. Terminus is an effective character for species identification. Mites with finger-like terminus are Demodex folliculorum, and those with cone-like terminus are Demodex brevis. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. The Structure of Human Neuromuscular Junctions: Some Unanswered Molecular Questions

    Directory of Open Access Journals (Sweden)

    Clarke R. Slater

    2017-10-01

    Full Text Available The commands that control animal movement are transmitted from motor neurons to their target muscle cells at the neuromuscular junctions (NMJs. The NMJs contain many protein species whose role in transmission depends not only on their inherent properties, but also on how they are distributed within the complex structure of the motor nerve terminal and the postsynaptic muscle membrane. These molecules mediate evoked chemical transmitter release from the nerve and the action of that transmitter on the muscle. Human NMJs are among the smallest known and release the smallest number of transmitter “quanta”. By contrast, they have the most deeply infolded postsynaptic membranes, which help to amplify transmitter action. The same structural features that distinguish human NMJs make them particularly susceptible to pathological processes. While much has been learned about the molecules which mediate transmitter release and action, little is known about the molecular processes that control the growth of the cellular and subcellular components of the NMJ so as to give rise to its mature form. A major challenge for molecular biologists is to understand the molecular basis for the development and maintenance of functionally important aspects of NMJ structure, and thereby to point to new directions for treatment of diseases in which neuromuscular transmission is impaired.

  14. Defining the molecular signatures of human right heart failure.

    Science.gov (United States)

    Williams, Jordan L; Cavus, Omer; Loccoh, Emefah C; Adelman, Sara; Daugherty, John C; Smith, Sakima A; Canan, Benjamin; Janssen, Paul M L; Koenig, Sara; Kline, Crystal F; Mohler, Peter J; Bradley, Elisa A

    2018-03-01

    Right ventricular failure (RVF) varies significantly from the more common left ventricular failure (LVF). This study was undertaken to determine potential molecular pathways that are important in human right ventricular (RV) function and may mediate RVF. We analyzed mRNA of human non-failing LV and RV samples and RVF samples from patients with pulmonary arterial hypertension (PAH), and post-LVAD implantation. We then performed transcript analysis to determine differential expression of genes in the human heart samples. Immunoblot quantification was performed followed by analysis of non-failing and failing phenotypes. Inflammatory pathways were more commonly dysregulated in RV tissue (both non-failing and failing phenotypes). In non-failing human RV tissue we found important differences in expression of FIGF, TRAPPAC, and CTGF suggesting that regulation of normal RV and LV function are not the same. In failing RV tissue, FBN2, CTGF, SMOC2, and TRAPP6AC were differentially expressed, and are potential targets for further study. This work provides some of the first analyses of the molecular heterogeneity between human RV and LV tissue, as well as key differences in human disease (RVF secondary to pulmonary hypertension and LVAD mediated RVF). Our transcriptional data indicated that inflammatory pathways may be more important in RV tissue, and changes in FIGF and CTGF supported this hypothesis. In PAH RV failure samples, upregulation of FBN2 and CTGF further reinforced the potential significance that altered remodeling and inflammation play in normal RV function and failure. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Neuro-Sweet Disease Causing Orbital Inflammation.

    Science.gov (United States)

    Taravati, Parisa

    2015-02-01

    Neuro-Sweet disease is a rare condition causing encephalitis or meningitis in addition to the erythematous skin plaques of Sweet syndrome. Neuro-Sweet disease has been associated with several ocular manifestations, including ocular movement disorders, episcleritis, conjunctivitis, uveitis, and optic disc oedema. The author reports a patient with orbital inflammation, cranial neuropathies, and a skin rash in the setting of myelodysplastic syndrome. Biopsy of her skin lesion confirmed the diagnosis of neuro-Sweet disease. To the author's knowledge, this is the first reported case of neuro-Sweet disease causing orbital inflammation. Her ocular inflammation resolved with the use of systemic corticosteroid treatment.

  16. Neuro magnetic stimulation: Engineering aspects

    Science.gov (United States)

    Al-Mutawaly, Nafia

    . The motor responses of the thenar muscle were then recorded. The study results show that the biphasic stimulating pulse is more effective than the monophasic pulse, as has been concluded by other researchers. However, the effective stimulating point, or virtual cathode of the coil, was found to be not simply 3 to 4 cm from the coil center as had been reported. In fact, the study shows that the site of the virtual cathode is affected by the current amplitude and the degree of inhomogeneity of the tissues surrounding the nerve. Furthermore, reversing the coil current direction results in a different level of stimulation but does not affect the virtual cathode position. In summary, the research presented in this thesis covers theoretical concepts, experimental aspects, and human studies related to neuro magnetic stimulation. The results of the experiment and the study are consistent with the theoretical analysis. The proposed coil design is novel and offers promise for a better coil system for magnetic nerve stimulation. (Abstract shortened by UMI.)

  17. Research progress in neuro-immune interactions in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Jin-ling CAI

    2012-09-01

    Full Text Available The innate immune response may be activated quickly once the organism is invaded by exotic pathogens. An excessive immune response may result in inflammation and tissue damage, whereas an insufficient immune response may result in infection. Nervous system may regulate the intensity of innate immune responses by releasing neurotransmitters, neuropeptides and hormones. Compared with the complicated neuro-immune system in mammals, it is much simpler in Caenorhabditis elegans. Besides, C. elegans is accessible to genetic, molecular biology and behavioral analyses, so it has been used in studies on neuro-immune interactions. It has been revealed recently in the studies with C. elegans that the neuronal pathways regulating innate immune responses primarily include a transforming growth factor-β (TGF-β pathway, an insulin/insulin-like growth factor receptor (IGF pathway and dopaminergic neurotransmission. Since these pathways are evolutionally conservative, so it might be able to provide some new ideas for the research on neuro-immune interactions at molecular levels. The recent progress in this field has been reviewed in present paper.

  18. Identification of molecules derived from human fibroblast feeder cells that support the proliferation of human embryonic stem cells

    DEFF Research Database (Denmark)

    Anisimov, Sergey V.; Christophersen, Nicolaj S.; Correia, Ana S.

    2011-01-01

    , intermediate and late passages using a custom DNA microarray platform (NeuroStem 2.0 Chip). The microarray data was validated using RT-PCR and virtual SAGE analysis. Our comparative gene expression study identified a limited number of molecular targets potentially involved in the ability of human neonatal...

  19. Facial expressions, their communicatory functions and neuro-cognitive substrates.

    OpenAIRE

    Blair, R J R

    2003-01-01

    Human emotional expressions serve a crucial communicatory role allowing the rapid transmission of valence information from one individual to another. This paper will review the literature on the neural mechanisms necessary for this communication: both the mechanisms involved in the production of emotional expressions and those involved in the interpretation of the emotional expressions of others. Finally, reference to the neuro-psychiatric disorders of autism, psychopathy and acquired sociopa...

  20. Molecularly imprinted composite cryogels for hemoglobin depletion from human blood.

    Science.gov (United States)

    Baydemir, Gözde; Andaç, Müge; Perçin, Işιk; Derazshamshir, Ali; Denizli, Adil

    2014-09-01

    A molecularly imprinted composite cryogel (MICC) was prepared for depletion of hemoglobin from human blood prior to use in proteome applications. Poly(hydroxyethyl methacrylate) based MICC was prepared with high gel fraction yields up to 90%, and characterized by Fourier transform infrared spectrophotometer, scanning electron microscopy, swelling studies, flow dynamics and surface area measurements. MICC exhibited a high binding capacity and selectivity for hemoglobin in the presence of immunoglobulin G, albumin and myoglobin. MICC column was successfully applied in fast protein liquid chromatography system for selective depletion of hemoglobin for human blood. The depletion ratio was highly increased by embedding microspheres into the cryogel (93.2%). Finally, MICC can be reused many times with no apparent decrease in hemoglobin adsorption capacity. Copyright © 2014 John Wiley & Sons, Ltd.

  1. A Groundwork for Allostatic Neuro-Education

    Directory of Open Access Journals (Sweden)

    Lee eGerdes

    2015-08-01

    Full Text Available We propose to enliven educational practice by marrying a conception of education as guided human development, to an advanced scientific understanding of the brain known as allostasis (stability through change. The result is a groundwork for allostatic neuro-education (GANE. Education as development encompasses practices including the organic (homeschooling and related traditions, cognitive acquisition (emphasis on standards and testing, and the constructivist (aimed to support adaptive creativity for both learner and society. Allostasis views change to be the norm in biology, defines success in contexts of complex natural environments rather than controlled settings, and identifies the brain as the organ of central command. Allostatic neuro-education contrasts with education focused exclusively on testing, or neuroscience based on homeostasis (stability through constancy. The GANE perspective is to view the learner in terms of their neurodevelopmental trajectories; its objective is to support authentic freedom, mediated by competent, integrated, and expansive executive functionality (concordant with the philosophy of freedom of Rudolf Steiner; and its strategy is to be attuned to rhythms in various forms (including those of autonomic arousal described in polyvagal theory so as to enable experiential excitement for learning. The GANE presents a variety of testable hypotheses, and studies that explore prevention or mitigation of the effects of early life adversity or toxic stress on learning and development may be of particular importance. Case studies are presented illustrating use of allostatic neurotechnology by an adolescent male carrying diagnoses of Asperger’s Syndrome and attention-deficit hyperactivity disorder, and a grade school girl with reading difficulties. The GANE is intended as a re-visioning of education that may serve both learners and society to be better prepared for the accelerating changes of the twenty-first century.

  2. A groundwork for allostatic neuro-education

    Science.gov (United States)

    Gerdes, Lee; Tegeler, Charles H.; Lee, Sung W.

    2015-01-01

    We propose to enliven educational practice by marrying a conception of education as guided human development, to an advanced scientific understanding of the brain known as allostasis (stability through change). The result is a groundwork for allostatic neuro-education (GANE). Education as development encompasses practices including the organic (homeschooling and related traditions), cognitive acquisition (emphasis on standards and testing), and the constructivist (aimed to support adaptive creativity for both learner and society). Allostasis views change to be the norm in biology, defines success in contexts of complex natural environments rather than controlled settings, and identifies the brain as the organ of central command. Allostatic neuro-education contrasts with education focused dominantly on testing, or neuroscience based on homeostasis (stability through constancy). The GANE perspective is to view learners in terms of their neurodevelopmental trajectories; its objective is to support authentic freedom, mediated by competent, integrated, and expansive executive functionality (concordant with the philosophy of freedom of Rudolf Steiner); and its strategy is to be attuned to rhythms in various forms (including those of autonomic arousal described in polyvagal theory) so as to enable experiential excitement for learning. The GANE presents a variety of testable hypotheses, and studies that explore prevention or mitigation of the effects of early life adversity or toxic stress on learning and development may be of particular importance. Case studies are presented illustrating use of allostatic neurotechnology by an adolescent male carrying diagnoses of Asperger’s syndrome and attention-deficit hyperactivity disorder, and a grade school girl with reading difficulties. The GANE is intended as a re-visioning of education that may serve both learners and society to be better prepared for the accelerating changes of the 21st century. PMID:26347688

  3. A groundwork for allostatic neuro-education.

    Science.gov (United States)

    Gerdes, Lee; Tegeler, Charles H; Lee, Sung W

    2015-01-01

    We propose to enliven educational practice by marrying a conception of education as guided human development, to an advanced scientific understanding of the brain known as allostasis (stability through change). The result is a groundwork for allostatic neuro-education (GANE). Education as development encompasses practices including the organic (homeschooling and related traditions), cognitive acquisition (emphasis on standards and testing), and the constructivist (aimed to support adaptive creativity for both learner and society). Allostasis views change to be the norm in biology, defines success in contexts of complex natural environments rather than controlled settings, and identifies the brain as the organ of central command. Allostatic neuro-education contrasts with education focused dominantly on testing, or neuroscience based on homeostasis (stability through constancy). The GANE perspective is to view learners in terms of their neurodevelopmental trajectories; its objective is to support authentic freedom, mediated by competent, integrated, and expansive executive functionality (concordant with the philosophy of freedom of Rudolf Steiner); and its strategy is to be attuned to rhythms in various forms (including those of autonomic arousal described in polyvagal theory) so as to enable experiential excitement for learning. The GANE presents a variety of testable hypotheses, and studies that explore prevention or mitigation of the effects of early life adversity or toxic stress on learning and development may be of particular importance. Case studies are presented illustrating use of allostatic neurotechnology by an adolescent male carrying diagnoses of Asperger's syndrome and attention-deficit hyperactivity disorder, and a grade school girl with reading difficulties. The GANE is intended as a re-visioning of education that may serve both learners and society to be better prepared for the accelerating changes of the 21st century.

  4. Neuro-ophthalmology in the Horse.

    Science.gov (United States)

    Myrna, Kathern E

    2017-12-01

    This article provides a brief, clinically relevant review of neurologic disorders of the eye. A description of the neuro-ophthalmic examination is provided. Stepwise descriptions of the most common neuro-ophthalmic abnormalities are provided along with common rule outs. Published by Elsevier Inc.

  5. Molecular networks of human muscle adaptation to exercise and age.

    Directory of Open Access Journals (Sweden)

    Bethan E Phillips

    2013-03-01

    Full Text Available Physical activity and molecular ageing presumably interact to precipitate musculoskeletal decline in humans with age. Herein, we have delineated molecular networks for these two major components of sarcopenic risk using multiple independent clinical cohorts. We generated genome-wide transcript profiles from individuals (n = 44 who then undertook 20 weeks of supervised resistance-exercise training (RET. Expectedly, our subjects exhibited a marked range of hypertrophic responses (3% to +28%, and when applying Ingenuity Pathway Analysis (IPA up-stream analysis to ~580 genes that co-varied with gain in lean mass, we identified rapamycin (mTOR signaling associating with growth (P = 1.4 × 10(-30. Paradoxically, those displaying most hypertrophy exhibited an inhibited mTOR activation signature, including the striking down-regulation of 70 rRNAs. Differential analysis found networks mimicking developmental processes (activated all-trans-retinoic acid (ATRA, Z-score = 4.5; P = 6 × 10(-13 and inhibited aryl-hydrocarbon receptor signaling (AhR, Z-score = -2.3; P = 3 × 10(-7 with RET. Intriguingly, as ATRA and AhR gene-sets were also a feature of endurance exercise training (EET, they appear to represent "generic" physical activity responsive gene-networks. For age, we found that differential gene-expression methods do not produce consistent molecular differences between young versus old individuals. Instead, utilizing two independent cohorts (n = 45 and n = 52, with a continuum of subject ages (18-78 y, the first reproducible set of age-related transcripts in human muscle was identified. This analysis identified ~500 genes highly enriched in post-transcriptional processes (P = 1 × 10(-6 and with negligible links to the aforementioned generic exercise regulated gene-sets and some overlap with ribosomal genes. The RNA signatures from multiple compounds all targeting serotonin, DNA topoisomerase antagonism, and RXR activation were significantly related to

  6. Religious Experience from a Neuro-Psychological View

    Directory of Open Access Journals (Sweden)

    Hadi Vakili

    2011-08-01

    Full Text Available The search for the basis of religious experience among neurological processes in the brain has resulted in a widespread debate within, as well as outside the academic world. The aim of this paper is to analyze to what extent a neuro-psychological theory could explain the phenomenon of  religious experience. To clarify what the neuro-psychological studies of  the present paper mean by the concept of  religious experience, the concept has been divided into three different types: The Erlebnis or RErl type, the Erfahrung or RErf type and the ideological type of religious experience or RIT type. Furthermore, the present paper is focused on the work of neuro-psychologist M. A. Persinger [1997, 1993, 1992, 1991, 1987, 1985, and 1984]. In his studies, Persinger indicates that mystical experience (RErl has its seat in the right hemisphere of the human brain, whereas (religious ideology (RIT is related to the left hemisphere. Consequently, the hemisphere in which the (religious experience is taking place seems to label the type of experience. Persinger, interested in the powerful effects of religious experience (of the RErf type on human beings, asserts that if we could understand the neuro-cognitive processes involved in experiencing religiously, such processes might be copied for clinical use in order to improve psychiatric therapy for curing depression. Thus, Persinger studied and compared people practicing religious meditation with people who did not, and also studied the results of PET scanning on the experiences of schizophrenic and epileptic patients. PET scanning measures the metabolic activity in the hemispheres, ranging it on a scale from under normal to over normal activity. This paper will account for the relevance of comparing these two apparently different studies and for the problem arising the experience of pain because, neurologically, pain, like religious experience,is said to be caused by processes in the human brain.

  7. Molecular and Epigenetic Mechanisms of MLL in Human Leukemogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ballabio, Erica; Milne, Thomas A., E-mail: thomas.milne@imm.ox.ac.uk [MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital Headington, Oxford OX3 9DS (United Kingdom)

    2012-09-10

    Epigenetics is often defined as the study of heritable changes in gene expression or chromosome stability that don’t alter the underlying DNA sequence. Epigenetic changes are established through multiple mechanisms that include DNA methylation, non-coding RNAs and the covalent modification of specific residues on histone proteins. It is becoming clear not only that aberrant epigenetic changes are common in many human diseases such as leukemia, but that these changes by their very nature are malleable, and thus are amenable to treatment. Epigenetic based therapies have so far focused on the use of histone deacetylase (HDAC) inhibitors and DNA methyltransferase inhibitors, which tend to have more general and widespread effects on gene regulation in the cell. However, if a unique molecular pathway can be identified, diseases caused by epigenetic mechanisms are excellent candidates for the development of more targeted therapies that focus on specific gene targets, individual binding domains, or specific enzymatic activities. Designing effective targeted therapies depends on a clear understanding of the role of epigenetic mutations during disease progression. The Mixed Lineage Leukemia (MLL) protein is an example of a developmentally important protein that controls the epigenetic activation of gene targets in part by methylating histone 3 on lysine 4. MLL is required for normal development, but is also mutated in a subset of aggressive human leukemias and thus provides a useful model for studying the link between epigenetic cell memory and human disease. The most common MLL mutations are chromosome translocations that fuse the MLL gene in frame with partner genes creating novel fusion proteins. In this review, we summarize recent work that argues MLL fusion proteins could function through a single molecular pathway, but we also highlight important data that suggests instead that multiple independent mechanisms underlie MLL mediated leukemogenesis.

  8. Molecular and Epigenetic Mechanisms of MLL in Human Leukemogenesis

    Directory of Open Access Journals (Sweden)

    Thomas A. Milne

    2012-09-01

    Full Text Available Epigenetics is often defined as the study of heritable changes in gene expression or chromosome stability that don’t alter the underlying DNA sequence. Epigenetic changes are established through multiple mechanisms that include DNA methylation, non-coding RNAs and the covalent modification of specific residues on histone proteins. It is becoming clear not only that aberrant epigenetic changes are common in many human diseases such as leukemia, but that these changes by their very nature are malleable, and thus are amenable to treatment. Epigenetic based therapies have so far focused on the use of histone deacetylase (HDAC inhibitors and DNA methyltransferase inhibitors, which tend to have more general and widespread effects on gene regulation in the cell. However, if a unique molecular pathway can be identified, diseases caused by epigenetic mechanisms are excellent candidates for the development of more targeted therapies that focus on specific gene targets, individual binding domains, or specific enzymatic activities. Designing effective targeted therapies depends on a clear understanding of the role of epigenetic mutations during disease progression. The Mixed Lineage Leukemia (MLL protein is an example of a developmentally important protein that controls the epigenetic activation of gene targets in part by methylating histone 3 on lysine 4. MLL is required for normal development, but is also mutated in a subset of aggressive human leukemias and thus provides a useful model for studying the link between epigenetic cell memory and human disease. The most common MLL mutations are chromosome translocations that fuse the MLL gene in frame with partner genes creating novel fusion proteins. In this review, we summarize recent work that argues MLL fusion proteins could function through a single molecular pathway, but we also highlight important data that suggests instead that multiple independent mechanisms underlie MLL mediated leukemogenesis.

  9. From 'Hard' Neuro-Tools to 'Soft' Neuro-Toys? Refocussing the Neuro-Enhancement Debate.

    Science.gov (United States)

    Brenninkmeijer, Jonna; Zwart, Hub

    2017-01-01

    Since the 1990's, the debate concerning the ethical, legal and societal aspects of 'neuro-enhancement' has evolved into a massive discourse, both in the public realm and in the academic arena. This ethical debate, however, tends to repeat the same sets of arguments over and over again. Normative disagreements between transhumanists and bioconservatives on invasive or radical brain stimulators, and uncertainties regarding the use and effectivity of nootropic pharmaceuticals dominate the field. Building on the results of an extensive European project on responsible research and innovation in neuro-enhancement (NERRI), we observe and encourage that the debate is now entering a new and, as we will argue, more realistic and societally relevant stage. This new stage concerns those technologies that enter the market as ostensibly harmless contrivances that consumers may use for self-care or entertainment. We use the examples and arguments of participants in NERRI debates to describe three case studies of such purportedly innocent 'toys'. Based upon this empirical material, we argue that these 'soft' enhancement gadgets are situated somewhere in the boundary zone between the internal and the external, between the intimate and the intrusive, between the familiar and the unfamiliar, between the friendly and the scary and, in Foucauldian terms, between technologies of the self and technologies of control. Therefore, we describe their physiognomy with the help of a term borrowed from Jacques Lacan, namely as "extimate" technologies.

  10. Molecular Epidemiology of Human Oral Chagas Disease Outbreaks in Colombia

    Science.gov (United States)

    Ramírez, Juan David; Montilla, Marleny; Cucunubá, Zulma M.; Floréz, Astrid Carolina; Zambrano, Pilar; Guhl, Felipe

    2013-01-01

    Background Trypanosoma cruzi, the causative agent of Chagas disease, displays significant genetic variability revealed by six Discrete Typing Units (TcI-TcVI). In this pathology, oral transmission represents an emerging epidemiological scenario where different outbreaks associated to food/beverages consumption have been reported in Argentina, Bolivia, Brazil, Ecuador and Venezuela. In Colombia, six human oral outbreaks have been reported corroborating the importance of this transmission route. Molecular epidemiology of oral outbreaks is barely known observing the incrimination of TcI, TcII, TcIV and TcV genotypes. Methodology and Principal Findings High-throughput molecular characterization was conducted performing MLMT (Multilocus Microsatellite Typing) and mtMLST (mitochondrial Multilocus Sequence Typing) strategies on 50 clones from ten isolates. Results allowed observing the occurrence of TcI, TcIV and mixed infection of distinct TcI genotypes. Thus, a majority of specific mitochondrial haplotypes and allelic multilocus genotypes associated to the sylvatic cycle of transmission were detected in the dataset with the foreseen presence of mitochondrial haplotypes and allelic multilocus genotypes associated to the domestic cycle of transmission. Conclusions These findings suggest the incrimination of sylvatic genotypes in the oral outbreaks occurred in Colombia. We observed patterns of super-infection and/or co-infection with a tailored association with the severe forms of myocarditis in the acute phase of the disease. The transmission dynamics of this infection route based on molecular epidemiology evidence was unraveled and the clinical and biological implications are discussed. PMID:23437405

  11. Low molecular weight silicones particularly facilitate human serum albumin denaturation.

    Science.gov (United States)

    Nayef, Lamees M; Khan, Madiha F; Brook, Michael A

    2015-04-01

    There is a market trend towards the administration of therapeutic proteins using sterilized, pre-filled glass syringes lubricated with silicone oil. It has been widely reported that initially clear solutions of proteins can become turbid during transport and storage, with unclear outcomes with respect to bioefficacy. While the basic processes of interactions of proteins with hydrophobic entities, leading to denaturation and aggregation, are increasingly well understood, the apparently random occurrence of such processes in syringes is not. To better understand the parameters that may be responsible for this change, we report the systematic examination of a series of factors that can affect the behavior of the protein human serum albumin (HSA) when in contact with silicone oil in water. Fluorescence spectroscopy showed that greater mixing times and greater concentrations of silicones (polydimethylsiloxane (PDMS)), especially lower molecular weight hydrophobic silicones like octamethyltetracyclosiloxane (D4), were associated with increased protein denaturation. The turbidity of HSA solutions, due to the formation both of silicone oil-in-water (O/W) emulsions and protein aggregates, was also facilitated by the presence of D4. A series of mixtures of silicone oils, all of which exhibited a viscosity of 1000 cSt but which were comprised of different silicone constituents, clearly showed a correlation between the presence of lower molecular silicones and enhanced solution turbidity. While the addition of a non-ionic silicone-polyether surfactant led to greater turbidity by increasing the number of stabilized oil droplets, it was not accompanied by protein denaturation. These results are consistent with HSA denaturation and subsequent aggregation as a consequence of contact particularly with low molecular weight, hydrophobic silicones that are more mobile, leading to more efficient protein/silicone contact. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Comparative Molecular Dynamics Studies of Human DNA Polymerase η

    Science.gov (United States)

    2015-01-01

    High-energy ultraviolet radiation damages DNA through the formation of cyclobutane pyrimidine dimers, which stall replication. When the lesion is a thymine–thymine dimer (TTD), human DNA polymerase η (Pol η) assists in resuming the replication process by inserting nucleotides opposite the damaged site. We performed extensive molecular dynamics (MD) simulations to investigate the structural and dynamical effects of four different Pol η complexes with or without a TTD and with either dATP or dGTP as the incoming base. No major differences in the overall structures and equilibrium dynamics were detected among the four systems, suggesting that the specificity of this enzyme is due predominantly to differences in local interactions in the binding regions. Analysis of the hydrogen-bonding interactions between the enzyme and the DNA and dNTP provided molecular-level insights. Specifically, the TTD was observed to engage in more hydrogen-bonding interactions with the enzyme than its undamaged counterpart of two normal thymines. The resulting greater rigidity and specific orientation of the TTD are consistent with the experimental observation of higher processivity and overall efficiency at TTD sites than at analogous sites with two normal thymines. The similarities between the systems containing dATP and dGTP are consistent with the experimental observation of relatively low fidelity with respect to the incoming base. Moreover, Q38 and R61, two strictly conserved amino acids across the Pol η family, were found to exhibit persistent hydrogen-bonding interactions with the TTD and cation-π interactions with the free base, respectively. Thus, these simulations provide molecular level insights into the basis for the selectivity and efficiency of this enzyme, as well as the roles of the two most strictly conserved residues. PMID:26562587

  13. Molecular epidemiology of human oral Chagas disease outbreaks in Colombia.

    Directory of Open Access Journals (Sweden)

    Juan David Ramírez

    Full Text Available BACKGROUND: Trypanosoma cruzi, the causative agent of Chagas disease, displays significant genetic variability revealed by six Discrete Typing Units (TcI-TcVI. In this pathology, oral transmission represents an emerging epidemiological scenario where different outbreaks associated to food/beverages consumption have been reported in Argentina, Bolivia, Brazil, Ecuador and Venezuela. In Colombia, six human oral outbreaks have been reported corroborating the importance of this transmission route. Molecular epidemiology of oral outbreaks is barely known observing the incrimination of TcI, TcII, TcIV and TcV genotypes. METHODOLOGY AND PRINCIPAL FINDINGS: High-throughput molecular characterization was conducted performing MLMT (Multilocus Microsatellite Typing and mtMLST (mitochondrial Multilocus Sequence Typing strategies on 50 clones from ten isolates. Results allowed observing the occurrence of TcI, TcIV and mixed infection of distinct TcI genotypes. Thus, a majority of specific mitochondrial haplotypes and allelic multilocus genotypes associated to the sylvatic cycle of transmission were detected in the dataset with the foreseen presence of mitochondrial haplotypes and allelic multilocus genotypes associated to the domestic cycle of transmission. CONCLUSIONS: These findings suggest the incrimination of sylvatic genotypes in the oral outbreaks occurred in Colombia. We observed patterns of super-infection and/or co-infection with a tailored association with the severe forms of myocarditis in the acute phase of the disease. The transmission dynamics of this infection route based on molecular epidemiology evidence was unraveled and the clinical and biological implications are discussed.

  14. [Molecular basis of oncogenesis induced by human papilloma viruses].

    Science.gov (United States)

    Korita, P V; Trotsenko, O E; Annenkov, A Iu; Filimonov, V V

    2012-01-01

    Human papilloma viruses (HPV) of high carcinogenesis risk play important role in development of cancer of oropharyngeal and anogenital areas. Possible malignant transformation of cells, infected by HPV, is due to the expression of three proteins, E6, E7 and E5. These proteins mostly influence on mechanisms that regulate cellular cycle, proliferation and apoptosis inducing and maintaining oncogenesis. This review briefly presents data on malignant tumors induced by HPV as well as biology of these viruses and their vital cycle. Special accent is made on description of current trends in molecular basis of oncogenesis, induced by HPV, which understanding is necessary for elaboration of new methods of treatment for HPV-infection such as therapeutic vaccines.

  15. Matters of taste: bridging molecular physiology and the humanities.

    Science.gov (United States)

    Rangachari, P K; Rangachari, Usha

    2015-12-01

    Taste perception was the focus of an undergraduate course in the health sciences that bridged the sciences and humanities. A problem-based learning approach was used to study the biological issues, whereas the cultural transmutations of these molecular mechanisms were explored using a variety of resources (novels, cookbooks, and films). Multiple evaluation procedures were used: problem summaries and problem-solving exercises (tripartite problem-solving exercise) for the problem-based learning component and group tasks and individual exercises for the cultural issues. Self-selected groups chose specific tasks from a prescribed list of options (setting up a journal in molecular gastronomy, developing an electronic tongue, designing a restaurant for synesthetes, organizing a farmers' market, marketing a culinary tour, framing hedonic scales, exploring changing tastes through works of art or recipe books, and crafting beers for space travel). Individual tasks were selected from a menu of options (book reviews, film reviews, conversations, creative writing, and oral exams). A few guest lecturers (wine making, cultural anthropology, film analysis, and nutritional epidemiology) added more flavor. The course was rated highly for its learning value (8.5 ± 1.2, n = 62) and helped students relate biological mechanisms to cultural issues (9.0 ± 0.9, n = 62). Copyright © 2015 The American Physiological Society.

  16. A Human-Humanoid Interaction through the use of BCI for Locked-In ALS Patients using neuro-biological feedback fusion.

    Science.gov (United States)

    Sorbello, Rosario; Tramonte, Salvatore; Giardina, Marcello; La Bella, Vincenzo; Spataro, Rossella; Allison, Brendan; Guger, Christoph; Chella, Antonio

    2017-07-18

    This paper illustrates a new architecture for a human-humanoid interaction based on EEG-Brain Computer Interface (EEG-BCI) for patients affected by locked-in syndrome caused by Amyotrophic Lateral Sclerosis (ALS). The proposed architecture is able to recognise users' mental state accordingly to the biofeedback factor Bf , based on users' Attention, Intention and Focus, that is used to elicit a robot to perform customised behaviours. Experiments have been conducted with a population of 8 subjects: 4 ALS patients in a near Locked-in status with normal ocular movement and 4 healthy control subjects enrolled for age, education and computer expertise. The results showed as three ALS patients have completed the task with 96.67% success; the healthy controls with 100% success; the fourth ALS has been excluded from the results for his low general attention during the task; the analysis of Bf factor highlights as ALS subjects have shown stronger Bf (81.20%) than healthy controls (76.77%). Finally, a post-hoc analysis is provided to show how robotic feedback helps in maintaining focus on expected task. These preliminary data suggest that ALS patients could successfully control a humanoid robot through a BCI architecture, potentially enabling them to conduct some everyday tasks and extend their presence in the environment.

  17. [Actively promote the development of neuro-ophthalmology in China].

    Science.gov (United States)

    Wei, Shi-hui; Zhao, Jia-liang

    2010-12-01

    Neuro-ophthalmology is a medical subspecialty concerned on the nervous system diseases with ocular manifestations, this could be both sensory and motor, including ocular movements, papillary responses, and the structure changes of the brain and nervous system with ocular manifestations. Although neuro-ophthalmology in China has achieved some progress, certain problems still exist, such as the professional neuro-ophthalmology team and related academic organization are still absent in China; neuro-ophthalmology knowledge has not been popularized; the new technologies for diagnosis and treatment in neuro-ophthalmology have not been absorbed and applied; the coordination and cooperation with other related disciplines are not enough. We should actively promote the development of neuro-ophthalmology in China, including organization of a professional team of neuro-ophthalmology, popularization of neuro-ophthalmology knowledge to the ophthalmologists, development of research work in neuro-ophthalmology and the collaboration with international neuro-ophthalmologists.

  18. Molecular clocks and the human condition: approaching their characterization in human physiology and disease.

    Science.gov (United States)

    Fitzgerald, G A; Yang, G; Paschos, G K; Liang, X; Skarke, C

    2015-09-01

    Molecular clockworks knit together diverse biological networks and compelling evidence from model systems infers their importance in metabolism, immunological and cardiovascular function. Despite this and the diurnal variation in many aspects of human physiology and the phenotypic expression of disease, our understanding of the role and importance of clock function and dysfunction in humans is modest. There are tantalizing hints of connection across the translational divide and some correlative evidence of gene variation and human disease but most of what we know derives from forced desynchrony protocols in controlled environments. We now have the ability to monitor quantitatively ex vivo or in vivo the genome, metabolome, proteome and microbiome of humans in the wild. Combining this capability, with the power of mobile telephony and the evolution of remote sensing, affords a new opportunity for deep phenotyping, including the characterization of diurnal behaviour and the assessment of the impact of the clock on approved drug function. © 2015 John Wiley & Sons Ltd.

  19. Foods: Where Innovation, Agriculture, Molecular Biosciences and Human Nutrition Meet

    Directory of Open Access Journals (Sweden)

    Charles Brennan

    2012-11-01

    Full Text Available There is one commodity the world over that unites mankind—food. In 2011 the United Nations claimed that the world’s population had reached the seven billion mark, a number which is set to increase dramatically in the decades to come. Food security, supply and sustainability are of paramount concern to the future economic and social progress of humanity. It is the responsibility of the food industry, together with food scientists and technologists, to shoulder the burden of ensuring an adequate supply of nutritious, safe and sensorially acceptable foods for a range of demanding consumers. In responding to this challenge, we need to understand the link between agriculture, engineering, food processing, molecular biosciences, human nutrition, commercialisation and innovation. Access to information concerning the composition and quality of foods has never been so easy for consumers and technologists alike. A plethora of research publications are made available each month to scientists and associated interested parties. The outcomes of these research manuscripts are often distilled and disseminated into messages available to everyone through bulletin boards, forums and the popular press. Newspapers and new agencies constantly report on the latest pharma-medical finding, or news regarding food safety and security concerns. We live in an age where information is so readily available to everyone that the task of finding credible and reputable data can be difficult at times. Providing sound evidenced based research is where a peer-reviewed journal can provide clarity. [...

  20. Immunohistochemical and molecular characterization of the human periosteum.

    Science.gov (United States)

    Frey, Sönke Percy; Jansen, Hendrik; Doht, Stefanie; Filgueira, Luis; Zellweger, Rene

    2013-01-01

    The aim of the present study was to characterize the cell of the human periosteum using immunohistological and molecular methods. Phenotypic properties and the distribution of the cells within the different layers were investigated with immunohistochemical staining techniques and RT-PCR, focussing on markers for stromal stem cells, osteoblasts, osteoclasts and immune cells. Immunohistochemical results revealed that all stained cells were located in the cambium layer and that most cells were positive for vimentin. The majority of cells consisted of stromal stem cells and osteoblastic precursor cells. The density increased towards the deeper layers of the cambium. In addition, cells positive for markers of the osteoblast, chondrocyte, and osteoclast lineages were found. Interestingly, there were MHC class II-expressing immune cells suggesting the presence of dendritic cells. Using lineage-specific primer pairs RT-PCR confirmed the immunofluorescence microscopy results, supporting that human periosteum serves as a reservoir of stromal stem cells, as well as cells of the osteoblastic, and the chondroblastic lineage, osteoclasts, and dendritic cells. Our work elucidates the role of periosteum as a source of cells with a high regenerative capacity. Undifferentiated stromal stem cells as well as osteoblastic precursor cells are dominating in the cambium layer. A new outlook is given towards an immune response coming from the periosteum as MHC II positive immune cells were detected.

  1. Molecular vibration-sensing component in human olfaction.

    Directory of Open Access Journals (Sweden)

    Simon Gane

    Full Text Available Whether olfaction recognizes odorants by their shape, their molecular vibrations, or both remains an open and controversial question. A convenient way to address it is to test for odor character differences between deuterated and undeuterated odorant isotopomers, since these have identical ground-state conformations but different vibrational modes. In a previous paper (Franco et al. (2011 Proc Natl Acad Sci USA 108:9, 3797-802 we showed that fruit flies can recognize the presence of deuterium in odorants by a vibrational mechanism. Here we address the question of whether humans too can distinguish deuterated and undeuterated odorants. A previous report (Keller and Vosshall (2004 Nat Neurosci 7:4, 337-8 indicated that naive subjects are incapable of distinguishing acetophenone and d-8 acetophenone. Here we confirm and extend those results to trained subjects and gas-chromatography [GC]-pure odorants. However, we also show that subjects easily distinguish deuterated and undeuterated musk odorants purified to GC-pure standard. These results are consistent with a vibrational component in human olfaction.

  2. Human fertility, molecular genetics, and natural selection in modern societies.

    Directory of Open Access Journals (Sweden)

    Felix C Tropf

    Full Text Available Research on genetic influences on human fertility outcomes such as number of children ever born (NEB or the age at first childbirth (AFB has been solely based on twin and family-designs that suffer from problematic assumptions and practical limitations. The current study exploits recent advances in the field of molecular genetics by applying the genomic-relationship-matrix based restricted maximum likelihood (GREML methods to quantify for the first time the extent to which common genetic variants influence the NEB and the AFB of women. Using data from the UK and the Netherlands (N = 6,758, results show significant additive genetic effects on both traits explaining 10% (SE = 5 of the variance in the NEB and 15% (SE = 4 in the AFB. We further find a significant negative genetic correlation between AFB and NEB in the pooled sample of -0.62 (SE = 0.27, p-value = 0.02. This finding implies that individuals with genetic predispositions for an earlier AFB had a reproductive advantage and that natural selection operated not only in historical, but also in contemporary populations. The observed postponement in the AFB across the past century in Europe contrasts with these findings, suggesting an evolutionary override by environmental effects and underscoring that evolutionary predictions in modern human societies are not straight forward. It emphasizes the necessity for an integrative research design from the fields of genetics and social sciences in order to understand and predict fertility outcomes. Finally, our results suggest that we may be able to find genetic variants associated with human fertility when conducting GWAS-meta analyses with sufficient sample size.

  3. Human fertility, molecular genetics, and natural selection in modern societies.

    Science.gov (United States)

    Tropf, Felix C; Stulp, Gert; Barban, Nicola; Visscher, Peter M; Yang, Jian; Snieder, Harold; Mills, Melinda C

    2015-01-01

    Research on genetic influences on human fertility outcomes such as number of children ever born (NEB) or the age at first childbirth (AFB) has been solely based on twin and family-designs that suffer from problematic assumptions and practical limitations. The current study exploits recent advances in the field of molecular genetics by applying the genomic-relationship-matrix based restricted maximum likelihood (GREML) methods to quantify for the first time the extent to which common genetic variants influence the NEB and the AFB of women. Using data from the UK and the Netherlands (N = 6,758), results show significant additive genetic effects on both traits explaining 10% (SE = 5) of the variance in the NEB and 15% (SE = 4) in the AFB. We further find a significant negative genetic correlation between AFB and NEB in the pooled sample of -0.62 (SE = 0.27, p-value = 0.02). This finding implies that individuals with genetic predispositions for an earlier AFB had a reproductive advantage and that natural selection operated not only in historical, but also in contemporary populations. The observed postponement in the AFB across the past century in Europe contrasts with these findings, suggesting an evolutionary override by environmental effects and underscoring that evolutionary predictions in modern human societies are not straight forward. It emphasizes the necessity for an integrative research design from the fields of genetics and social sciences in order to understand and predict fertility outcomes. Finally, our results suggest that we may be able to find genetic variants associated with human fertility when conducting GWAS-meta analyses with sufficient sample size.

  4. Gene Expression and Functional Annotation of the Human Ciliary Body Epithelia

    NARCIS (Netherlands)

    S.F. Janssen (Sarah); T.G.M.F. Gorgels (Theo); K. Bossers (Koen); J.B. ten Brink (Jacoline); A.H.W. Essing (Anke); M.H. Nagtegaal (Marleen); P.J. van der Spek (Peter); N.M. Jansonius (Nomdo); A.A.B. Bergen (Arthur)

    2012-01-01

    textabstractPurpose: The ciliary body (CB) of the human eye consists of the non-pigmented (NPE) and pigmented (PE) neuro-epithelia. We investigated the gene expression of NPE and PE, to shed light on the molecular mechanisms underlying the most important functions of the CB. We also developed

  5. Optimization of Neuro-Fuzzy System

    Directory of Open Access Journals (Sweden)

    M. Sarosa

    2007-05-01

    Full Text Available Neuro-fuzzy system has been shown to provide a good performance on chromosome classification but does not offer a simple method to obtain the accurate parameter values required to yield the best recognition rate. This paper presents a neuro-fuzzy system where its parameters can be automatically adjusted using genetic algorithms. The approach combines the advantages of fuzzy logic theory, neural networks, and genetic algorithms. The structure consists of a four layer feed-forward neural network that uses a GBell membership function as the output function. The proposed methodology has been applied and tested on banded chromosome classification from the Copenhagen Chromosome Database. Simulation result showed that the proposed neuro-fuzzy system optimized by genetic algorithms offers advantages in setting the parameter values, improves the recognition rate significantly and decreases the training/testing time which makes genetic neuro-fuzzy system suitable for chromosome classification.

  6. Society of NeuroInterventional Surgery

    Science.gov (United States)

    ... NeuroInterventional Surgery is dedicated to excellence in comprehensive, minimally-invasive care of patients with stroke, brain aneurysms, and other diseases in the head, neck and spine. In the Spotlight Physicians Call on States to ...

  7. NEURO-VASCULAR INJURIES ASSOCIATED WITH LIMB ...

    African Journals Online (AJOL)

    hi-tech

    2000-12-01

    Dec 1, 2000 ... Results: Road traffic accidents were the main cause of fractures associated with neuro- vascular ... the patients with vascular or nerve injury associated with fractures .... of traumatic aorto-iliac dissection injury in a child with.

  8. Neuro-fuzzy modeling in bankruptcy prediction

    Directory of Open Access Journals (Sweden)

    Vlachos D.

    2003-01-01

    Full Text Available For the past 30 years the problem of bankruptcy prediction had been thoroughly studied. From the paper of Altman in 1968 to the recent papers in the '90s, the progress of prediction accuracy was not satisfactory. This paper investigates an alternative modeling of the system (firm, combining neural networks and fuzzy controllers, i.e. using neuro-fuzzy models. Classical modeling is based on mathematical models that describe the behavior of the firm under consideration. The main idea of fuzzy control, on the other hand, is to build a model of a human control expert who is capable of controlling the process without thinking in a mathematical model. This control expert specifies his control action in the form of linguistic rules. These control rules are translated into the framework of fuzzy set theory providing a calculus, which can stimulate the behavior of the control expert and enhance its performance. The accuracy of the model is studied using datasets from previous research papers.

  9. Molecular dynamics simulations for human CAR inverse agonists.

    Science.gov (United States)

    Jyrkkärinne, Johanna; Küblbeck, Jenni; Pulkkinen, Juha; Honkakoski, Paavo; Laatikainen, Reino; Poso, Antti; Laitinen, Tuomo

    2012-02-27

    Constitutive androstane receptor (CAR), along with pregnane x receptor (PXR), is an important metabolic sensor in the hepatocytes. Like all other nuclear receptors (NRs), CAR works in concert with coregulator proteins, coactivators, and corepressors which bind to the NRs. The main basis for the receptor to distinguish between coactivators and corepressors is the position of the C-terminal helix 12 (H12), which is determined by the bound NR ligand. CAR, having constitutive activity, can be repressed or further activated by its ligands. Crystal structure of human CAR bound to an agonist and a coactivator peptide is available, but no structural information on an inverse agonist-bound human CAR and a corepressor exists. In our previous molecular dynamics (MD) studies, no corepressor peptide was included. Therefore, probably due to the strong interactions which keep the relatively short H12 of CAR in the active position, the structural changes elicited by inverse agonists were very subtle, and H12 of CAR seemed to more or less retain its active conformation. Here, we have run a series of MD simulations to study the movement of H12 in the presence of both activating and repressing ligands as well as a corepressor peptide. The presence of the corepressor on the coregulator surface of CAR induced a clear shift of H12 of the inverse agonists-bound CAR. In general, H12 moved toward H10 and not away from the ligand binding domain, as seen in some other NRs. However, H12 of CAR is short enough that this movement seems to be adequate to accommodate the binding of the corepressor.

  10. Molecular Epidemiology of Human Norovirus in Korea in 2013

    Science.gov (United States)

    Kim, Jae-Seok; Hyun, Jungwon; Kim, Han-Sung; Song, Wonkeun

    2015-01-01

    Norovirus is a major cause of acute gastroenteritis. The molecular epidemiology of norovirus exhibits temporal and geographical fluctuations, and new variants of the GII.4 genotype emerge every 2-3 years to cause global epidemics of acute gastroenteritis. We investigated GI and GII genotypes of human norovirus strains isolated from patients with acute gastroenteritis in Korea in 2013. Norovirus antigen test was performed on 2,980 fecal specimens from January to December 2013. RNA was extracted from norovirus antigen-positive fecal suspensions, and the norovirus capsid (VP1) and polymerase (RdRp) genes were characterized by RT-PCR and sequencing. Of the 230 genotyped strains, GII.4 (77.3%) was the most frequently observed capsid genotype, followed by GII.3 (6.1%) and GII.13 (3.9%). A norovirus GII.4 variant, GII.Pe/GII.4 Sydney 2012, was the most frequently found polymerase/capsid genotype (65.7%), followed by GII.P17/GII.17 (2.1%) and GII.P21/GII.3 (2.1%). Phylogenetic, similarity, and capsid epitope analyses of GII.Pe/GII.4 Sydney 2012 strains were performed. We concluded that the norovirus GII.4 variant, GII.Pe/GII.4 Sydney 2012, was the main cause of norovirus-related gastroenteritis in Korea in 2013. PMID:26421289

  11. Lessons from molecular modeling human α-L-iduronidase.

    Science.gov (United States)

    Figueiredo, Danieli Forgiarini; Antunes, Dinler A; Rigo, Maurício M; Mendes, Marcus F A; Silva, Jader P; Mayer, Fabiana Q; Matte, Ursula; Giugliani, Roberto; Vieira, Gustavo F; Sinigaglia, Marialva

    2014-11-01

    Human α-L-iduronidase (IDUA) is a member of glycoside hydrolase family and is involved in the catabolism of glycosaminoglycans (GAGs), heparan sulfate (HS) and dermatan sulfate (DS). Mutations in this enzyme are responsible for mucopolysaccharidosis I (MPS I), an inherited lysosomal storage disorder. Despite great interest in determining and studying this enzyme structure, the lack of a high identity to templates and other technical issues have challenged both bioinformaticians and crystallographers, until the recent publication of an IDUA crystal structure (PDB: 4JXP). In the present work, four alternative IDUA models, generated and evaluated prior to crystallographic determination, were compared to the 4JXP structure. A combined analysis using several viability assessment tools and molecular dynamics simulations highlights the strengths and limitations of different comparative modeling protocols, all of which are based on the same low identity template (only 22%). Incorrect alignment between the target and template was confirmed to be a major bottleneck in homology modeling, regardless of the modeling software used. Moreover, secondary structure analysis during a 50ns simulation seems to be useful for indicating alignment errors and structural instabilities. The best model was achieved through the combined use of Phyre 2 and Modeller, suggesting the use of this protocol for the modeling of other proteins that still lack high identity templates. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Human protein reference database and human proteinpedia as discovery resources for molecular biotechnology.

    Science.gov (United States)

    Goel, Renu; Muthusamy, Babylakshmi; Pandey, Akhilesh; Prasad, T S Keshava

    2011-05-01

    In the recent years, research in molecular biotechnology has transformed from being small scale studies targeted at a single or a small set of molecule(s) into a combination of high throughput discovery platforms and extensive validations. Such a discovery platform provided an unbiased approach which resulted in the identification of several novel genetic and protein biomarkers. High throughput nature of these investigations coupled with higher sensitivity and specificity of Next Generation technologies provided qualitatively and quantitatively richer biological data. These developments have also revolutionized biological research and speed of data generation. However, it is becoming difficult for individual investigators to directly benefit from this data because they are not easily accessible. Data resources became necessary to assimilate, store and disseminate information that could allow future discoveries. We have developed two resources--Human Protein Reference Database (HPRD) and Human Proteinpedia, which integrate knowledge relevant to human proteins. A number of protein features including protein-protein interactions, post-translational modifications, subcellular localization, and tissue expression, which have been studied using different strategies were incorporated in these databases. Human Proteinpedia also provides a portal for community participation to annotate and share proteomic data and uses HPRD as the scaffold for data processing. Proteomic investigators can even share unpublished data in Human Proteinpedia, which provides a meaningful platform for data sharing. As proteomic information reflects a direct view of cellular systems, proteomics is expected to complement other areas of biology such as genomics, transcriptomics, molecular biology, cloning, and classical genetics in understanding the relationships among multiple facets of biological systems.

  13. Molecular interaction studies of trimethoxy flavone with human serum albumin.

    Directory of Open Access Journals (Sweden)

    Mahesh Gokara

    Full Text Available BACKGROUND: Human serum albumin (HSA is the most abundant protein in blood plasma, having high affinity binding sites for several endogenous and exogenous compounds. Trimethoxy flavone (TMF is a naturally occurring flavone isolated from Andrographis viscosula and used in the treatment of dyspepsia, influenza, malaria, respiratory functions and as an astringent and antidote for poisonous stings of some insects. METHODOLOGY/PRINCIPAL FINDINGS: The main aim of the experiment was to examine the interaction between TMF and HSA at physiological conditions. Upon addition of TMF to HSA, the fluorescence emission was quenched and the binding constant of TMF with HSA was found to be K(TMF = 1.0+/-0.01x10(3 M(-1, which corresponds to -5.4 kcal M(-1 of free energy. Micro-TOF Q mass spectrometry results showed a mass increase of from 66,513 Da (free HSA to 66,823 Da (HAS +Drug, indicating the strong binding of TMF with HSA resulting in decrease of fluorescence. The HSA conformation was altered upon binding of TMF to HSA with decrease in alpha-helix and an increase in beta-sheets and random coils suggesting partial unfolding of protein secondary structure. Molecular docking experiments found that TMF binds strongly with HSA at IIIA domain of hydrophobic pocket with hydrogen bond and hydrophobic interactions. Among which two hydrogen bonds are formed between O (19 of TMF to Arg 410, Tyr 411 and another one from O (7 of TMF to Asn 391, with bond distance of 2.1 A, 3.6 A and 2.6 A, respectively. CONCLUSIONS/SIGNIFICANCE: In view of the evidence presented, it is imperative to assign a greater role of HSA's as a carrier molecule for many drugs to understand the interactions of HSA with TMF will be pivotal in the design of new TMF-inspired drugs.

  14. The NeuroDevNet vision.

    Science.gov (United States)

    Goldowitz, Dan; McArthur, Dawn

    2011-03-01

    The NeuroDevNet Network of Centres of Excellence has created the first trans-Canada effort devoted to the study of brain development from basic to clinical to societal perspectives. NeuroDevNet's vision is to accelerate efforts to (i) understand normal brain development; (ii) enhance our ability to make diagnoses of when normal development goes awry; and (iii) develop interventions to improve or prevent neurodevelopmental disorders. An early diagnosis coupled with the right therapies, The NeuroDevNet Network of Centres of Excellence has created the first trans-Canada effort devoted to the study of brain development from basic to clinical to societal perspectives. NeuroDevNet's vision is to accelerate efforts to (i) understand normal brain development; (ii) enhance our ability to make diagnoses of when normal development goes awry; and (iii) develop interventions to improve or prevent neurodevelopmental disorders. An early diagnosis coupled with the right therapies, Demonstration Projects. Funds were also allocated for an Opportunities Initiative. There is a wide of expertise amongst NeuroDevNet members. Researchers are supported by the management centre, three Platforms (Imaging; Genetics/ Epigenetics; Animal Models) and three Cores (Neuroethics; Neuroinformatics; Knowledge Translation). We emphasize multidisciplinary training of young researchers to advance the understanding of brain disorders that affect children. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. The Danish Neuro-Oncology Registry

    DEFF Research Database (Denmark)

    Hansen, Steinbjørn

    2016-01-01

    advantage of reporting indicators is the related multidisciplinary discussions giving a better understanding of what actually is going on, thereby facilitating the work on adjusting the national guidelines in the Danish Neuro-Oncology Group. CONCLUSION: The establishment of DNOR has optimized the quality...... in handling primary brain tumor patients in Denmark by reporting indicators and facilitating a better multidisciplinary collaboration at a national level. DNOR provides a valuable resource for research.......AIM OF DATABASE: The Danish Neuro-Oncology Registry (DNOR) was established by the Danish Neuro-Oncology Group as a national clinical database. It was established for the purpose of supporting research and development in adult patients with primary brain tumors in Denmark. STUDY POPULATION: DNOR has...

  16. THE PROGRAMMING NEURO-LINGUISTICS AND THEIR APPLICABILITY IN THE PROCESS OF RECRUITMENT AND SELECTION

    Directory of Open Access Journals (Sweden)

    Gilma Álamo Sánchez

    2008-04-01

    Full Text Available He/she is carried out a study referred to tools of Programming Neuro-linguistics (PNL for the Selection, Employment and Training that allow choosing the appropriate personnel taking the language and the behavior as a result. For their development theories were revised referred to the PNL and the recruitment process and selection sustained in the process of the interview. The summations are oriented to the importance and convenience for the Management of Human resources of applying the Programming Neuro-linguistics as selection tool of personal. Finally it is recommended to apply the proposal inside the mark of adaptability according to the necessities and demands of each organization.

  17. VLSI design of universal approximator neuro-fuzzy systems

    OpenAIRE

    Baturone, I.; Sánchez-Solano, Santiago; Barriga, Angel; Jiménez Fernández, Carlos Jesús; Senhadji, Raouf; López, D. R.

    2001-01-01

    Neuro-fuzzy systems can theoretically solve any problem since they are universal approximators. Besides, they combine the advantages of the neuro and fuzzy paradigms. This paper describes and compares the different strategies that can be adopted to implement the learning and inference mechanisms involved in a neuro-fuzzy system. CAD tools, most of them integrated into the fuzzy system development environment Xfuzzy 2.0, have been developed to assist the designer in the implementation of neuro...

  18. Molecular characterization of the human microbiome from a reproductive perspective

    National Research Council Canada - National Science Library

    Mor, Amir; Driggers, Paul H; Segars, James H

    2015-01-01

    ... and individuals from harmful microbes during the process. Advances in molecular biology techniques have expanded our understanding of the natural organisms living on and in our bodies, including those inhabiting the reproductive tract...

  19. Treatment of neuro-ophthalmic sarcoidosis.

    Science.gov (United States)

    Frohman, Larry P

    2015-03-01

    Because of the rarity of neuro-ophthalmic sarcoidosis, there are no therapeutic guidelines based on evidence-based medicine for this disorder. Review of literature combined with personal experience. Corticosteroids are the preferred initial therapy for neuro-ophthalmic sarcoidosis. If patients cannot tolerate the requisite dose of corticosteroid needed to control their disease, or if corticosteroids fail to adequately control the disease process, the choices of a second agent are based on the consideration of rapidity of clinical response and the safety profile. Although methotrexate and mycophenolate mofetil are the medications that are often selected after corticosteroid failure, more rapidly acting agents that have been used are infliximab and intravenous cyclophosphamide.

  20. Molecular phylogeny of anoplocephalid tapeworms (Cestoda: Anoplocephalidae) infecting humans and non-human primates.

    Science.gov (United States)

    Doležalová, Jana; Vallo, Peter; Petrželková, Klára J; Foitová, Ivona; Nurcahyo, Wisnu; Mudakikwa, Antoine; Hashimoto, Chie; Jirků, Milan; Lukeš, Julius; Scholz, Tomáš; Modrý, David

    2015-09-01

    Anoplocephalid tapeworms of the genus Bertiella Stiles and Hassall, 1902 and Anoplocephala Blanchard, 1848, found in the Asian, African and American non-human primates are presumed to sporadic ape-to-man transmissions. Variable nuclear (5.8S-ITS2; 28S rRNA) and mitochondrial genes (cox1; nad1) of isolates of anoplocephalids originating from different primates (Callicebus oenanthe, Gorilla beringei, Gorilla gorilla, Pan troglodytes and Pongo abelii) and humans from various regions (South America, Africa, South-East Asia) were sequenced. In most analyses, Bertiella formed a monophyletic group within the subfamily Anoplocephalinae, however, the 28S rRNA sequence-based analysis indicated paraphyletic relationship between Bertiella from primates and Australian marsupials and rodents, which should thus be regarded as different taxa. Moreover, isolate determined as Anoplocephala cf. gorillae from mountain gorilla clustered within the Bertiella clade from primates. This either indicates that A. gorillae deserves to be included into the genus Bertiella, or, that an unknown Bertiella species infects also mountain gorillas. The analyses allowed the genetic differentiation of the isolates, albeit with no obvious geographical or host-related patterns. The unexpected genetic diversity of the isolates studied suggests the existence of several Bertiella species in primates and human and calls for revision of the whole group, based both on molecular and morphological data.

  1. From ‘Hard’ Neuro-Tools to ‘Soft’ Neuro-Toys? : Refocussing the Neuro-Enhancement Debate

    NARCIS (Netherlands)

    Brenninkmeijer, Jonna; Zwart, Hub

    2016-01-01

    Since the 1990’s, the debate concerning the ethical, legal and societal aspects of ‘neuro-enhancement’ has evolved into a massive discourse, both in the public realm and in the academic arena. This ethical debate, however, tends to repeat the same sets of arguments over and over again. Normative

  2. Molecular aging and rejuvenation of human muscle stem cells

    OpenAIRE

    Carlson, Morgan E; Suetta, Charlotte; Conboy, Michael J.; Aagaard, Per; Mackey, Abigail; Kjaer, Michael; Conboy, Irina

    2009-01-01

    Very little remains known about the regulation of human organ stem cells (in general, and during the aging process), and most previous data were collected in short-lived rodents. We examined whether stem cell aging in rodents could be extrapolated to genetically and environmentally variable humans. Our findings establish key evolutionarily conserved mechanisms of human stem cell aging. We find that satellite cells are maintained in aged human skeletal muscle, but fail to activate in response ...

  3. The Effects of Water Matrix on Decay of Human Fecal Molecular Markers and Campylobacter spp.

    Science.gov (United States)

    Although molecular source tracking for human fecal contamination is used on a wide range of sample types, little is known about comparative decay of proposed molecular markers under different conditions, or correlation with pathogen decay. Our purpose was to measure correlations ...

  4. Molecular consequences of psychological stress in human aging.

    Science.gov (United States)

    Moreno-Villanueva, M; Bürkle, A

    2015-08-01

    Psychological stress has often been described as a feeling of being overwhelmed by the necessity of constant adjustment to an individual's changing environment. Stress affects people of all ages, but the lives of the elderly may particularly be affected. Major changes can cause anxiety leading to feelings of insecurity and/or loss of self-esteem and depression. The cellular mechanisms underlying psychological stress are poorly understood. This review focuses on the physical and molecular consequences of psychological stress linked to aging processes and, in particular, how molecular changes induced by psychological stress can compromise healthy aging. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Molecular Detection of Diphyllobothrium nihonkaiense in Humans, China

    Science.gov (United States)

    Chen, Shanhong; Ai, Lin; Zhang, Yongnian; Chen, Jiaxu; Zhang, Weizhe; Li, Yihong; Muto, Maki; Morishima, Yasuyuki; Sugiyama, Hiromu; Xu, Xuenian; Zhou, Xiaonong

    2014-01-01

    The cause of diphyllobothriosis in 5 persons in Harbin and Shanghai, China, during 2008–2011, initially attributed to the tapeworm Diphyllobothrium latum, was confirmed as D. nihonkaiense by using molecular analysis of expelled proglottids. The use of morphologic characteristics alone to identify this organism was inadequate and led to misidentification of the species. PMID:24447495

  6. Molecular typing of fecal eukaryotic microbiota of human infants and ...

    Indian Academy of Sciences (India)

    Keywords. 18S rRNA library; gastrointestinal tract; micro-eukaryotic diversity ... Insect Molecular Biology Unit, National Centre for Cell Science, Pune University Campus, Ganeshkhind, Pune 411 007, Maharashtra, India; Gastroenterology Unit, Department of P ediatrics, KEM Hospital, Rasta Peth, Pune 411 011, India ...

  7. Molecular characterization of bacterial communities in the human gastrointestinal tract

    NARCIS (Netherlands)

    Zoetendal, E.G.

    2001-01-01

    The human gastrointestinal (GI) tract is a complex ecosystem in which host and microbial cells live in close contact with each other. The microbial community in the human GI tract has an important nutritional and protective function and mainly consists of anaerobic bacteria. After birth,

  8. An Exercise in Molecular Epidemiology: Human Rhinovirus Prevalence and Genetics

    Science.gov (United States)

    Albright, Catherine J.; Hall, David J.

    2011-01-01

    Human rhinovirus (HRV) is one of the most common human respiratory pathogens and is responsible for the majority of upper respiratory illnesses. Recently, a phylogeny was constructed from all known American Type Culture Collection (ATCC) HRV sequences. From this study, three HRV classifications (HRVA, HRVB, and HRVC) were determined and techniques…

  9. Molecular cloning and characterization of a novel human kinase ...

    Indian Academy of Sciences (India)

    Ensembl Genome Browser located PDIK1L to human chromosome 1p35.3. It spans about 13.7 kb and consists of four exons and three introns. Multiple-tissue cDNA panel PCR revealed that the gene is expressed widely in human tissues: liver, kidney, pancreas, spleen, thymus and prostate. The protein appears to be ...

  10. The NeuroDevNet Autism Spectrum Disorders Demonstration Project.

    Science.gov (United States)

    Zwaigenbaum, Lonnie; Scherer, Stephen; Szatmari, Peter; Fombonne, Eric; Bryson, Susan E; Hyde, Krista; Anagnostou, Evdokia; Anognostou, Evdokia; Brian, Jessica; Evans, Alan; Hall, Geoff; Nicholas, David; Roberts, Wendy; Smith, Isabel; Vaillancourt, Tracy; Volden, Joanne

    2011-03-01

    The NeuroDevNet Autism Spectrum Disorder Demonstration Project interfaces at many levels with the network's research themes and priorities. Our interdisciplinary team aims to improve understanding of genetic factors underlying vulnerability to autism spectrum disorders (ASDs) to develop better diagnostic strategies and, ultimately, to pinpoint molecular pathways relevant to developing biologically based treatments. Linking our existing longitudinal ASD cohorts with both genetics and neuroimaging studies will provide, for the first time, integrated data on how the genetic variation influences brain and behavioral development in ASD. Importantly, as our science progresses and we translate this information to the health care system, we will also educate policy makers, media, and business, so an informed society is prepared to capitalize on new genomic advances and effectively integrate these into health services for the broader community. We believe that this research has the potential to transform assessment and care for individuals with ASD. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Polyacrylamide gels with selective recognition of the tetrameric molecular form of human growth hormone

    Directory of Open Access Journals (Sweden)

    R. Kublickas

    2017-08-01

    Full Text Available Networks of polyacrylamide were studied for the possibility of imprinting of the oligomeric form of human growth hormone. The tetrameric molecular form of human growth hormone was molecularly imprinted for the first time. The results show that approximately 50–70% (w/w of the templates (depending on polymerization conditions could be extracted from the molecularly imprinted acrylamide polymers. The resulting ‘gel antibodies’ against this form of human growth hormone in the form of granules of polyacrylamide were compared with granules of non-imprinted polymer. The selectivity of the artificial gel antibodies was studied. Investigation of the binding to imprinted polymer of the template hormone, other molecular forms of the hormone and other proteins shows the selectivity of the developed artificial gel antibodies.

  12. Molecular epidemiology and evolution of human respiratory syncytial virus and human metapneumovirus.

    Directory of Open Access Journals (Sweden)

    Eleanor R Gaunt

    2011-03-01

    Full Text Available Human respiratory syncytial virus (HRSV and human metapneumovirus (HMPV are ubiquitous respiratory pathogens of the Pneumovirinae subfamily of the Paramyxoviridae. Two major surface antigens are expressed by both viruses; the highly conserved fusion (F protein, and the extremely diverse attachment (G glycoprotein. Both viruses comprise two genetic groups, A and B. Circulation frequencies of the two genetic groups fluctuate for both viruses, giving rise to frequently observed switching of the predominantly circulating group. Nucleotide sequence data for the F and G gene regions of HRSV and HMPV variants from the UK, The Netherlands, Bangkok and data available from Genbank were used to identify clades of both viruses. Several contemporary circulating clades of HRSV and HMPV were identified by phylogenetic reconstructions. The molecular epidemiology and evolutionary dynamics of clades were modelled in parallel. Times of origin were determined and positively selected sites were identified. Sustained circulation of contemporary clades of both viruses for decades and their global dissemination demonstrated that switching of the predominant genetic group did not arise through the emergence of novel lineages each respiratory season, but through the fluctuating circulation frequencies of pre-existing lineages which undergo proliferative and eclipse phases. An abundance of sites were identified as positively selected within the G protein but not the F protein of both viruses. For HRSV, these were discordant with previously identified residues under selection, suggesting the virus can evade immune responses by generating diversity at multiple sites within linear epitopes. For both viruses, different sites were identified as positively selected between genetic groups.

  13. Molecular principles of human virus protein-protein interactions.

    Science.gov (United States)

    Halehalli, Rachita Ramachandra; Nagarajaram, Hampapathalu Adimurthy

    2015-04-01

    Viruses, from the human protein-protein interaction network perspective, target hubs, bottlenecks and interconnected nodes enriched in certain biological pathways. However, not much is known about the general characteristic features of the human proteins interacting with viral proteins (referred to as hVIPs) as well as the motifs and domains utilized by human-virus protein-protein interactions (referred to as Hu-Vir PPIs). Our study has revealed that hVIPs are mostly disordered proteins, whereas viral proteins are mostly ordered proteins. Protein disorder in viral proteins and hVIPs varies from one subcellular location to another. In any given viral-human PPI pair, at least one of the two proteins is structurally disordered suggesting that disorder associated conformational flexibility as one of the characteristic features of virus-host interaction. Further analyses reveal that hVIPs are (i) slowly evolving proteins, (ii) associated with high centrality scores in human-PPI network, (iii) involved in multiple pathways, (iv) enriched in eukaryotic linear motifs (ELMs) associated with protein modification, degradation and regulatory processes, (v) associated with high number of splice variants and (vi) expressed abundantly across multiple tissues. These aforementioned findings suggest that conformational flexibility, spatial diversity, abundance and slow evolution are the characteristic features of the human proteins targeted by viral proteins. Hu-Vir PPIs are mostly mediated via domain-motif interactions (DMIs) where viral proteins employ motifs that mimic host ELMs to bind to domains in human proteins. DMIs are shared among viruses belonging to different families indicating a possible convergent evolution of these motifs to help viruses to adopt common strategies to subvert host cellular pathways. Hu-Vir PPI data, DDI and DMI data for human-virus PPI can be downloaded from http://cdfd.org.in/labpages/computational_biology_datasets.html. Supplementary data are

  14. THE MOLECULAR MECHANISMS OF EPSTEINBARR VIRUS PERSISTENCE IN THE HUMAN ORGANISM

    OpenAIRE

    Volyanskiy A.Yu; Kolotova T.Yu; Romanova E. A.; Sidorenko T.A.; Igumnova N.I.; Konoreva E.S.; Yukhimenko V.I; Kabluchko T.V.; Pogorila M.S.

    2014-01-01

    This review describes advances in molecular aspects of EBV infection and disease. We discuss the spectrum of clinical illness due to EBV persistent infection. The main characteristic of Epstein-Barr virus (EBV) is that initial infection results in lifelong persistence. EBV infects nearly all humans by the time they reach adulthood. Healthy humans have approximately 1 to 50 infected cells per million leukocytes. EBV is one of the eight known human herpesviruses. EBV vir...

  15. Neuro-Semantics and Semantics.

    Science.gov (United States)

    Holmes, Stewart W.

    1987-01-01

    Draws distinctions between the terms semantics (dealing with such verbal parameters as dictionaries and "laws" of logic and rhetoric), general semantics (semantics, plus the complex, dynamic, organismal properties of human beings and their physical environment), and neurosemantics (names for relations-based input from the neurosensory…

  16. A Trio of Human Molecular Genetics PCR Assays

    Science.gov (United States)

    Reinking, Jeffrey L.; Waldo, Jennifer T.; Dinsmore, Jannett

    2013-01-01

    This laboratory exercise demonstrates three different analytical forms of the polymerase chain reaction (PCR) that allow students to genotype themselves at four different loci. Here, we present protocols to allow students to a) genotype a non-coding polymorphic Variable Number of Tandem Repeat (VNTR) locus on human chromosome 5 using conventional…

  17. Molecular cloning of human dendritic cell associated lectin-1 ...

    African Journals Online (AJOL)

    The human Dectin-1 molecule known as a β-glucan receptor is an immune cell surface receptor implicated in the immunological defense against fungal and other pathogens. Dectin-1 is a type II transmemebrane receptor with a single extracellular carbohydrate recognition domain (CRD), a stalk region which separates the ...

  18. Molecular cloning of the human excision repair gene ERCC-6.

    NARCIS (Netherlands)

    C. Troelstra (Christine); H. Odijk (Hanny); J. de Wit (Jan); A. Westerveld (Andries); L.H. Thompson; D. Bootsma (Dirk); J.H.J. Hoeijmakers (Jan)

    1990-01-01

    textabstractThe UV-sensitive, nucleotide excision repair-deficient Chinese hamster mutant cell line UV61 was used to identify and clone a correcting human gene, ERCC-6. UV61, belonging to rodent complementation group 6, is only moderately UV sensitive in comparison with mutant lines in groups 1 to

  19. Human Fertility, Molecular Genetics, and Natural Selection in Modern Societies

    NARCIS (Netherlands)

    Tropf, Felix C.; Stulp, Gert; Barban, Nicola; Visscher, Peter M.; Yang, Jian; Snieder, Harold; Mills, Melinda C.

    2015-01-01

    Research on genetic influences on human fertility outcomes such as number of children ever born (NEB) or the age at first childbirth (AFB) has been solely based on twin and family-designs that suffer from problematic assumptions and practical limitations. The current study exploits recent advances

  20. Neuro-oncology of CNS tumors

    Energy Technology Data Exchange (ETDEWEB)

    Tonn, J.C. [Klinikum Grosshadern, Muenchen (Germany). Dept. of Neurosurgery; Westphal, M. [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Neurochirurgische Klinik; Rutka, J.T. [Toronto Univ. Hospital for Sick Children, ON (Canada). Div. of Neurosurgery; Grossmann, S.A. (eds.) [Johns Hopkins Oncology Center Neuro-Oncology, Baltimore, MD (United States)

    2006-07-01

    Diagnosis and treatment modalities for neuro-oncologic diseases have made considerable advances in recent years. There is hardly a segment of the field of solid tumours that is experiencing such dynamic development with regard to basic scientific findings and clinical results. In the present book the world's leading experts have compiled the current practice-relevant knowledge of neuro-oncologic diseases. The book's clear structure and the uniform presentation of all chapters make this volume a valuable reference, especially for practice-oriented activities, allowing swift access to information about current treatment standards. Hence it will be of great value to both clinicians and researchers. (orig.)

  1. A Multivariate Approach to Functional Neuro Modeling

    DEFF Research Database (Denmark)

    Mørch, Niels J.S.

    1998-01-01

    exists. - Model visualization and interpretation techniques. The simplicity of this task for linear models contrasts the difficulties involved when dealing with nonlinear models. Finally, a visualization technique for nonlinear models is proposed. A single observation emerges from the thesis......This Ph.D. thesis, A Multivariate Approach to Functional Neuro Modeling, deals with the analysis and modeling of data from functional neuro imaging experiments. A multivariate dataset description is provided which facilitates efficient representation of typical datasets and, more importantly......, provides the basis for a generalization theoretical framework relating model performance to model complexity and dataset size. Briefly summarized the major topics discussed in the thesis include: - An introduction of the representation of functional datasets by pairs of neuronal activity patterns...

  2. Mice with conditional NeuroD1 knockout display reduced aberrant hippocampal neurogenesis but no change in epileptic seizures.

    Science.gov (United States)

    Brulet, Rebecca; Zhu, Jingfei; Aktar, Mahafuza; Hsieh, Jenny; Cho, Kyung-Ok

    2017-07-01

    Adult neurogenesis is significantly increased in the hippocampus of rodent models of temporal lobe epilepsy (TLE). These adult-generated neurons have recently been shown to play a contributing role in the development of spontaneous recurrent seizures (SRS). In order to eventually target pro-epileptic adult neurogenesis in the clinical setting, it will be important to identify molecular players involved in the control of aberrant neurogenesis after seizures. Here, we focused on NeuroD1 (ND1), a member of the bHLH family of transcription factors previously shown to play an essential role in the differentiation and maturation of adult-generated neurons in the hippocampus. Wild-type mice treated with pilocarpine to induce status epilepticus (SE) showed a significant up-regulation of NeuroD1+ immature neuroblasts located in both the granule cell layer (GCL), and ectopically localized to the hilar region of the hippocampus. As expected, conditional knockout (cKO) of NeuroD1 in Nestin-expressing stem/progenitors and their progeny led to a reduction in the number of NeuroD1+ adult-generated neurons after pilocarpine treatment compared to WT littermates. Surprisingly, there was no change in SRS in NeuroD1 cKO mice, suggesting that NeuroD1 cKO fails to reduce aberrant neurogenesis below the threshold needed to impact SRS. Consistent with this conclusion, the total number of adult-generated neurons in the pilocarpine model, especially the total number of Prox1+ hilar ectopic granule cells were unchanged after NeuroD1 cKO, suggesting strategies to reduce SRS will need to achieve a greater removal of aberrant adult-generated neurons. Published by Elsevier Inc.

  3. Neuro-imaging in Patients Referred to a Neuro-ophthalmology Service: The Rates of Appropriateness and Concordance in Interpretation

    Science.gov (United States)

    McClelland, Collin; Van Stavern, Gregory P.; Shepherd, J. Banks; Gordon, Mae; Huecker, Julia

    2012-01-01

    Objective Neuro-imaging studies are frequently ordered to investigate neuro-ophthalmic symptoms. When misused these studies are expensive and time-consuming. This study aimed to describe the type and frequency of neuro-imaging errors in patients referred to an academic neuro-ophthalmology service and to measure how frequently these neuro-imaging studies were re-interpreted. Design Prospective cohort study Participants 84 consecutive patients referred to an academic neuro-ophthalmology practice Methods From November 2009 through July 2010 we prospectively enrolled 84 consecutive new patients who had received a neuro-imaging study in the last 12 months specifically in evaluation of their presenting neuro-ophthalmic symptoms. Participants then underwent a complete neuro-ophthalmic evaluation followed by a review of prior neuro-imaging. Questions regarding appropriateness of the most recent imaging, concordance of radiological interpretation, and re-evaluation of referring diagnoses were answered by the attending physician. Main Outcome Measures 1. The frequency and types of errors committed in the utilization of neuro-imaging. 2. The frequency of re-interpretation of pre-referral neuro-imaging studies following neuro-ophthalmic history and examination. Results Most study participants (84.5%; 71/84) underwent magnetic resonance imaging (MRI) prior to referral; 15.5% (13/84) underwent only computed tomography (CT). The rate of sub-optimal neuro-imaging studies was 38.1% (32/84). The three most common reasons for sub-optimal studies were incomplete area of imaging (34.4%; 11/32), wrong study type (28.1%; 9/32), and poor image quality (21.9%; 7/32). 24 of 84 subjects (28.6%) required additional neuro-imaging. We agreed with the radiology interpretation of the prior neuro-imaging studies in the majority (77.4%; 65/84) of patients. The most common anatomic locations for discordance in interpretation were the intraorbital optic nerve (35%; 7/20) and the brainstem (20%; 4

  4. Neuro-fuzzy Control of Integrating Processes

    Directory of Open Access Journals (Sweden)

    Anna Vasičkaninová

    2011-11-01

    Full Text Available Fuzzy technology is adaptive and easily applicable in different areas.Fuzzy logic provides powerful tools to capture the perceptionof natural phenomena. The paper deals with tuning of neuro-fuzzy controllers for integrating plant and for integrating plantswith time delay. The designed approach is verified on three examples by simulations and compared plants with classical PID control.Designed fuzzy controllers lead to better closed-loop control responses then classical PID controllers.

  5. MANIFESTATIONS NEURO-OPHTHALMOLOGIQUES DE LA ...

    African Journals Online (AJOL)

    L\\'oedème papillaire (17%) et les paralysies des nerfs oculo-moteurs (6%) touchant principalement le nerf oculo-moteur externe étaient les manifestations neuro-ophtalmologiques les plus fréquentes. L\\'amputation du champs visuel, la cécité corticale et le nystagmus étaient observés respectivement chez 5, 2 et 1 patient.

  6. Arquivos de Neuro-Psiquiatria: 75 years.

    Science.gov (United States)

    Teive, Hélio A Ghizoni; Caramelli, Paulo

    2018-01-01

    This year marks the 75th year of publication of Arquivos de Neuro-Psiquiatria (ANP), the official journal of the Brazilian Academy of Neurology and one of the most important neuroscience journals in Latin America. ANP was initially edited by Oswaldo Lange, its founder, and subsequently by Antonio Spina-França Netto and, in recent years, by José Antonio Livramento and Luís dos Ramos Machado.

  7. DNA replication stress: from molecular mechanisms to human disease.

    Science.gov (United States)

    Muñoz, Sergio; Méndez, Juan

    2017-02-01

    The genome of proliferating cells must be precisely duplicated in each cell division cycle. Chromosomal replication entails risks such as the possibility of introducing breaks and/or mutations in the genome. Hence, DNA replication requires the coordinated action of multiple proteins and regulatory factors, whose deregulation causes severe developmental diseases and predisposes to cancer. In recent years, the concept of "replicative stress" (RS) has attracted much attention as it impinges directly on genomic stability and offers a promising new avenue to design anticancer therapies. In this review, we summarize recent progress in three areas: (1) endogenous and exogenous factors that contribute to RS, (2) molecular mechanisms that mediate the cellular responses to RS, and (3) the large list of diseases that are directly or indirectly linked to RS.

  8. Molecular basis of human CD36 gene mutations.

    Science.gov (United States)

    Rać, Monika Ewa; Safranow, Krzysztof; Poncyljusz, Wojciech

    2007-01-01

    CD36 is a transmembrane glycoprotein of the class B scavenger receptor family. The CD36 gene is located on chromosome 7 q11.2 and is encoded by 15 exons. Defective CD36 is a likely candidate gene for impaired fatty acid metabolism, glucose intolerance, atherosclerosis, arterial hypertension, diabetes, cardiomyopathy, Alzheimer disease, and modification of the clinical course of malaria. Contradictory data concerning the effects of antiatherosclerotic drugs on CD36 expression indicate that further investigation of the role of CD36 in the development of atherosclerosis may be important for the prevention and treatment of this disease. This review summarizes current knowledge of CD36 gene structure, splicing, and mutations and the molecular, metabolic, and clinical consequences of these phenomena.

  9. Molecular basis of indomethacin-human serum albumin interaction

    DEFF Research Database (Denmark)

    Trivedi, V D; Vorum, H; Honoré, B

    1999-01-01

    Studies on the strength and extent of binding of the non-steroidal anti-inflammatory drug indomethacin to human serum albumin (HSA) have provided conflicting results. In the present work, the serum-binding of indomethacin was studied in 55 mM sodium phosphate buffer (pH 7.0) at 28 degrees C......, by using a fluorescence quench titration technique. The interaction of indomethacin with human serum albumin has been studied as a function of temperature, ionic strength and pH. The results suggest that electrostatic interaction plays a major role in the binding. The possible role of lysine residues...... in this interaction was studied by modifying exposed and buried lysine residues of HSA with potassium cyanate and studying indomethacin binding with the modified HSA. The data suggest that the interaction takes place via a salt bridge formation between the carboxylate group of indomethacin and a buried lysine residue...

  10. Molecular interactions of 'high risk' human papillomaviruses E6 and ...

    Indian Academy of Sciences (India)

    Unknown

    sequences in adenovirus E1A and human papillomavirus. E7 proteins mediate interaction with the same set of cellular proteins; J. Virol. 66 6893–6902. Eckner R, Ludlow J W, Lill N L, Oldread E, Arany Z, Modjta- hedi N, DeCaprio J A, Livingston D M and Morgan J A 1996. Association of p300 and CBP with simian virus 40 ...

  11. Glucocorticoids entrain molecular clock components in human peripheral cells.

    Science.gov (United States)

    Cuesta, Marc; Cermakian, Nicolas; Boivin, Diane B

    2015-04-01

    In humans, shift work induces a desynchronization between the circadian system and the outside world, which contributes to shift work-associated medical disorders. Using a simulated night shift experiment, we previously showed that 3 d of bright light at night fully synchronize the central clock to the inverted sleep schedule, whereas the peripheral clocks located in peripheral blood mononuclear cells (PBMCs) took longer to reset. This underlines the need for testing the effects of synchronizers on both the central and peripheral clocks. Glucocorticoids display circadian rhythms controlled by the central clock and are thought to act as synchronizers of rodent peripheral clocks. In the present study, we tested whether the human central and peripheral clocks were sensitive to exogenous glucocorticoids (Cortef) administered in the late afternoon. We showed that 20 mg Cortef taken orally acutely increased PER1 expression in PBMC peripheral clocks. After 6 d of Cortef administration, the phases of central markers were not affected, whereas those of PER2-3 and BMAL1 expression in PBMCs were shifted by ∼ 9.5-11.5 h. These results demonstrate, for the first time, that human peripheral clocks are entrained by glucocorticoids. Importantly, they suggest innovative interventions for shift workers and jet-lag travelers, combining synchronizing agents for the central and peripheral clocks. © FASEB.

  12. Molecular interactions between terpenoid mosquito repellents and human-secreted attractants.

    Science.gov (United States)

    Liao, Shengliang; Song, Jie; Wang, Zongde; Chen, Jinzhu; Fan, Guorong; Song, Zhanqian; Shang, Shibin; Chen, Shangxing; Wang, Peng

    2014-02-01

    Molecular interactions between terpenoid mosquito repellents and three typical human-secreted attractants, ammonia, 1-octen-3-ol, and formic acid were studied. Relative energies, bond distances, and bond angles of the molecular interactions were obtained at HF level to evaluate the interaction intensity and types. The effects of molecular interactions on repellency were investigated by the subsequent quantitative structure-activity relationship (QSAR) study. The results of this study suggest that attractant-repellent interaction should not be ignored and could be helpful for future research on the repelling mechanism of mosquito repellents. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Neuro-fuzzy system for prostate cancer diagnosis.

    Science.gov (United States)

    Benecchi, Luigi

    2006-08-01

    To develop a neuro-fuzzy system to predict the presence of prostate cancer. Neuro-fuzzy systems harness the power of two paradigms: fuzzy logic and artificial neural networks. We compared the predictive accuracy of our neuro-fuzzy system with that obtained by total prostate-specific antigen (tPSA) and percent free PSA (%fPSA). The data from 1030 men (both outpatients and hospitalized patients) were used. All men had a tPSA level of less than 20 ng/mL. Of the 1030 men, 195 (18.9%) had prostate cancer. A neuro-fuzzy system was developed using the coactive neuro-fuzzy inference system model. The mean area under the receiver operating characteristic curve for the neuro-fuzzy system output was 0.799 +/- 0.029 (95% confidence interval 0.760 to 0.835), for tPSA, it was 0.724 +/- 0.032 (95% confidence interval 0.681 to 0.765), and for %fPSA, 0.766 +/- 0.024 (95% confidence interval 0.725 to 0.804). Furthermore, pairwise comparison of the area under the curves evidenced differences among %fPSA, tPSA, and neuro-fuzzy system's output (tPSA versus neuro-fuzzy system's output, P = 0.008; %fPSA versus neuro-fuzzy system's output, P = 0.032). The comparison at 95% sensitivity showed that the neuro-fuzzy system had the best specificity (31.9%). This study presented a neuro-fuzzy system based on both serum data (tPSA and %fPSA) and clinical data (age) to enhance the performance of tPSA to discriminate prostate cancer. The predictive accuracy of the neuro-fuzzy system was superior to that of tPSA and %fPSA.

  14. Piracy on the molecular level: human herpesviruses manipulate cellular chemotaxis.

    Science.gov (United States)

    Cornaby, Caleb; Tanner, Anne; Stutz, Eric W; Poole, Brian D; Berges, Bradford K

    2016-03-01

    Cellular chemotaxis is important to tissue homeostasis and proper development. Human herpesvirus species influence cellular chemotaxis by regulating cellular chemokines and chemokine receptors. Herpesviruses also express various viral chemokines and chemokine receptors during infection. These changes to chemokine concentrations and receptor availability assist in the pathogenesis of herpesviruses and contribute to a variety of diseases and malignancies. By interfering with the positioning of host cells during herpesvirus infection, viral spread is assisted, latency can be established and the immune system is prevented from eradicating viral infection.

  15. Molecular interactions in human nail plate analysed by dielectric spectroscopy.

    Science.gov (United States)

    Marzec, E; Olszewski, J

    2009-02-15

    The influence of diabetes mellitus on dielectric properties of the human fingernail was measured in vitro in the alpha-dispersion region. The frequency dependencies of the permittivity and conductivity for the healthy and the diabetic nail plate revealed three separate relaxations, which were similar for both materials. Significant differences were observed in the values of permittivity at the same frequency between the healthy and the diabetic nails with low water content of about 0% and 3%. Results of this paper suggest that hyperglycemia alters the first-order structure of the nail keratin macromolecule.

  16. Molecular cytogenetic characterization of a human thyroid cancercell line

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Heinz-Ulrich G.; Tuton, Tiffany B.; Ito, Yuko; Chu, LisaW.; Lu, Chung-Mei; Baumgartner, Adolf; Zitzelsberger, Horst F.; Weier,Jingly F.

    2006-01-04

    The incidence of papillary thyroid carcinoma (PTC) increases significantly after exposure of the head and neck region to ionizing radiation, yet we know neither the steps involved in malignant transformation of thyroid epithelium nor the specific carcinogenic mode of action of radiation. Such increased tumor frequency became most evident in children after the 1986 nuclear accident in Chernobyl, Ukraine. In the twelve years following the accident, the average incidence of childhood PTCs (chPTC) increased over one hundred-fold compared to the rate of about 1 tumor incidence per 10{sup 6} children per year prior to 1986. To study the etiology of radiation-induced thyroid cancer, we formed an international consortium to investigate chromosomal changes and altered gene expression in cases of post-Chernobyl chPTC. Our approach is based on karyotyping of primary cultures established from chPTC specimens, establishment of cell lines and studies of genotype-phenotype relationships through high resolution chromosome analysis, DNA/cDNA micro-array studies, and mouse xenografts that test for tumorigenicity. Here, we report the application of fluorescence in situ hybridization (FISH)-based techniques for the molecular cytogenetic characterization of a highly tumorigenic chPTC cell line, S48TK, and its subclones. Using chromosome 9 rearrangements as an example, we describe a new approach termed ''BAC-FISH'' to rapidly delineate chromosomal breakpoints, an important step towards a better understanding of the formation of translocations and their functional consequences.

  17. A molecular dynamics study of human serum albumin binding sites.

    Science.gov (United States)

    Artali, Roberto; Bombieri, Gabriella; Calabi, Luisella; Del Pra, Antonio

    2005-01-01

    A 2.0 ns unrestrained Molecular Dynamics was used to elucidate the geometric and dynamic properties of the HSA binding sites. The structure is not stress affected and the rmsds calculated from the published crystallographic data are almost constant for all the simulation time, with an averaged value of 2.4A. The major variability is in the C-terminus region. The trajectory analysis of the IIA binding site put in evidence fast oscillations for the Cgamma@Leu203...Cgamma@Leu275 and Cgamma@Leu219...Cgamma@Leu260 distances, with fluctuations around 250 ps, 1000 ps and over for the first, while the second is smoothly increasing with the simulation time from 7 to 10A. These variations are consistent with a volume increase up to 20% confirmed by the inter-domain contacts analysis, in particular for the pair O@Pro148...Ogamma@Ser283, representing the change of distance between IB-h9 and IIA-h6, O@Glu149...Ogamma@Ser189 for sub-domains IB-h9/IIA-h1 and N@Val339...Odelta2@Asp447 sub-domains IIB-h9/IIIA-h1. These inter-domain motions confirm the flexibility of the unfatted HSA with possible binding site pre-formation.

  18. A neuro-fuzzy system for characterization of arm movements.

    Science.gov (United States)

    Balbinot, Alexandre; Favieiro, Gabriela

    2013-02-21

    The myoelectric signal reflects the electrical activity of skeletal muscles and contains information about the structure and function of the muscles which make different parts of the body move. Advances in engineering have extended electromyography beyond the traditional diagnostic applications to also include applications in diverse areas such as rehabilitation, movement analysis and myoelectric control of prosthesis. This paper aims to study and develop a system that uses myoelectric signals, acquired by surface electrodes, to characterize certain movements of the human arm. To recognize certain hand-arm segment movements, was developed an algorithm for pattern recognition technique based on neuro-fuzzy, representing the core of this research. This algorithm has as input the preprocessed myoelectric signal, to disclosed specific characteristics of the signal, and as output the performed movement. The average accuracy obtained was 86% to 7 distinct movements in tests of long duration (about three hours).

  19. A Neuro-Fuzzy System for Characterization of Arm Movements

    Directory of Open Access Journals (Sweden)

    Alexandre Balbinot

    2013-02-01

    Full Text Available The myoelectric signal reflects the electrical activity of skeletal muscles and contains information about the structure and function of the muscles which make different parts of the body move. Advances in engineering have extended electromyography beyond the traditional diagnostic applications to also include applications in diverse areas such as rehabilitation, movement analysis and myoelectric control of prosthesis. This paper aims to study and develop a system that uses myoelectric signals, acquired by surface electrodes, to characterize certain movements of the human arm. To recognize certain hand-arm segment movements, was developed an algorithm for pattern recognition technique based on neuro-fuzzy, representing the core of this research. This algorithm has as input the preprocessed myoelectric signal, to disclosed specific characteristics of the signal, and as output the performed movement. The average accuracy obtained was 86% to 7 distinct movements in tests of long duration (about three hours.

  20. Molecular mechanism of action of opioids in human neuroblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Yu, V.C.K.

    1987-01-01

    A series of human neuroblastoma cell lines was screened for the presence of opioid receptor sites. Of these cell lines, SK-N-SH was found to express approximately 50,000 ..mu.. and 10,000 delta opioid receptor sites/cell. In vitro characterization revealed that the binding properties of these receptor sites closely resembled those of human and rodent brain. Phosphatidylinositol turnover as a potential second messenger system for the ..mu.. receptor was examined in SK-N-SH cells. Neurotransmitter receptor systems were determined in the three sub-clones of SK-N-SH cells. Cells of the SH-SY5Y line, a phenotypically stable subclone of SK-N-SH cells, were induced to differentiate by treatment with various inducing agents, and changes of several neurotransmitter receptor systems were determined. Nerve growth factor (NGF) and retinoic acid (RA) up-regulated, while dBcAMP down-regulated opioid receptor sites. (/sup 3/H)Dopamine uptake was slightly enhanced only in RA-treated cells. Strikingly, the efficacy of PGE/sub 1/-stimulated accumulation of cAMP was enhanced by 15- to 30-fold upon RA treatment.

  1. Molecular epidemiology of human rabies viruses in Sri Lanka.

    Science.gov (United States)

    Matsumoto, Takashi; Ahmed, Kamruddin; Karunanayake, Dushantha; Wimalaratne, Omala; Nanayakkara, Susilakanthi; Perera, Devika; Kobayashi, Yuji; Nishizono, Akira

    2013-08-01

    Rabies is a lethal zoonotic disease caused by the rabies virus, which is transmitted by rabid animals to humans. Rabies is prevalent in all continents, with over 60% of human deaths occurring in Asia. Sri Lanka is a rabies-endemic country. This study shows that rabies afflicted more older individuals than children in Sri Lanka between 2008 and 2010. This novel finding indicates that older people in Sri Lanka should be more aware of the risk of rabies. Phylogenetic analyses of the rabies N and G genes showed that the Sri Lankan rabies viruses are distinct and probably originated from a single clone. The G-L noncoding region is highly diverse, and is suitable for the analysis of virus evolution within a country. A phylogenetic analysis of this region showed high diversity in the currently circulating Sri Lankan rabies viruses, which can be divided into seven clades. Some clades are unique to a specific geographic region, whereas others occur at multiple locations. This indicates that the movement of dogs, the main rabies-transmitting animal in Sri Lanka, is restricted in some areas but less limited in others. These data may help to formulate a more efficient rabies control program in Sri Lanka. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Molecular characterization of a cloned human oxytocin receptor.

    Science.gov (United States)

    Kimura, T; Makino, Y; Saji, F; Takemura, M; Inoue, T; Kikuchi, T; Kubota, Y; Azuma, C; Nobunaga, T; Tokugawa, Y

    1994-10-01

    We describe here the binding and functional properties of a cloned human oxytocin receptor (OTR). We established a transient OTR expression system on COS-1 cells, which do not express vasopressin receptors. With the transfected cells and [3H]oxytocin, the dissociation constant (Kd) of OTR to oxytocin was 6.0 +/- 1.1 nmol/l; the binding properties of several oxytocin-related peptides were also examined. The functional properties of OTR were determined by an electrophysiological method, using a Xenopus laevis oocyte injected with in vitro transcribed OTR mRNA. These two methods showed that [Phe2,Orn8]vasotocin, a vasopressin agonist, was an OTR antagonist. A combination of these methods using cloned OTR cDNA is a novel and effective method for the investigation of oxytocin-related ligands.

  3. Ligand induced conformational changes of the human serotonin transporter revealed by molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Heidi Koldsø

    Full Text Available The competitive inhibitor cocaine and the non-competitive inhibitor ibogaine induce different conformational states of the human serotonin transporter. It has been shown from accessibility experiments that cocaine mainly induces an outward-facing conformation, while the non-competitive inhibitor ibogaine, and its active metabolite noribogaine, have been proposed to induce an inward-facing conformation of the human serotonin transporter similar to what has been observed for the endogenous substrate, serotonin. The ligand induced conformational changes within the human serotonin transporter caused by these three different types of ligands, substrate, non-competitive and competitive inhibitors, are studied from multiple atomistic molecular dynamics simulations initiated from a homology model of the human serotonin transporter. The results reveal that diverse conformations of the human serotonin transporter are captured from the molecular dynamics simulations depending on the type of the ligand bound. The inward-facing conformation of the human serotonin transporter is reached with noribogaine bound, and this state resembles a previously identified inward-facing conformation of the human serotonin transporter obtained from molecular dynamics simulation with bound substrate, but also a recently published inward-facing conformation of a bacterial homolog, the leucine transporter from Aquifex Aoelicus. The differences observed in ligand induced behavior are found to originate from different interaction patterns between the ligands and the protein. Such atomic-level understanding of how an inhibitor can dictate the conformational response of a transporter by ligand binding may be of great importance for future drug design.

  4. Binding of ibuprofen to human hemoglobin: elucidation of their molecular recognition by spectroscopy, calorimetry, and molecular modeling techniques.

    Science.gov (United States)

    Seal, Paromita; Sikdar, Jyotirmoy; Roy, Amartya; Haldar, Rajen

    2017-10-11

    Ibuprofen, used for the treatment of acute and chronic pain, osteoarthritis, rheumatoid arthritis, and related conditions has ample affinity to globular proteins. Here we have explored this fundamental study pertaining to the interaction of ibuprofen with human hemoglobin (HHb), using multispectroscopic, calorimetric, and molecular modeling techniques to gain insights into molecular aspects of binding mechanism. Ibuprofen-induced graded decrease in absorption spectra indicates protein disruption along with sedimentation of HHb particle. Red shifting of absorption peak at 195 nm indicates alteration in the secondary structure of HHb upon interaction with ibuprofen. Flouremetric and isothermal titration calorimetric (ITC) studies suggested one binding site in HHb for ibuprofen at 298.15 K. However, with increase in temperature, ITC revealed increasing number of binding sites. The negative values of Gibbs energy change (ΔG0) and enthalpy change (ΔH0) along with positive value of entropy change (ΔS0) strongly suggest that it is entropy-driven spontaneous exothermic reaction. Moreover, hydrophobic interaction, hydrogen bonding, and π-π interaction play major role in this binding process as evidenced from ANS (8-anilino-1-napthalenesulphonic acid), sucrose binding, and molecular modeling studies. The interaction impacts on structural integrity and functional aspects of HHb as confirmed by CD spectroscopy, increased free iron release, increased rate of co-oxidation and decreased rate of esterase activity. These findings suggest us to conclude that ibuprofen upon interaction perturbs both structural and functional aspects of HHb.

  5. Can chromatin conformation technologies bring light into human molecular pathology?

    Science.gov (United States)

    Kubiak, Marta; Lewandowska, Marzena Anna

    2015-01-01

    Regulation of gene expression in eukaryotes involves many complex processes, in which chromatin structure plays an important role. In addition to the epigenetic effects, such as DNA methylation and phosphorylation or histone modifications, gene expression is also controlled by the spatial organization of chromatin. For example, distant regulatory elements (enhancers, insulators) may come into direct physical interaction with target genes or other regulatory elements located in genomic regions of up to several hundred kilobases in size. Such long-range interactions result in the formation of chromatin loops. In the last several years, there has been a rapid increase in our knowledge of the spatial organization of chromatin in the nucleus through the chromosome conformation capture (3C) technology. Here we review and compare the original 3C and 3C-based methods including chromosome conformation capture-on-chip (4C), chromosome conformation capture carbon copy (5C), hi-resolution chromosome confomation capture (HiC). In this article, we discuss different aspects of how the nuclear organization of chromatin is associated with gene expression regulation and how this knowledge is useful in translational medicine and clinical applications. We demonstrate that the knowledge of the chromatin 3D organization may help understand the mechanisms of gene expression regulation of genes involved in the development of human diseases, such as CFTR (responsible for cystic fibrosis) or IGFBP3 (associated with breast cancer pathogenesis). Additionally, 3C-derivative methods have been also useful in the diagnosis of some leukemia subtypes.

  6. Molecular studies of deletions at the human steroid sulfatase locus

    Energy Technology Data Exchange (ETDEWEB)

    Shapiro, L.J.; Yen, P.; Pomerantz, D.; Martin, E.; Rolewic, L.; Mohandas, T. (Univ. of California, Los Angeles (USA))

    1989-11-01

    The human steroid sulfatase gene (STS) is located on the distal X chromosome short arm close to the pseudoautosomal region but in a segment of DNA that is unique to the X chromosome. In contrast to most X chromosome-encoded genes, STS expression is not extinguished during the process of X chromosome inactivation. Deficiency of STS activity produced the syndrome of X chromosome-linked ichthyosis, which is one of the most common inborn errors of metabolism in man. Approximately 90% of STS{sup {minus}} individuals have large deletions at the STS locus. The authors and others have found that the end points of such deletions are heterogeneous in their location. One recently ascertained subject was observed to have a 40-kilobase deletion that is entirely intragenic, permitting the cloning and sequencing of the deletion junction. Studies of this patient and of other X chromosome sequences in other subjects permit some insight into the mechanism(s) responsible for generating frequent deletions on the short arm of the X chromosome.

  7. Molecular evidence for human alpha 2-HS glycoprotein (AHSG) polymorphism.

    Science.gov (United States)

    Osawa, M; Umetsu, K; Ohki, T; Nagasawa, T; Suzuki, T; Takeichi, S

    1997-01-01

    Alpha 2-HS glycoprotein (AHSG) is a human plasma glycoprotein that exhibits genetic polymorphism on isoelectric focusing (IEF). To identify the origin of two common alleles, AHSG*1 and *2, we examined nucleotide exchanges in the gene. AHSG cDNA was obtained by RT-PCR from poly(A) RNA of seven liver tissue samples and subcloned into a plasmid vector. After sequencing, we found six single nucleotide differences in comparison with the originally reported sequence. In particular, the nucleotide substitutions of C to T at amino acid position 230 and C to G at position 238 were common among the samples exhibiting phenotype 2-1 or 2. Since these substitutions might give rise to a NlaIII site and a SacI site, respectively, for the potential AHSG*2, we analyzed these substitutions by PCR-RFLP using genomic DNA of 68 individuals. The result was consistent with the IEF analysis of the corresponding serum, indicating that AHSG*1 was characterized by ACG (Thr) at position 230 in exon 6 and ACC (Thr) at position 238 in exon 7, and that AHSG*2 was characterized by ATG (Met) at position 230 and AGC (Ser) at position 238.

  8. Functional and molecular outcomes of the human masticatory muscles.

    Science.gov (United States)

    Isola, G; Anastasi, G P; Matarese, G; Williams, R C; Cutroneo, G; Bracco, P; Piancino, M G

    2017-11-20

    The masticatory muscles achieve a broad range of different activities such as chewing, sucking, swallowing, and speech. In order to accomplish these duties, masticatory muscles have a unique and heterogeneous structure and fiber composition, enabling them to produce their strength and contraction speed largely dependent on their motor units and myosin proteins that can change in response to genetic and environmental factors. Human masticatory muscles express unique myosin isoforms, including a combination of thick fibers, expressing myosin light chains (MyLC) and myosin class I and II heavy chains (MyHC) -IIA, -IIX, α-cardiac, embryonic and neonatal and thin fibers, respectively. In this review, we discuss the current knowledge regarding the importance of fiber-type diversity in masticatory muscles versus supra- and infrahyoid muscles, and versus limb and trunk muscles. We also highlight new information regarding the adaptive response and specific genetic variations of muscle fibers on the functional significance of the masticatory muscles, which influences craniofacial characteristics, malocclusions, or asymmetry. These findings may offer future possibilities for the prevention of craniofacial growth disturbances. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  9. Interactive Domains in the Molecular Chaperone Human ?B Crystallin Modulate Microtubule Assembly and Disassembly

    OpenAIRE

    Ghosh, Joy G.; Houck, Scott A.; Clark, John I.

    2007-01-01

    Small heat shock proteins regulate microtubule assembly during cell proliferation and in response to stress through interactions that are poorly understood.Novel functions for five interactive sequences in the small heat shock protein and molecular chaperone, human alphaB crystallin, were investigated in the assembly/disassembly of microtubules and aggregation of tubulin using synthetic peptides and mutants of human alphaB crystallin.The interactive sequence (113)FISREFHR(120) exposed on the ...

  10. Modeling human risk: Cell & molecular biology in context

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-06-01

    It is anticipated that early in the next century manned missions into outer space will occur, with a mission to Mars scheduled between 2015 and 2020. However, before such missions can be undertaken, a realistic estimation of the potential risks to the flight crews is required. One of the uncertainties remaining in this risk estimation is that posed by the effects of exposure to the radiation environment of outer space. Although the composition of this environment is fairly well understood, the biological effects arising from exposure to it are not. The reasons for this are three-fold: (1) A small but highly significant component of the radiation spectrum in outer space consists of highly charged, high energy (HZE) particles which are not routinely experienced on earth, and for which there are insufficient data on biological effects; (2) Most studies on the biological effects of radiation to date have been high-dose, high dose-rate, whereas in space, with the exception of solar particle events, radiation exposures will be low-dose, low dose-rate; (3) Although it has been established that the virtual absence of gravity in space has a profound effect on human physiology, it is not clear whether these effects will act synergistically with those of radiation exposure. A select panel will evaluate the utilizing experiments and models to accurately predict the risks associated with exposure to HZE particles. Topics of research include cellular and tissue response, health effects associated with radiation damage, model animal systems, and critical markers of Radiation response.

  11. Neuro-epistemology: a post-modernist analysis of the neuro ...

    African Journals Online (AJOL)

    This paper examines the theoretical framework in which we construct our terms of reference when examining patients from an integrated Meyerian biopsychosocial perspective. We coin the term iยDneuro-epistemologylo, defining the frame for scientific inquiry into the nature and status of knowledge in neuro-sciences, ...

  12. [To strengthen the education on basic knowledge and skills of neuro-ophthalmology].

    Science.gov (United States)

    Zhang, Xiao-jun; Wang, Ning-li

    2011-12-01

    Basic knowledge and skills are cornerstone of the diagnosis and treatment of neuro-ophthalmology diseases in ophthalmology practice. Due to the interdisciplinary features of neuro-ophthalmology, neuro-anatomy, neuro-physiology related to eyes, neuro-image and neuro-electrodiagnosis, these should be included in the education for the ophthalmologist. Special attention should be paid to training on capability of logically thinking in neuro-ophthalmology. Multiple ways can be used for the education of ophthalmologists and neurologists for the enhancement of basic knowledge and skills of neuro-ophthalmology in China.

  13. The Danish Neuro-Oncology Registry

    Directory of Open Access Journals (Sweden)

    Hansen S

    2016-10-01

    Full Text Available Steinbjørn Hansen Department of Oncology, Odense University Hospital and Institute of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark Aim of database: The Danish Neuro-Oncology Registry (DNOR was established by the Danish Neuro-Oncology Group as a national clinical database. It was established for the purpose of supporting research and development in adult patients with primary brain tumors in Denmark. Study population: DNOR has registered clinical data on diagnostics and treatment of all adult patients diagnosed with glioma since January 1, 2009, which numbers approximately 400 patients each year. Main variables: The database contains information about symptoms, presurgical magnetic resonance imaging (MRI characteristics, performance status, surgical procedures, residual tumor on postsurgical MRI, postsurgical complications, diagnostic and histology codes, radiotherapy, and chemotherapy. Descriptive data: DNOR publishes annual reports on descriptive data. During the period of registration, postoperative MRI is performed in a higher proportion of the patients (Indicator II, and a higher proportion of patients have no residual tumor after surgical resection of the primary tumor (Indicator IV. Further data are available in the annual reports. The indicators reflect only minor elements of handling brain tumor patients. Another advantage of reporting indicators is the related multidisciplinary discussions giving a better understanding of what actually is going on, thereby facilitating the work on adjusting the national guidelines in the Danish Neuro-Oncology Group. Conclusion: The establishment of DNOR has optimized the quality in handling primary brain tumor patients in Denmark by reporting indicators and facilitating a better multidisciplinary collaboration at a national level. DNOR provides a valuable resource for research. Keywords: brain neoplasms, brain cancer, glioma, clinical quality indicators

  14. Molecular identification and characterisation of bifidobacteria and lactobacilli in the human gastrointestinal tract

    NARCIS (Netherlands)

    Satokari, R.

    2002-01-01

    Bifidobacteria and lactobacilli are considered to be members of the beneficial microbiota in the human gastrointestinal (GI) tract. The present study describes the development and validation of new molecular methods for the detection and analysis of bifidobacteria and lactobacilli and the

  15. Molecular biological methods for studying the gut microbiota : the EU human gut flora project

    NARCIS (Netherlands)

    Blaut, M; Collins, MD; Welling, GW; Dore, J; van Loo, J; de Vos, W

    Seven European laboratories co-operated in a joint project (FAIR CT97-3035) to develop, refine and apply molecular methods towards facilitating elucidation of the complex composition of the human intestinal microflora and to devise robust methodologies for monitoring the gut flora in response to

  16. More on contamination: the use of asymmetric molecular behavior to identify authentic ancient human DNA

    DEFF Research Database (Denmark)

    Malmström, Helena; Svensson, Emma M; Gilbert, M Thomas P

    2007-01-01

    the reliability of one of the proposed criteria, that of appropriate molecular behavior. Using real-time polymerase chain reaction (PCR) and pyrosequencing, we have quantified the relative levels of authentic aDNA and contaminant human DNA sequences recovered from archaeological dog and cattle remains. In doing...

  17. Clinical and molecular characterisation of human syndromes with congenital patellar malformations

    NARCIS (Netherlands)

    Bongers, M.H.F.

    2006-01-01

    In this thesis the results are described of clinical and molecular investigation of human syndromes with congenital patellar malformations as a hallmark feature, with emphasis on nail patella syndrome, small patella syndrome, isolated patellar aplasia or hypoplasia, and Meier-Gorlin syndrome. The

  18. MOLECULAR ANALYSIS OF HUMAN SPERMATOZOA: POTENTIAL FOR INFERTILITY RESEARCH AND SCREENING

    Science.gov (United States)

    Molecular Analysis of Human Spermatozoa: Potential for Infertility Research and ScreeningDavid Miller1, David Dix2, Robert Reid3, Susan Wykes3 and Stephen Krawetz3 1Reproductive Biology Group, University of Leeds, UK2Reproductive Toxicology Division, U.S. Environmenta...

  19. Molecular biological methods for studying the gut microbiota : the EU human gut flora project

    NARCIS (Netherlands)

    Blaut, M.; Collins, M.D.; Welling, G.W.; Dore, J.; Loo, van J.; Vos, de W.M.

    2002-01-01

    Seven European laboratories co-operated in a joint project (FAIR CT97-3035) to develop, refine and apply molecular methods towards facilitating elucidation of the complex composition of the human intestinal microflora and to devise robust methodologies for monitoring the gut flora in response to

  20. Molecular epidemiology and evolution of human respiratory syncytial virus and human metapneumovirus

    NARCIS (Netherlands)

    Gaunt, Eleanor R.; Jansen, Rogier R.; Poovorawan, Yong; Templeton, Kate E.; Toms, Geoffrey L.; Simmonds, Peter

    2011-01-01

    Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are ubiquitous respiratory pathogens of the Pneumovirinae subfamily of the Paramyxoviridae. Two major surface antigens are expressed by both viruses; the highly conserved fusion (F) protein, and the extremely diverse

  1. Molecular Epidemiology and Evolution of Human Respiratory Syncytial Virus and Human Metapneumovirus

    NARCIS (Netherlands)

    Gaunt, E.R.; Jansen, R.R.; Poovorawan, Y.; Templeton, K.E.; Toms, G.L.; Simmonds, P.

    2011-01-01

    Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are ubiquitous respiratory pathogens of the Pneumovirinae subfamily of the Paramyxoviridae. Two major surface antigens are expressed by both viruses; the highly conserved fusion (F) protein, and the extremely diverse

  2. THE PROGRAMMING NEURO-LINGUISTICS AND THEIR APPLICABILITY IN THE PROCESS OF RECRUITMENT AND SELECTION

    OpenAIRE

    Gilma Álamo Sánchez; Yuhane Sangronis

    2008-01-01

    He/she is carried out a study referred to tools of Programming Neuro-linguistics (PNL) for the Selection, Employment and Training that allow choosing the appropriate personnel taking the language and the behavior as a result. For their development theories were revised referred to the PNL and the recruitment process and selection sustained in the process of the interview. The summations are oriented to the importance and convenience for the Management of Human resources of applying the Progra...

  3. Neuro-Inspired Computing with Stochastic Electronics

    KAUST Repository

    Naous, Rawan

    2016-01-06

    The extensive scaling and integration within electronic systems have set the standards for what is addressed to as stochastic electronics. The individual components are increasingly diverting away from their reliable behavior and producing un-deterministic outputs. This stochastic operation highly mimics the biological medium within the brain. Hence, building on the inherent variability, particularly within novel non-volatile memory technologies, paves the way for unconventional neuromorphic designs. Neuro-inspired networks with brain-like structures of neurons and synapses allow for computations and levels of learning for diverse recognition tasks and applications.

  4. Advanced MR Imaging in Neuro-oncology.

    Science.gov (United States)

    Radbruch, A; Bendszus, M

    2015-10-01

    The value of magnetic resonance (MR) imaging for the clinical management of brain tumour patients has greatly increased in recent years through the introduction of functional MR sequences. Previously, MR imaging for brain tumours relied for the most part on contrast-enhanced T1-weighted MR sequences but today with the help of advanced functional MR sequences, the pathophysiological aspects of tumour growth can be directly visualised and investigated. This article will present the pathophysiological background of the MR sequences relevant to neuro-oncological imaging as well as potential clinical applications. Ultimately, we take a look at possible future developments for ultra-high-field MR imaging.

  5. Expert system to predict effects of noise pollution on operators of power plant using neuro-fuzzy approach.

    Science.gov (United States)

    Ahmed, Hameed Kaleel; Zulquernain, Mallick

    2009-01-01

    Ration power plants, to generate power, have become common worldwide. One such one is the steam power plant. In such plants, various moving parts of heavy machines generate a lot of noise. Operators are subjected to high levels of noise. High noise level exposure leads to psychological as well physiological problems; different kinds of ill effects. It results in deteriorated work efficiency, although the exact nature of work performance is still unknown. To predict work efficiency deterioration, neuro-fuzzy tools are being used in research. It has been established that a neuro-fuzzy computing system helps in identification and analysis of fuzzy models. The last decade has seen substantial growth in development of various neuro-fuzzy systems. Among them, adaptive neuro-fuzzy inference system provides a systematic and directed approach for model building and gives the best possible design parameters in minimum possible time. This study aims to develop a neuro-fuzzy model to predict the effects of noise pollution on human work efficiency as a function of noise level, exposure time, and age of the operators doing complex type of task.

  6. Performance evaluation of neuro-PET using silicon photomultipliers

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Jiwoong; Choi, Yong, E-mail: ychoi@sogang.ac.kr; Jung, Jin Ho, E-mail: jinho1115@gmail.com; Kim, Sangsu; Im, Ki Chun

    2016-05-21

    Recently, we have developed the second prototype Silicon photomultiplier (SiPM) based positron emission tomography (PET) scanner for human brain imaging. The PET system was comprised of detector block which consisted of 4×4 SiPMs and 4×4 Lutetium Yttrium Orthosilicate arrays, charge signal transmission method, high density position decoder circuit and FPGA-embedded ADC boards. The purpose of this study was to evaluate the performance of the newly developed neuro-PET system. The energy resolution, timing resolution, spatial resolution, sensitivity, stability of the photo-peak position and count rate performance were measured. Tomographic image of 3D Hoffman brain phantom was also acquired to evaluate imaging capability of the neuro-PET. The average energy and timing resolutions measured for 511 keV gamma rays were 17±0.1% and 3±0.3 ns, respectively. Spatial resolution and sensitivity at the center of field of view (FOV) were 3.1 mm and 0.8%, respectively. The average scatter fraction was 0.4 with an energy window of 350–650 keV. The maximum true count rate and maximum NECR were measured as 43.3 kcps and 6.5 kcps at an activity concentration of 16.7 kBq/ml and 5.5 kBq/ml, respectively. Long-term stability results show that there was no significant change in the photo-peak position, energy resolution and count rate for 60 days. Phantom imaging studies were performed and they demonstrated the feasibility for high quality brain imaging. The performance tests and imaging results indicate that the newly developed PET is useful for brain imaging studies, if the axial FOV is extended to improve the system sensitivity.

  7. Roles of neuro-exocytotic proteins at the neuromuscular junction

    NARCIS (Netherlands)

    Sons-Michel, Michèle S.

    2011-01-01

    The aim of the studies described in the thesis was to elucidate the roles of several neuro-exocytotic proteins at the motor nerve terminal in neuromuscular synaptic transmission, making use of genetic knockout (KO) mice, each missing one (or more) neuro-exocytotic proteins. In addition, it was

  8. Neuro-flow Dynamics and the Learning Processes

    OpenAIRE

    Tatsuno, M.; Aizawa, Y.

    1997-01-01

    A new description of the neural activity is introduced by the neuro-flow dynamics and the extended Hebb rule. The remarkable characteristics of the neuro-flow dynamics, such as the primacy and the recency effect during awakeness or sleep, are pointed out.

  9. Improving English Instruction through Neuro-Linguistic Programming

    Science.gov (United States)

    Helm, David Jay

    2009-01-01

    This study examines the background information and numerous applications of neuro-linguistic programming as it applies to improving English instruction. In addition, the N.L.P. modalities of eye movement, the use of predicates, and posturing are discussed. Neuro-linguistic programming presents all students of English an opportunity to reach their…

  10. A Review of Neuro-ophthalmologic Emergencies | Fiebai | Nigerian ...

    African Journals Online (AJOL)

    Method: The available literature on neuro-ophthalmologic emergencies was reviewed, using available journals and internet based search engines and resources. Keywords employed were Neuro-ophthalmology Emergency and Ocular Morbidity. Result: The incidence of this group of emergencies is lower than that of other ...

  11. A Comprehensive Experiment for Molecular Biology: Determination of Single Nucleotide Polymorphism in Human REV3 Gene Using PCR-RFLP

    Science.gov (United States)

    Zhang, Xu; Shao, Meng; Gao, Lu; Zhao, Yuanyuan; Sun, Zixuan; Zhou, Liping; Yan, Yongmin; Shao, Qixiang; Xu, Wenrong; Qian, Hui

    2017-01-01

    Laboratory exercise is helpful for medical students to understand the basic principles of molecular biology and to learn about the practical applications of molecular biology. We have designed a lab course on molecular biology about the determination of single nucleotide polymorphism (SNP) in human REV3 gene, the product of which is a subunit of…

  12. Molecular docking analysis of curcumin analogues as human neutrophil elastase inhibitors

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Narayanaswamy

    2014-03-01

    Full Text Available In the present study, we aimed to dock 17 different ligands of curcumin analogues with that of human neutrophil elastase. Molecular descriptors analysis using Molinspiration online tool was carried out including investigation on human neutrophil elastase putative binding sites using Discovery Studio. The molecular physicochemical analysis revealed that all of the curcumin analogues complied well with the five rules of thumb. With regard to bioact-ivity score, compound 17 has exhibited least score towards nuclear receptor ligand (0.05 and enzyme inhibitor (0.10 compared to all other ligands. Compounds 2, 4 and 13 exhibited the maximum interaction energy (-40 kcal/mol. Interestingly, seven compounds namely 3, 11-14, 16 and 17 interacted well with Arg147 amino acid residue. The present study outcomes therefore might provide new insight in understanding these 17 curcumin analogues as potential candidates for human neutrophil elastase inhibitory agents.

  13. Accelerating Translational Research through Open Science: The Neuro Experiment.

    Science.gov (United States)

    Gold, E Richard

    2016-12-01

    Translational research is often afflicted by a fundamental problem: a limited understanding of disease mechanisms prevents effective targeting of new treatments. Seeking to accelerate research advances and reimagine its role in the community, the Montreal Neurological Institute (Neuro) announced in the spring of 2016 that it is launching a five-year experiment during which it will adopt Open Science-open data, open materials, and no patenting-across the institution. The experiment seeks to examine two hypotheses. The first is whether the Neuro's Open Science initiative will attract new private partners. The second hypothesis is that the Neuro's institution-based approach will draw companies to the Montreal region, where the Neuro is based, leading to the creation of a local knowledge hub. This article explores why these hypotheses are likely to be true and describes the Neuro's approach to exploring them.

  14. Understanding the molecular mechanisms of human microtia via a pig model of HOXA1 syndrome

    Directory of Open Access Journals (Sweden)

    Ruimin Qiao

    2015-06-01

    Full Text Available Microtia is a congenital malformation of the outer ears. Although both genetic and environmental components have been implicated in microtia, the genetic causes of this innate disorder are poorly understood. Pigs have naturally occurring diseases comparable to those in humans, providing exceptional opportunity to dissect the molecular mechanism of human inherited diseases. Here we first demonstrated that a truncating mutation in HOXA1 causes a monogenic disorder of microtia in pigs. We further performed RNA sequencing (RNA-Seq analysis on affected and healthy pig embryos (day 14.25. We identified a list of 337 differentially expressed genes (DEGs between the normal and mutant samples, shedding light on the transcriptional network involving HOXA1. The DEGs are enriched in biological processes related to cardiovascular system and embryonic development, and neurological, renal and urological diseases. Aberrant expressions of many DEGs have been implicated in human innate deformities corresponding to microtia-associated syndromes. After applying three prioritizing algorithms, we highlighted appealing candidate genes for human microtia from the 337 DEGs. We searched for coding variants of functional significance within six candidate genes in 147 microtia-affected individuals. Of note, we identified one EVC2 non-synonymous mutation (p.Asp1174Asn as a potential disease-implicating variant for a human microtia-associated syndrome. The findings advance our understanding of the molecular mechanisms underlying human microtia, and provide an interesting example of the characterization of human disease-predisposing variants using pig models.

  15. Human tumor-associated viruses and new insights into the molecular mechanisms of cancer.

    Science.gov (United States)

    Martin, D; Gutkind, J S

    2008-12-01

    The study of acute-transforming retroviruses and their oncogenes and of the multiple mechanisms deployed by DNA viruses to circumvent the growth-suppressive and proapoptotic function of tumor suppressor genes has provided the foundation of our current understanding of cancer biology. Unlike acute-transforming animal viruses, however, human tumor-associated viruses lead to malignancies with a prolonged latency and in conjunction with other environmental and host-related cooperating events. The relevance of viral infection to human cancer development has often been debated. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus (HPV), human T-cell lymphotropic virus (HTLV-1) and Kaposi's associated sarcoma virus (KSHV) contribute to 10-15% of the cancers worldwide. Hence, the opportunity exists to fight cancer at the global scale by preventing the spread of these viruses, by the development and distribution of effective and safe antiviral vaccines, and by identifying their oncogenic mechanism. Here, we discuss the molecular events underlying the neoplastic potential of the human tumor-associated viruses, with emphasis on the enigmatic KSHV and its numerous virally hijacked proangiogenic, immune-evasive and tumor-promoting genes. The emerging information may facilitate the development of new molecular-targeted approaches to prevent and treat virally associated human malignancies.

  16. Neuro-pharmacological functional MRI of epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Kiriyama, Hideki; Makabe, Tetsuo; Tomita, Susumu; Omoto, Takashi; Asari, Shoji [Okayama Univ. (Japan). School of Medicine; Aihara, Hiroshi; Kinugasa, Kazushi; Nishimoto, Akira; Ito, Takahiko

    2000-03-01

    We studied patients with epilepsy by neuro-pharmacological functional MRI technique using diazepam. Five normal volunteers and 7 patients with epilepsy were investigated. MRI was performed by a 1.5 T unit (SIGNA Horizon, GE) using the following parameters: TR/TE 5000 msec/80 msec, FA 90 deg, FOV 200 mm, matrix 128 x 128, slice thickness 7 mm. We performed MRI scanning over 5 minutes (2 minutes before and 3 minutes after injection of diazepam) for each 1 session; we scanned 3 sessions for each patient at intervals of 5 minutes. The diazepam was injected rapidly from the antecubital vein. The dose of diazepam was 0.05 mg/kg/injection (total dose was 0.15 mg/kg). The data were analyzed statistically using t-test. Signal change after administration of diazepam was less than 1 to 2% in healthy volunteers. By contrast, in patient with epilepsy, the signal change was almost 3%, which was significantly greater than that of the normal area (p=0.01). The neuro-pharmacological functional MRI technique using diazepam might be a useful method to identify epileptic foci. (author)

  17. Updates from the 2013 Society for Neuro-Oncology annual and World Federation for Neuro-Oncology quadrennial meeting.

    Science.gov (United States)

    Lukas, Rimas V; Amidei, Christina

    2014-01-01

    We present an overview of a number of key clinical studies in infiltrating gliomas presented at the 2013 Society for Neuro-Oncology and World Federation of Neuro-Oncology joint meeting. This review focuses on efficacy results, including quality of life studies, from larger clinical trials in both high- and low-grade infiltrating gliomas.

  18. HLA DNA sequence variation among human populations: molecular signatures of demographic and selective events.

    Directory of Open Access Journals (Sweden)

    Stéphane Buhler

    Full Text Available Molecular differences between HLA alleles vary up to 57 nucleotides within the peptide binding coding region of human Major Histocompatibility Complex (MHC genes, but it is still unclear whether this variation results from a stochastic process or from selective constraints related to functional differences among HLA molecules. Although HLA alleles are generally treated as equidistant molecular units in population genetic studies, DNA sequence diversity among populations is also crucial to interpret the observed HLA polymorphism. In this study, we used a large dataset of 2,062 DNA sequences defined for the different HLA alleles to analyze nucleotide diversity of seven HLA genes in 23,500 individuals of about 200 populations spread worldwide. We first analyzed the HLA molecular structure and diversity of these populations in relation to geographic variation and we further investigated possible departures from selective neutrality through Tajima's tests and mismatch distributions. All results were compared to those obtained by classical approaches applied to HLA allele frequencies.Our study shows that the global patterns of HLA nucleotide diversity among populations are significantly correlated to geography, although in some specific cases the molecular information reveals unexpected genetic relationships. At all loci except HLA-DPB1, populations have accumulated a high proportion of very divergent alleles, suggesting an advantage of heterozygotes expressing molecularly distant HLA molecules (asymmetric overdominant selection model. However, both different intensities of selection and unequal levels of gene conversion may explain the heterogeneous mismatch distributions observed among the loci. Also, distinctive patterns of sequence divergence observed at the HLA-DPB1 locus suggest current neutrality but old selective pressures on this gene. We conclude that HLA DNA sequences advantageously complement HLA allele frequencies as a source of data used

  19. Diurnal and seasonal molecular rhythms in human neocortex and their relation to Alzheimer's disease.

    Science.gov (United States)

    Lim, Andrew S P; Klein, Hans-Ulrich; Yu, Lei; Chibnik, Lori B; Ali, Sanam; Xu, Jishu; Bennett, David A; De Jager, Philip L

    2017-04-03

    Circadian and seasonal rhythms are seen in many species, modulate several aspects of human physiology, including brain functions such as mood and cognition, and influence many neurological and psychiatric illnesses. However, there are few data regarding the genome-scale molecular correlates underlying these rhythms, especially in the human brain. Here, we report widespread, site-specific and interrelated diurnal and seasonal rhythms of gene expression in the human brain, and show their relationship with parallel rhythms of epigenetic modification including histone acetylation, and DNA methylation. We also identify transcription factor-binding sites that may drive these effects. Further, we demonstrate that Alzheimer's disease pathology disrupts these rhythms. These data suggest that interrelated diurnal and seasonal epigenetic and transcriptional rhythms may be an important feature of human brain biology, and perhaps human biology more broadly, and that changes in such rhythms may be consequences of, or contributors to, diseases such as Alzheimer's disease.

  20. Capturing the diversity of the human gut microbiota through culture-enriched molecular profiling.

    Science.gov (United States)

    Lau, Jennifer T; Whelan, Fiona J; Herath, Isiri; Lee, Christine H; Collins, Stephen M; Bercik, Premysl; Surette, Michael G

    2016-07-01

    The human gut microbiota has been implicated in most aspects of health and disease; however, most of the bacteria in this community are considered unculturable, so studies have relied on molecular-based methods. These methods generally do not permit the isolation of organisms, which is required to fully explore the functional roles of bacteria for definitive association with host phenotypes. Using a combination of culture and 16S rRNA gene sequencing, referred to as culture-enriched molecular profiling, we show that the majority of the bacteria identified by 16S sequencing of the human gut microbiota can be cultured. Five fresh, anaerobic fecal samples were cultured using 33 media and incubation of plates anaerobically and aerobically resulted in 66 culture conditions for culture-enriched molecular profiling. The cultivable portion of the fecal microbiota was determined by comparing the operational taxonomic units (OTUs) recovered by 16S sequencing of the culture plates to OTUs from culture-independent sequencing of the fecal sample. Targeted isolation of Lachnospiraceae strains using conditions defined by culture-enriched molecular profiling was carried out on two fresh stool samples. We show that culture-enriched molecular profiling, utilizing 66 culture conditions combined with 16S rRNA gene sequencing, allowed for the culturing of an average of 95 % of the OTUs present at greater than 0.1 % abundance in fecal samples. Uncultured OTUs were low abundance in stool. Importantly, comparing culture-enrichment to culture-independent sequencing revealed that the majority of OTUs were detected only by culture, highlighting the advantage of culture for studying the diversity of the gut microbiota. Applying culture-enriched molecular profiling to target Lachnospiraceae strains resulted in the recovery of 79 isolates, 12 of which are on the Human Microbiome Project's "Most Wanted" list. We show that, through culture-enriched molecular profiling, the majority of the

  1. Potent Human Telomerase Inhibitors: Molecular Dynamic Simulations, Multiple Pharmacophore-Based Virtual Screening, and Biochemical Assays.

    Science.gov (United States)

    Shirgahi Talari, Faezeh; Bagherzadeh, Kowsar; Golestanian, Sahand; Jarstfer, Michael; Amanlou, Massoud

    2015-12-28

    Telomere maintenance is a universal cancer hallmark, and small molecules that disrupt telomere maintenance generally have anticancer properties. Since the vast majority of cancer cells utilize telomerase activity for telomere maintenance, the enzyme has been considered as an anticancer drug target. Recently, rational design of telomerase inhibitors was made possible by the determination of high resolution structures of the catalytic telomerase subunit from a beetle and subsequent molecular modeling of the human telomerase complex. A hybrid strategy including docking, pharmacophore-based virtual screening, and molecular dynamics simulations (MDS) were used to identify new human telomerase inhibitors. Docking methodology was applied to investigate the ssDNA telomeric sequence and two well-known human telomerase inhibitors' (BIBR1532 and MST-312) modes of interactions with hTERT TEN domain. Subsequently molecular dynamic simulations were performed to monitor and compare hTERT TEN domain, TEN-ssDNA, TEN-BIBR1532, TEN-MST-312, and TEN-ssDNA-BIBR1532 behavior in a dynamic environment. Pharmacophore models were generated considering the inhibitors manner in the TEN domain anchor site. These exploratory studies identified several new potent inhibitors whose IC50 values were generated experimentally in a low micromolar range with the aid of biochemical assays, including both the direct telomerase and the telomeric repeat amplification protocol (TRAP) assays. The results suggest that the current models of human telomerase are useful templates for rational inhibitor design.

  2. Viruses and Human Cancers: a Long Road of Discovery of Molecular Paradigms

    Science.gov (United States)

    White, Martyn K.; Pagano, Joseph S.

    2014-01-01

    SUMMARY About a fifth of all human cancers worldwide are caused by infectious agents. In 12% of cancers, seven different viruses have been causally linked to human oncogenesis: Epstein-Barr virus, hepatitis B virus, human papillomavirus, human T-cell lymphotropic virus, hepatitis C virus, Kaposi's sarcoma herpesvirus, and Merkel cell polyomavirus. Here, we review the many molecular mechanisms of oncogenesis that have been discovered over the decades of study of these viruses. We discuss how viruses can act at different stages in the complex multistep process of carcinogenesis. Early events include their involvement in mutagenic events associated with tumor initiation such as viral integration and insertional mutagenesis as well as viral promotion of DNA damage. Also involved in tumor progression is the dysregulation of cellular processes by viral proteins, and we describe how this has been investigated by studies in cell culture and in experimental animals and by molecular cellular approaches. Also important are the molecular mechanisms whereby viruses interact with the immune system and the immune evasion strategies that have evolved. PMID:24982317

  3. Development of a traceable molecular hygiene control method (TMHCM) for human DNA content in foods.

    Science.gov (United States)

    Şakalar, Ergün; Ergün, Şeyma Özçirak; Pala, Çiğdem; Akar, Emine; Ataşoğlu, Cengiz

    2017-06-15

    The aim of this study was to develop a molecular technique to determine the level of human originated DNA contamination in unhygienic food products. In the study, four model foods were prepared under both hygienic (H) and non-hygienic (NH) conditions and the human originated microbial loads of these products were determined. DNA was extracted from the model foods and human buccal samples by GIDAGEN Multi-fast DNA isolation kit. A primer specific region of human mitochondrial D-Loop was designed. The level of human DNA contamination in the model foods was determined by real-time PCR. The sensitivity of the technique developed here was 0.00001ng DNA/PCR. In addition, the applicability of the traceable molecular hygiene control method (TMHCM) was tested in 60 food samples from the market. The results of this study demonstrate that DNA based TMHCM can be used to predict to what extent foods meet the human oriented hygienic conditions. Copyright © 2016. Published by Elsevier Ltd.

  4. Contextualizing neuro-collaborations: reflections on a transdisciplinary fMRI lie detection experiment

    Science.gov (United States)

    Littlefield, Melissa M.; Fitzgerald, Des; Knudsen, Kasper; Tonks, James; Dietz, Martin J.

    2014-01-01

    Recent neuroscience initiatives (including the E.U.’s Human Brain Project and the U.S.’s BRAIN Initiative) have reinvigorated discussions about the possibilities for transdisciplinary collaboration between the neurosciences, the social sciences, and the humanities. As STS scholars have argued for decades, however, such inter- and transdisciplinary collaborations are potentially fraught with tensions between researchers. This essay build on such claims by arguing that the tensions of transdisciplinary research also exist within researchers’ own experiences of working between disciplines - a phenomenon that we call “disciplinary double consciousness” (DDC). Building on previous work that has characterized similar spaces (and especially on the Critical Neuroscience literature), we argue that “neuro-collaborations” inevitably engage researchers in DDC - a phenomenon that allows us to explore the useful dissonance that researchers can experience when working between a “home” discipline and a secondary discipline. Our case study is a five-year research project in functional magnetic resonance imaging (fMRI) lie detection involving a transdisciplinary research team made up of social scientists, a neuroscientist, and a humanist. In addition to theorizing neuro-collaborations from the inside-out, this essay presents practical suggestions for developing transdisciplinary infrastructures that could support future neuro-collaborations. PMID:24744713

  5. Contextualizing neuro-collaborations: reflections on a transdisciplinary fMRI lie detection experiment.

    Science.gov (United States)

    Littlefield, Melissa M; Fitzgerald, Des; Knudsen, Kasper; Tonks, James; Dietz, Martin J

    2014-01-01

    Recent neuroscience initiatives (including the E.U.'s Human Brain Project and the U.S.'s BRAIN Initiative) have reinvigorated discussions about the possibilities for transdisciplinary collaboration between the neurosciences, the social sciences, and the humanities. As STS scholars have argued for decades, however, such inter- and transdisciplinary collaborations are potentially fraught with tensions between researchers. This essay build on such claims by arguing that the tensions of transdisciplinary research also exist within researchers' own experiences of working between disciplines - a phenomenon that we call "disciplinary double consciousness" (DDC). Building on previous work that has characterized similar spaces (and especially on the Critical Neuroscience literature), we argue that "neuro-collaborations" inevitably engage researchers in DDC - a phenomenon that allows us to explore the useful dissonance that researchers can experience when working between a "home" discipline and a secondary discipline. Our case study is a five-year research project in functional magnetic resonance imaging (fMRI) lie detection involving a transdisciplinary research team made up of social scientists, a neuroscientist, and a humanist. In addition to theorizing neuro-collaborations from the inside-out, this essay presents practical suggestions for developing transdisciplinary infrastructures that could support future neuro-collaborations.

  6. Contextualizing Neuro-Collaborations: Reflections on a Transdisciplinary fMRI Lie Detection Experiment

    Directory of Open Access Journals (Sweden)

    Melissa M. Littlefield

    2014-03-01

    Full Text Available Recent neuroscience initiatives (including the E.U.’s Human Brain Project and the U.S.’s BRAIN Initiative have reinvigorated discussions about the possibilities for transdisciplinary collaboration between the neurosciences, the social sciences, and the humanities. As STS scholars have argued for decades, however, such inter- and transdisciplinary collaborations are potentially fraught with tensions between researchers. This essay build on such claims by arguing that the tensions of transdisciplinary research also exist within researchers’ own experiences of working between disciplines – a phenomenon that we call ‘Disciplinary Double Consciousness’ (DDC. Building on previous work that has characterized similar spaces (and especially on the Critical Neuroscience literature, we argue that ‘neuro-collaborations’ inevitably engage researchers in DDC – a phenomenon that allows us to explore the useful dissonance that researchers can experience when working between a home discipline and a secondary discipline. Our case study is a five-year case study in fMRI lie detection involving a transdisciplinary research team made up of social scientists, a neuroscientist, and a humanist. In addition to theorizing neuro-collaborations from the inside-out, this essay presents practical suggestions for developing transdisciplinary infrastructures that could support future neuro-collaborations.

  7. Neuro-fuzzy models for systems identification applied to the operation of nuclear power plants; Sistemas neuro-fuzzy para identificacao de sistemas aplicados a operacao de centrais nucleares

    Energy Technology Data Exchange (ETDEWEB)

    Alves, Antonio Carlos Pinto Dias

    2000-09-01

    A nuclear power plant has a myriad of complex system and sub-systems that, working cooperatively, make the control of the whole plant. Nevertheless their operation be automatic most of the time, the integral understanding of their internal- logic can be away of the comprehension of even experienced operators because of the poor interpretability those controls offer. This difficulty does not happens only in nuclear power plants but in almost every a little more complex control system. Neuro-fuzzy models have been used for the last years in a attempt of suppress these difficulties because of their ability of modelling in linguist form even a system which behavior is extremely complex. This is a very intuitive human form of interpretation and neuro-fuzzy model are gathering increasing acceptance. Unfortunately, neuro-fuzzy models can grow up to become of hard interpretation because of the complexity of the systems under modelling. In general, that growing occurs in function of redundant rules or rules that cover a very little domain of the problem. This work presents an identification method for neuro-fuzzy models that not only allows models grow in function of the existent complexity but that beforehand they try to self-adapt to avoid the inclusion of new rules. This form of construction allowed to arrive to highly interpretative neuro-fuzzy models even of very complex systems. The use of this kind of technique in modelling the control of the pressurizer of a PWR nuclear power plant allowed verify its validity and how neuro-fuzzy models so built can be useful in understanding the automatic operation of a nuclear power plant. (author)

  8. Molecular Insights into Fully Human and Humanized Monoclonal Antibodies: What are the Differences and Should Dermatologists Care?

    Science.gov (United States)

    Mallbris, Lotus; Davies, Julian; Glasebrook, Andrew; Tang, Ying; Glaesner, Wolfgang; Nickoloff, Brian J

    2016-07-01

    In recent years, a large number of therapeutic monoclonal antibodies have come to market to treat a variety of conditions including patients with immune-mediated chronic inflammation. Distinguishing the relative clinical efficacy and safety profiles of one monoclonal antibody relative to another can be difficult and complex due to different clinical designs and paucity of head-to-head comparator studies. One distinguishing feature in interpreting clinical trial data by dermatologists may begin by determining whether a monoclonal antibody is fully human or humanized, which can be discerned by the generic name of the drug. Herein, this commentary highlights the distinctions and similarities of fully human and humanized monoclonal antibodies in their nomenclature, engineering, and clinical profiles. While there are a number of differences between these types of monoclonal antibodies, current evidence indicates that this designation does not impart any measurable impact on overall clinical efficacy and safety profiles of a given drug. Based on molecular insights provided in this commentary, it is clear that each monoclonal antibody, irrespective of being fully human or humanized, should be individually assessed for its clinical impact regarding safety and efficacy. Going beyond the type of generic name ascribed to a monoclonal antibody will be an ever-increasing theme for dermatologists as more therapeutic monoclonal antibodies emerge to potentially treat a wider scope of diseases with cutaneous manifestations.

  9. Binding of Citreoviridin to Human Serum Albumin: Multispectroscopic and Molecular Docking

    Directory of Open Access Journals (Sweden)

    Haifeng Hou

    2015-01-01

    Full Text Available Citreoviridin (CIT, a mycotoxin produced by Penicillium citreonigrum, is a common contaminant of wide range of agriproducts and detrimental to human and animal health. In this study, the interaction of CIT with human serum albumin (HSA is researched by steady-state fluorescence, ultraviolet-visible (UV-Vis absorption, circular dichroism (CD methods, and molecular modeling. The association constants, binding site numbers, and corresponding thermodynamic parameters are used to investigate the quenching mechanism. The alternations of HSA secondary structure in the presence of CIT are demonstrated with UV-Vis, synchronous fluorescence, and CD spectra. The molecular modeling results reveal that CIT can bind with hydrophobic pocket of HSA with hydrophobic and hydrogen bond force. Moreover, an apparent distance of 3.25 nm between Trp214 and CIT is obtained via fluorescence resonance energy transfer method.

  10. Exploration of Novel Human Tyrosinase Inhibitors by Molecular Modeling, Docking and Simulation Studies.

    Science.gov (United States)

    Hassan, Mubashir; Ashraf, Zaman; Abbas, Qamar; Raza, Hussain; Seo, Sung-Yum

    2016-04-21

    Research studies on human tyrosinase inhibitors and exploration for better cytotoxic agents remain an important line in drug discovery and development at the present time. Recently, multiple inhibitors are being used to cure melanogenesis by targeting human tyrosinase. A series of coumarin (C1-C9)-, thymol (T1-T8)- and vanillin (V1-V8)-based derivatives have been theoretically analyzed for their inhibitory effects against human tyrosinase. The crystal structure of human tyrosinase is not available in Protein Data Bank. Therefore, homology modeling approach was used to predict three-dimensional (3D) crystal structure of human tyrosinase. The reliability and efficacy of predicted 3D structure were validated by using Ramachandran plots which indicate that 95.01 % residues are present in favored regions. Moreover, multiple computational approaches such as molecular docking and molecular dynamic (MD) simulation along with various online tools were employed to screen the best inhibitor against melanogenesis. The results revealed that V7 and C9 compounds showed significant binding energy values (-7.79 and -7.40 kcal/mol, respectively) compared with the standard drugs such as kojic acid (-4.21 kcal/mol) and arbutin (-4.62 kcal/mol). Moreover, MD simulation results also justified that V7 showed little fluctuations throughout the simulation period as depicted by the root mean square deviation and root mean square fluctuation graphs. Thus, the present in silico study provides a deeper insight into the structural attributes of V7 compound and its overall molecular interactions against human tyrosinase and gives a hypothetical gateway to use this compound as a potential inhibitor against melanogenesis.

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

    Directory of Open Access Journals (Sweden)

    He Liu

    2016-01-01

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

  12. MOLECULAR IDENTIFICATION OF Pseudoterranova azarasi LARVAE IN COD (Gadus sp. SOLD FOR HUMAN CONSUMPTION IN BRAZIL

    Directory of Open Access Journals (Sweden)

    Juliana MARIGO

    2015-12-01

    Full Text Available Anisakiasis and Pseudoterranovosis are human diseases caused by the ingestion of live Anisakidae larvae in raw, undercooked or lightly marinated fish. Larvae were collected from one salted cod sold for human consumption in a Sao Paulo market in 2013. One section of one brownish larva was used for molecular analyses. The partial COX2 gene sequence from the larva had a nucleotide identity of 99.8 % with Pseudoterranova azarasi, which belongs to the Pseudoterranova decipiens species complex. The risk of allergy when consuming dead larvae in salted fish is not well known and should be considered.

  13. Paraneoplastic Syndromes in Neuro-Ophthalmology.

    Science.gov (United States)

    Gordon, Lynn K

    2015-09-01

    Paraneoplastic syndromes that affect the visual pathways and present with neuro-ophthalmologic signs or symptoms may involve the afferent or efferent systems. Afferent syndromes may involve the optic nerve or retina and, in some cases, these may be associated with systemic neurologic disease. Efferent symptoms typically affect eye movements and may involve the neuromuscular junction or involuntary eye movements. Literature review and personal clinical and research experience. Diagnosis of paraneoplastic syndromes relies on clinical and laboratory evaluations. In the appropriate clinical setting, the presence of specific antibodies may help confirm the diagnosis. In some cases, the visual pathway disturbance precedes a diagnosis of malignancy. Astute observation and selective evaluation and management are critical to establish the correct diagnosis and institute therapeutic approaches that can be sight or life saving.

  14. Neuro-oncology biotech industry progress report.

    Science.gov (United States)

    Chakraborty, Shamik; Bodhinayake, Imithri; Chiluwal, Amrit; Langer, David J; Ruggieri, Rosamaria; Symons, Marc; Boockvar, John A

    2016-05-01

    The Brain Tumor Biotech Center at the Feinstein Institute for Medical Research, in collaboration with Voices Against Brain Cancer hosted The Brain Tumor Biotech Summit at in New York City in June 2015. The focus was once again on fostering collaboration between neuro-oncologist, neurosurgeons, scientists, leaders from biotechnology and pharmaceutical industries, and members of the financial community. The summit highlighted the recent advances in the treatment of brain tumor, and specifically focused on targeting of stem cells and EGFR, use of prophage and immunostimulatory vaccines, retroviral vectors for drug delivery, biologic prodrug, Cesium brachytherapy, and use of electric field to disrupt tumor cell proliferation. This article summarizes the current progress in brain tumor research as presented at 2015 The Brain Tumor Biotech Summit.

  15. Diagnostic imaging in neuro-ophthalmology.

    Science.gov (United States)

    Vela Marín, A C; Seral Moral, P; Bernal Lafuente, C; Izquierdo Hernández, B

    2018-01-20

    Neuro-ophthalmology is a field combining neurology and ophthalmology that studies diseases that affect the visual system and the mechanisms that control eye movement and pupil function. Imaging tests make it possible to thoroughly assess the relevant anatomy and disease of the structures that make up the visual pathway, the nerves that control eye and pupil movement, and the orbital structures themselves. This article is divided into three sections (review of the anatomy, appropriate imaging techniques, and evaluation of disease according to clinical symptoms), with the aim of providing useful tools that will enable radiologists to choose the best imaging technique for the differential diagnosis of patients' problems to reach the correct diagnosis of their disease. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. The Danish Neuro-Oncology Registry

    DEFF Research Database (Denmark)

    Hansen, Steinbjørn; Nielsen, Jan; Laursen, René J

    2016-01-01

    BACKGROUND: The Danish Neuro-Oncology Registry (DNOR) is a nationwide clinical cancer database that has prospectively registered data on patients with gliomas since January 2009. The purpose of this study was to describe the establishment of the DNOR and further to evaluate the database...... Pathology Registry. The data validity of important clinical variables was evaluated by a random sample of 100 patients from the DNOR using the medical records as reference. RESULTS: A total of 2241 patients were registered in the DNOR by December 2014 with an overall patient completeness of 92 %, which...... of patient registration was very high (92 %) and the validity of the most important patient data was good. The DNOR is a newly established national database, which is a reliable source for future scientific studies and clinical quality assessments among patients with gliomas....

  17. Designing Flexible Neuro-Fuzzy System Based on Sliding Mode Controller for Magnetic Levitation Systems

    OpenAIRE

    Zahra Mohammadi; Mohammad Teshnehlab; Mahdi Aliyari Shoorehdeli

    2011-01-01

    This study presents a novel controller of magnetic levitation system by using new neuro-fuzzy structures which called flexible neuro-fuzzy systems. In this type of controller we use sliding mode control with neuro-fuzzy to eliminate the Jacobian of plant. At first, we control magnetic levitation system with Mamdanitype neuro-fuzzy systems and logical-type neuro-fuzzy systems separately and then we use two types of flexible neuro-fuzzy systems as controllers. Basic flexible OR-type neuro-fuzzy...

  18. Potential human cholesterol esterase inhibitor design: benefits from the molecular dynamics simulations and pharmacophore modeling studies.

    Science.gov (United States)

    John, Shalini; Thangapandian, Sundarapandian; Lee, Keun Woo

    2012-01-01

    Human pancreatic cholesterol esterase (hCEase) is one of the lipases found to involve in the digestion of large and broad spectrum of substrates including triglycerides, phospholipids, cholesteryl esters, etc. The presence of bile salts is found to be very important for the activation of hCEase. Molecular dynamic simulations were performed for the apoform and bile salt complexed form of hCEase using the co-ordinates of two bile salts from bovine CEase. The stability of the systems throughout the simulation time was checked and two representative structures from the highly populated regions were selected using cluster analysis. These two representative structures were used in pharmacophore model generation. The generated pharmacophore models were validated and used in database screening. The screened hits were refined for their drug-like properties based on Lipinski's rule of five and ADMET properties. The drug-like compounds were further refined by molecular docking simulation using GOLD program based on the GOLD fitness score, mode of binding, and molecular interactions with the active site amino acids. Finally, three hits of novel scaffolds were selected as potential leads to be used in novel and potent hCEase inhibitor design. The stability of binding modes and molecular interactions of these final hits were re-assured by molecular dynamics simulations.

  19. Effects of phenylpropanolamine (PPA) on in vitro human erythrocyte membranes and molecular models

    Energy Technology Data Exchange (ETDEWEB)

    Suwalsky, Mario, E-mail: msuwalsk@udec.cl [Faculty of Chemical Sciences, University of Concepcion, Concepcion (Chile); Zambrano, Pablo; Mennickent, Sigrid [Faculty of Pharmacy, University of Concepcion, Concepcion (Chile); Villena, Fernando [Faculty of Biological Sciences, University of Concepcion, Concepcion (Chile); Sotomayor, Carlos P.; Aguilar, Luis F. [Instituto de Quimica, Pontificia Universidad Catolica de Valparaiso, Valparaiso (Chile); Bolognin, Silvia [CNR-Institute for Biomedical Technologies, University of Padova, Padova (Italy)

    2011-03-18

    Research highlights: {yields} PPA is a common ingredient in cough-cold medication and appetite suppressants. {yields} Reports on its effects on human erythrocytes are very scarce. {yields} We found that PPA induced in vitro morphological changes to human erythrocytes. {yields} PPA interacted with isolated unsealed human erythrocyte membranes. {yields} PPA interacted with class of lipid present in the erythrocyte membrane outer monolayer. -- Abstract: Norephedrine, also called phenylpropanolamine (PPA), is a synthetic form of the ephedrine alkaloid. After reports of the occurrence of intracranial hemorrhage and other adverse effects, including several deaths, PPA is no longer sold in USA and Canada. Despite the extensive information about PPA toxicity, reports on its effects on cell membranes are scarce. With the aim to better understand the molecular mechanisms of the interaction of PPA with cell membranes, ranges of concentrations were incubated with intact human erythrocytes, isolated unsealed human erythrocyte membranes (IUM), and molecular models of cell membranes. The latter consisted in bilayers built-up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), phospholipid classes present in the outer and inner monolayers of most plasmatic cell membranes, respectively. The capacity of PPA to perturb the bilayer structures of DMPC and DMPE was assessed by X-ray diffraction, DMPC large unilamellar vesicles (LUV) and IUM were studied by fluorescence spectroscopy, and intact human erythrocytes were observed by scanning electron microscopy (SEM). This study presents evidence that PPA affects human red cell membranes as follows: (a) in SEM studies on human erythrocytes it was observed that 0.5 mM PPA induced shape changes; (b) in IUM PPA induced a sharp decrease in the fluorescence anisotropy in the lipid bilayer acyl chains in a concentration range lower than 100 {mu}M; (c) X-ray diffraction studies showed that PPA in the 0.1-0.5 m

  20. Novel insights from genetic and molecular characterization of the human clock.

    Science.gov (United States)

    Ptácek, L J; Jones, C R; Fu, Y-H

    2007-01-01

    Biological rhythms govern the ebb and flow of life on planet Earth. Animals have an internal timekeeping mechanism that precisely regulates 24-hour rhythms of body function and behavior and synchronizes them to the day/night cycle. Circadian pacemakers trigger behavioral and physiological processes that dictate our daily rhythms. Despite the importance of the circadian clock to all aspects of our physiology and behavior, the opportunity to probe the human circadian clock only recently became possible with the recognition of Mendelian circadian variants in people (familial advanced sleep phase syndrome, FASPS). We have now cloned several genes and identified mutations causing FASPS. Study of these genes and the proteins they encode and engineering of the human mutations into mouse models are allowing study of this fascinating phenotype and yielding novel insights into circadian regulation in humans. Ultimately, such work will allow us to understand the similarities and differences between the human clock and those of model organisms. In addition, recent studies have also linked disruption of the circadian clock with numerous ailments, including cancer, cardiovascular diseases, asthma, and learning disorders. Thus, studying the molecular mechanism of human circadian rhythmicity will have an enormous impact on our understanding of human health and disease. It should also lead to new strategies for pharmacological manipulation of the human clock to improve the treatment of jet lag, various clock-related sleep and psychiatric disorders, and other human diseases.

  1. Neuro-inflammation, blood-brain barrier, seizures and autism

    Directory of Open Access Journals (Sweden)

    Theoharides Theoharis C

    2011-11-01

    Full Text Available Abstract Many children with Autism Spectrum Diseases (ASD present with seizure activity, but the pathogenesis is not understood. Recent evidence indicates that neuro-inflammation could contribute to seizures. We hypothesize that brain mast cell activation due to allergic, environmental and/or stress triggers could lead to focal disruption of the blood-brain barrier and neuro-inflammation, thus contributing to the development of seizures. Treating neuro-inflammation may be useful when anti-seizure medications are ineffective.

  2. Antibody humanization by molecular dynamics simulations-in-silico guided selection of critical backmutations.

    Science.gov (United States)

    Margreitter, Christian; Mayrhofer, Patrick; Kunert, Renate; Oostenbrink, Chris

    2016-06-01

    Monoclonal antibodies represent the fastest growing class of biotherapeutic proteins. However, as they are often initially derived from rodent organisms, there is a severe risk of immunogenic reactions, hampering their applicability. The humanization of these antibodies remains a challenging task in the context of rational drug design. "Superhumanization" describes the direct transfer of the complementarity determining regions to a human germline framework, but this humanization approach often results in loss of binding affinity. In this study, we present a new approach for predicting promising backmutation sites using molecular dynamics simulations of the model antibody Ab2/3H6. The simulation method was developed in close conjunction with novel specificity experiments. Binding properties of mAb variants were evaluated directly from crude supernatants and confirmed using established binding affinity assays for purified antibodies. Our approach provides access to the dynamical features of the actual binding sites of an antibody, based solely on the antibody sequence. Thus we do not need structural data on the antibody-antigen complex and circumvent cumbersome methods to assess binding affinities. © 2016 The Authors Journal of Molecular Recognition Published by John Wiley & Sons Ltd. © 2016 The Authors Journal of Molecular Recognition Published by John Wiley & Sons Ltd.

  3. Molecular structure-affinity relationship of bufadienolides and human serum albumin in vitro and molecular docking analysis.

    Directory of Open Access Journals (Sweden)

    Jing Zhou

    Full Text Available The development of bufadienolides as anti-tumor agents is limited due to poor pharmacokinetic properties regarding drug half-lives and toxicity in vivo. These serious factors might be improved by increasing the drug/albumin-binding ratio. This study therefore investigated the relationship between the structural properties of nine bufadienolides and their affinities for human serum albumin (HSA by a fluorescence spectroscopy-based analysis and molecular docking. Fluorescence quenching data showed that the interaction of each bufadienolide with HSA formed a non-fluorescent complex, while thermodynamic parameters revealed negative ΔS and ΔH values, corresponding to changes in enthalpy and entropy, respectively. The structural differences between the various bufadienolides markedly influenced their binding affinity for HSA. With the exception of a C = O bond at the C12 position that decreased the binding affinity for HSA, other polar groups tended to increase the affinity, especially a hydroxyl (OH group at assorted bufadienolide sites. The rank order of binding affinities for drugs with tri-hydroxyl groups was as follows: 11-OH > 5-OH > 16-OH; in addition, 16-acetoxy (OAc, 10-aldehyde and 14-epoxy constituents notably enhanced the binding affinity. Among these groups, 11-OH and 16-acetyl were especially important for a seamless interaction between the bufadienolides and HSA. Furthermore, molecular docking analysis revealed that either an 11-OH or a 16-OAc group spatially close to a five-membered lactone ring significantly facilitated the anchoring of these compounds within site I of the HSA pocket via hydrogen bonding (H-bonding with Tyr150 or Lys199, respectively. In summary, bufadienolide structure strongly affects binding with HSA, and 11-OH or 16-OAc groups improve the drug association with key amino acid residues. This information is valuable for the prospective development of bufadienolides with improved pharmacological profiles as novel

  4. A novel minimally-invasive method to sample human endothelial cells for molecular profiling.

    Directory of Open Access Journals (Sweden)

    Stephen W Waldo

    Full Text Available The endothelium is a key mediator of vascular homeostasis and cardiovascular health. Molecular research on the human endothelium may provide insight into the mechanisms underlying cardiovascular disease. Prior methodology used to isolate human endothelial cells has suffered from poor yields and contamination with other cell types. We thus sought to develop a minimally invasive technique to obtain endothelial cells derived from human subjects with higher yields and purity.Nine healthy volunteers underwent endothelial cell harvesting from antecubital veins using guidewires. Fluorescence-activated cell sorting (FACS was subsequently used to purify endothelial cells from contaminating cells using endothelial surface markers (CD34/CD105/CD146 with the concomitant absence of leukocyte and platelet specific markers (CD11b/CD45. Endothelial lineage in the purified cell population was confirmed by expression of endothelial specific genes and microRNA using quantitative polymerase chain reaction (PCR.A median of 4,212 (IQR: 2161-6583 endothelial cells were isolated from each subject. Quantitative PCR demonstrated higher expression of von Willebrand Factor (vWF, P<0.001, nitric oxide synthase 3 (NOS3, P<0.001 and vascular cell adhesion molecule 1 (VCAM-1, P<0.003 in the endothelial population compared to similarly isolated leukocytes. Similarly, the level of endothelial specific microRNA-126 was higher in the purified endothelial cells (P<0.001.This state-of-the-art technique isolates human endothelial cells for molecular analysis in higher purity and greater numbers than previously possible. This approach will expedite research on the molecular mechanisms of human cardiovascular disease, elucidating its pathophysiology and potential therapeutic targets.

  5. A novel antibody humanization method based on epitopes scanning and molecular dynamics simulation.

    Science.gov (United States)

    Zhang, Ding; Chen, Cai-Feng; Zhao, Bin-Bin; Gong, Lu-Lu; Jin, Wen-Jing; Liu, Jing-Jun; Wang, Jing-Fei; Wang, Tian-Tian; Yuan, Xiao-Hui; He, You-Wen

    2013-01-01

    1-17-2 is a rat anti-human DEC-205 monoclonal antibody that induces internalization and delivers antigen to dendritic cells (DCs). The potentially clinical application of this antibody is limited by its murine origin. Traditional humanization method such as complementarity determining regions (CDRs) graft often leads to a decreased or even lost affinity. Here we have developed a novel antibody humanization method based on computer modeling and bioinformatics analysis. First, we used homology modeling technology to build the precise model of Fab. A novel epitope scanning algorithm was designed to identify antigenic residues in the framework regions (FRs) that need to be mutated to human counterpart in the humanization process. Then virtual mutation and molecular dynamics (MD) simulation were used to assess the conformational impact imposed by all the mutations. By comparing the root-mean-square deviations (RMSDs) of CDRs, we found five key residues whose mutations would destroy the original conformation of CDRs. These residues need to be back-mutated to rescue the antibody binding affinity. Finally we constructed the antibodies in vitro and compared their binding affinity by flow cytometry and surface plasmon resonance (SPR) assay. The binding affinity of the refined humanized antibody was similar to that of the original rat antibody. Our results have established a novel method based on epitopes scanning and MD simulation for antibody humanization.

  6. 2nd International Conference on NeuroRehabilitation

    CERN Document Server

    Andersen, Ole; Akay, Metin

    2014-01-01

    The book is the proceedings of the 2nd International Conference on NeuroRehabilitation (ICNR 2014), held 24th-26th June 2014 in Aalborg, Denmark. The conference featured the latest highlights in the emerging and interdisciplinary field of neural rehabilitation engineering and identified important healthcare challenges the scientific community will be faced with in the coming years. Edited and written by leading experts in the field, the book includes keynote papers, regular conference papers, and contributions to special and innovation sessions, covering the following main topics: neuro-rehabilitation applications and solutions for restoring impaired neurological functions; cutting-edge technologies and methods in neuro-rehabilitation; and translational challenges in neuro-rehabilitation. Thanks to its highly interdisciplinary approach, the book will not only be a  highly relevant reference guide for academic researchers, engineers, neurophysiologists, neuroscientists, physicians and physiotherapists workin...

  7. Perspectives on psycho-neuro-immunology in oncology

    Directory of Open Access Journals (Sweden)

    Vallath Nandini

    2006-01-01

    Full Text Available Psycho-oncology and psycho-neuro-immunology are both powerful new disciplines. Although a lot of literature exists in both of these fields the evidence is often controversial. This paper gives a brief perspective on the origins of psycho-neuro-immunology and discusses how our current understanding of this subject can be translated into clinical practice in an Indian setting.

  8. Neuroæstetik eller kunst på hjernen

    DEFF Research Database (Denmark)

    Clasen, Mathias

    2009-01-01

    Neuroæstetikken kombinerer hjerneforskning, æstetikforskning og eksperimentel psykologi -- alt sammen for at forstå en af Homo sapiens' mest bizarre hobbyer: kunst. Forskning i kunstens neurobiologi griber om sig.......Neuroæstetikken kombinerer hjerneforskning, æstetikforskning og eksperimentel psykologi -- alt sammen for at forstå en af Homo sapiens' mest bizarre hobbyer: kunst. Forskning i kunstens neurobiologi griber om sig....

  9. Aplikasi Neuro Fuzzy Controller Pada Sistem Titrasi Pengolah Limbah Cair

    OpenAIRE

    Fatkhurrozi, Bagus

    2007-01-01

    This research is aimed at planning and measuriang the system of liquid waste processing devide with ply neutral reaction that is controlled by computer based on neuro fuzzy controller, in which the system control is fuzzy logical system than can improve control out put response based on nervous net imitation. In this system, it can be seen that computer has a very important role that is to control the proless of all activities in waste processing. Key ward. PH, Neuro fuzzy controller

  10. Molecular cloning and expression of the human Δ7-sterol reductase

    Science.gov (United States)

    Moebius, Fabian F.; Fitzky, Barbara U.; Lee, Joon No; Paik, Young-Ki; Glossmann, Hartmut

    1998-01-01

    Inhibitors of the last steps of cholesterol biosynthesis such as AY9944 and BM15766 severely impair brain development. Their molecular target is the Δ7-sterol reductase (EC 1.3.1.21), suspected to be defective in the Smith–Lemli–Opitz syndrome, a frequent inborn disorder of sterol metabolism. Molecular cloning of the cDNA revealed that the human enzyme is a membrane-bound protein with a predicted molecular mass of 55 kDa and six to nine putative transmembrane segments. The protein is structurally related to plant and yeast sterol reductases. In adults the ubiquitously transcribed mRNA is most abundant in adrenal gland, liver, testis, and brain. The Δ7-sterol reductase is the ultimate enzyme of cholesterol biosynthesis in vertebrates and is absent from yeast. Microsomes from Saccharomyces cerevisiae strains heterologously expressing the human cDNA remove the C7–8 double bond in 7-dehydrocholesterol. The conversion to cholesterol depends on NADPH and is potently inhibited by AY9944 (IC50 0.013 μM), BM15766 (IC50 1.2 μM), and triparanol (IC50 14 μM). Our work paves the way to clarify whether a defect in the Δ7-sterol reductase gene underlies the Smith–Lemli–Opitz syndrome. PMID:9465114

  11. Molecular Paleoparasitological Hybridization Approach as Effective Tool for Diagnosing Human Intestinal Parasites from Scarce Archaeological Remains

    Science.gov (United States)

    Jaeger, Lauren Hubert; Iñiguez, Alena Mayo

    2014-01-01

    Paleoparasitology is the science that uses parasitological techniques for diagnosing parasitic diseases in the past. Advances in molecular biology brought new insights into this field allowing the study of archaeological material. However, due to technical limitations a proper diagnosis and confirmation of the presence of parasites is not always possible, especially in scarce and degraded archaeological remains. In this study, we developed a Molecular Paleoparasitological Hybridization (MPH) approach using ancient DNA (aDNA) hybridization to confirm and complement paleoparasitological diagnosis. Eight molecular targets from four helminth parasites were included: Ascaris sp., Trichuris trichiura, Enterobius vermicularis, and Strongyloides stercoralis. The MPH analysis using 18th century human remains from Praça XV cemetery (CPXV), Rio de Janeiro, Brazil, revealed for the first time the presence E. vermicularis aDNA (50%) in archaeological sites of Brazil. Besides, the results confirmed T. trichiura and Ascaris sp. infections. The prevalence of infection by Ascaris sp. and E. vermicularis increased considerably when MPH was applied. However, a lower aDNA detection of T. trichiura (40%) was observed when compared to the diagnosis by paleoparasitological analysis (70%). Therefore, based on these data, we suggest a combination of Paleoparasitological and MPH approaches to verify the real panorama of intestinal parasite infection in human archeological samples. PMID:25162694

  12. Lessons learned with molecular methods targeting the BCSP-31 membrane protein for diagnosis of human brucellosis.

    Science.gov (United States)

    Sanjuan-Jimenez, Rocio; Colmenero, Juan D; Morata, Pilar

    2017-06-01

    Brucellosis remains an emerging and re-emerging zoonosis worldwide causing high human morbidity. It usually affects persons who are permanently exposed to fastidious microorganisms of the Brucella genus and has a nonspecific clinical picture. Thus, diagnosis of brucellosis can sometimes be difficult. Molecular techniques have recently been found very useful in the diagnosis of brucellosis together with its common and very diverse focal complications. We herein review all the lessons learned by our group concerning the molecular diagnosis of human brucellosis over the last twenty years. The results, initially using one-step conventional PCR, later PCR-ELISA and more recently real-time PCR, using both fluorescent intercalating reagents (SYBR-Green I) and specific probes (Taqman), have shown that these techniques are all much more sensitive than bacteriological methods and more specific than the usual serological techniques for the diagnosis of primary infection, the post-treatment control of the disease, early detection of relapse and the diagnosis of focal complications. Optimization of the technique and improvements introduced over the years show that molecular methods, currently accessible for most clinical laboratories, enable easy rapid diagnosis of brucellosis at the same time as they avoid any risk to laboratory personnel while handling live Brucella spp. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Neuro-Otological and Peripheral Nerve Involvement in Fabry Disease.

    Science.gov (United States)

    Carmona, Sergio; Weinschelbaum, Romina; Pardal, Ana; Marchesoni, Cintia; Zuberbuhler, Paz; Acosta, Patricia; Cáceres, Guillermo; Kisinovsky, Isaac; Bayón, Luciana; Reisin, Ricardo

    2017-07-18

    Fabry disease (FD) is an X-linked lysosomal storage disease, with multisystemic glycosphingolipids deposits. Neuro-otological involvement leading to hearing loss and vestibular dysfunctions has been described, but there is limited information about the frequency, site of lesion, or the relationship with peripheral neuropathy. The aim was to evaluate the presence of auditory and vestibular symptoms, and assess neurophysiological involvement of the VIII cranial nerve, correlating these findings with clinical and neurophysiological features of peripheral neuropathy. We studied 36 patients with FD with a complete neurological and neuro-otological evaluation including nerve conduction studies, quantitative sensory testing (to evaluate small fiber by warm and cold threshold detection and cold and heat pain), vestibular evoked myogenic potentials, videonistagmography, audiometry and brainstem auditory evoked potentials. Neuro-otologic symptoms included hearing loss (22.2%), vertigo (27.8%) or both (25%). An involvement of either cochlear or vestibular function was identified in most patients (75%). In 70% of our patients the involvement of both cochlear and vestibular function could not be explained by a neural or vascular mechanism. Small fiber neuropathy was identified in 77.7%. There were no significant associations between neuro-otological and QST abnormalities. Neuro-otologic involvement is frequent and most likely under-recognized in patients with FD. It lacks a specific neural or vascular pattern, suggesting multi-systemic, end organ damage. Small fiber neuropathy is an earlier manifestation of FD, but there is no correlation between the development of neuropathy and neuro-otological abnormalities.

  14. Insights into the binding of thiosemicarbazone derivatives with human serum albumin: spectroscopy and molecular modelling studies.

    Science.gov (United States)

    Karthikeyan, Subramani; Bharanidharan, Ganesan; Kesherwani, Manish; Mani, Karthik Ananth; Srinivasan, Narasimhan; Velmurugan, Devadasan; Aruna, Prakasarao; Ganesan, Singaravelu

    2016-06-01

    4-[(1Z)-1-(2-carbamothioylhydrazinylidene)ethyl]phenyl acetate [Ace semi],4-[(1Z)-1-(2-carbamothioylhydrazinylidene)ethyl]phenyl propanoate [Pro semi] from the family of thiosemicarbazones derivative has been newly synthesized. It has good anticancer activity as well as antibacterial and it is also less toxic in nature, its binding characteristics are therefore of huge interest for understanding pharmacokinetic mechanism of the drug. The binding of thiosemicarbazone derivative to human serum albumin (HSA) has been investigated by studying its quenching mechanism, binding kinetics and the molecular distance (r) between donor (HSA) and acceptor (thiosemicarbazone derivative) was estimated according to Forster's theory of non-radiative energy transfer using fluorescence spectroscopy. The binding dynamics has been elaborated using synchronous fluorescence spectroscopy, and the feature of thiosemicarbazone derivative induced structural changes of HSA has been studied by circular dichorism, Fourier transform infrared spectroscopy. Molecular modelling simulations explore the hydrophobic interaction and hydrogen bonding which stabilizes the interaction.

  15. Human heterotaxy syndrome – from molecular genetics to clinical features, management, and prognosis – .

    Science.gov (United States)

    Shiraishi, Isao; Ichikawa, Hajime

    2012-01-01

    Human heterotaxy syndrome is characterized by a wide variety of cardiac and extracardiac congenital malformations that are primarily induced by disorders of the left-right axis determination during early embryonic development. The cellular and molecular mechanisms of the left-right asymmetry have been extensively investigated in the past decade and the developmental mechanisms of the syndrome have been considerably elucidated. Medical and surgical management and treatment of heterotaxy syndrome have advanced as well. However, prognosis of the disease still remains unsatisfactory because the syndrome is often associated with a combination of complicated congenital heart diseases. Management of heterotaxy patients, particularly those who have undergone the Fontan procedure, is now one of the most important issues in pediatric and adult congenital heart disease clinics. In this review, we focus on the recent advances in knowledge of the genetic and molecular pathogenesis of heterotaxy syndrome, as well as its clinical features, management, and prognosis.

  16. NeuroPlace: Categorizing urban places according to mental states.

    Science.gov (United States)

    Al-Barrak, Lulwah; Kanjo, Eiman; Younis, Eman M G

    2017-01-01

    Urban spaces have a great impact on how people's emotion and behaviour. There are number of factors that impact our brain responses to a space. This paper presents a novel urban place recommendation approach, that is based on modelling in-situ EEG data. The research investigations leverages on newly affordable Electroencephalogram (EEG) headsets, which has the capability to sense mental states such as meditation and attention levels. These emerging devices have been utilized in understanding how human brains are affected by the surrounding built environments and natural spaces. In this paper, mobile EEG headsets have been used to detect mental states at different types of urban places. By analysing and modelling brain activity data, we were able to classify three different places according to the mental state signature of the users, and create an association map to guide and recommend people to therapeutic places that lessen brain fatigue and increase mental rejuvenation. Our mental states classifier has achieved accuracy of (%90.8). NeuroPlace breaks new ground not only as a mobile ubiquitous brain monitoring system for urban computing, but also as a system that can advise urban planners on the impact of specific urban planning policies and structures. We present and discuss the challenges in making our initial prototype more practical, robust, and reliable as part of our on-going research. In addition, we present some enabling applications using the proposed architecture.

  17. NeuroPlace: Categorizing urban places according to mental states.

    Directory of Open Access Journals (Sweden)

    Lulwah Al-Barrak

    Full Text Available Urban spaces have a great impact on how people's emotion and behaviour. There are number of factors that impact our brain responses to a space. This paper presents a novel urban place recommendation approach, that is based on modelling in-situ EEG data. The research investigations leverages on newly affordable Electroencephalogram (EEG headsets, which has the capability to sense mental states such as meditation and attention levels. These emerging devices have been utilized in understanding how human brains are affected by the surrounding built environments and natural spaces. In this paper, mobile EEG headsets have been used to detect mental states at different types of urban places. By analysing and modelling brain activity data, we were able to classify three different places according to the mental state signature of the users, and create an association map to guide and recommend people to therapeutic places that lessen brain fatigue and increase mental rejuvenation. Our mental states classifier has achieved accuracy of (%90.8. NeuroPlace breaks new ground not only as a mobile ubiquitous brain monitoring system for urban computing, but also as a system that can advise urban planners on the impact of specific urban planning policies and structures. We present and discuss the challenges in making our initial prototype more practical, robust, and reliable as part of our on-going research. In addition, we present some enabling applications using the proposed architecture.

  18. A cascaded neuro-computational model for spoken word recognition

    Science.gov (United States)

    Hoya, Tetsuya; van Leeuwen, Cees

    2010-03-01

    In human speech recognition, words are analysed at both pre-lexical (i.e., sub-word) and lexical (word) levels. The aim of this paper is to propose a constructive neuro-computational model that incorporates both these levels as cascaded layers of pre-lexical and lexical units. The layered structure enables the system to handle the variability of real speech input. Within the model, receptive fields of the pre-lexical layer consist of radial basis functions; the lexical layer is composed of units that perform pattern matching between their internal template and a series of labels, corresponding to the winning receptive fields in the pre-lexical layer. The model adapts through self-tuning of all units, in combination with the formation of a connectivity structure through unsupervised (first layer) and supervised (higher layers) network growth. Simulation studies show that the model can achieve a level of performance in spoken word recognition similar to that of a benchmark approach using hidden Markov models, while enabling parallel access to word candidates in lexical decision making.

  19. Neuro degenerative diseases: clinical concerns; Les maladies neuro-degeneratives: problemes cliniques

    Energy Technology Data Exchange (ETDEWEB)

    Ibanez, V. [Hopitaux Universitaires de Geneve (HUG), Unite de Neuroimagerie, Dept. de Psychiatrie (Switzerland)

    2005-04-15

    Idiopathic Parkinson's disease (PD) and Alzheimer's disease (AD) are the main neuro-degenerative diseases (NDDs) seen clinically. They share some common clinical symptoms and neuro-pathological findings. The increase of life expectancy in the developed countries will inevitably contribute to enhance the prevalence of these diseases. Behavioral disorders, common in NDDs, will produce major care management challenges. Idiopathic Parkinson's disease corresponds to a histopathological diagnosis, based on the observation of a de-pigmentation and a neuronal loss in the substantia nigra, as well as on the presence of intra-neuronal inclusion bodies. AD is insidious with slowly progressive dementia in which the decline in memory constitutes the main complaint. The diagnosis of definite AD requires the presence of clinical criteria as well as the histopathological confirmation of brain lesions. The two main lesions are the presence of senile plaques and neuro-fibrillary tangles. Positron emission tomography (PET) explores cerebral metabolism and neurotransmitter kinetics in NDDs using principally [{sup 18}F]-deoxyglucose and [{sup 18}F]-dopa. Nigrostriatal dopaminergic function is altered in PD, as evidenced by the low uptake of [{sup 18}F]-dopa in the posterior putamen as compared to anterior putamen and caudate nucleus. In contrast, [{sup 18}F]-dopa uptake is equally depressed in all striatal structures in progressive supra-nuclear palsy. Regional glucose metabolism at rest is preserved in elderly once cerebral atrophy is taken into account. On the contrary, glucose metabolism is globally reduced in AD, with marked decrease in the parietal and temporal regions. PET has proved to be useful to study in vivo neurochemical processes in patients suffering from NDDs. The potential of this approach is still largely unexploited, and depends on new ligand production to establish early diagnosis and treatment follow-up. (author)

  20. Are viruses associated with human breast cancer? Scrutinizing the molecular evidence.

    Science.gov (United States)

    Joshi, Deepti; Buehring, Gertrude Case

    2012-08-01

    The three viruses most studied as possible causes of human breast cancer are mouse mammary tumor virus-like sequences (MMTV-LS), Epstein-Barr virus (EBV), and oncogenic (high risk) types of human papilloma virus (HPV). The first step in fulfilling traditional criteria for inferring that a cancer is caused by a virus is to demonstrate the virus in the affected tissue. Molecular techniques, compared to host antibody assessment and immunohistochemistry, are the most definitive in establishing viral presence. Results of 85 original molecular research investigations to detect one or more of the three viruses have been extremely divergent with no consensus reached. We evaluated the methodology of these studies for the following: type of molecular assay, DNA/RNA quality control, positive and negative assay controls, type of fixation, genome targets, methods for preventing and detecting molecular contamination, pathology of specimens processed, sample size, and proportion of specimens positive for the viral genome region targeted. Only seven of the studies convincingly demonstrated the presence of an oncogenic virus biomarker (EBV: 4/30 studies (13%); HPV 3/29 studies (10%), whereas 25 convincingly demonstrated absence of the virus studied (MMTV-LS: 4/25 (16%); EBV: 15/30 (50%); 6/29 (21%). The remainder of the studies suffered shortcomings, which, in our opinion, prevented a definitive conclusion. Only one of the studies compared frequency of the virus in breast tissue of breast cancer patients versus appropriate normal control subjects with no history of breast cancer. None of the studies were designed as epidemiologic studies to determine if the presence of the virus was significantly associated with breast cancer. Based on our evaluation, the data in the publications reviewed here remain preliminary, and do not justify a conclusion that MMTV-LS, HPV, or EBV are causally associated with breast cancer. However, they form a valuable basis for redirecting future studies.

  1. Molecular characterization of human calicivirus associated with acute diarrheal disease in mexican children

    Directory of Open Access Journals (Sweden)

    Gómez-Santiago Fabián

    2012-02-01

    Full Text Available Abstract Background Human caliciviruses (HuCV are emerging enteric pathogens that are a common cause of diarrhea in humans worldwide. Due to the paucity of information on the molecular characterization of HuCV circulating in Mexico, the aim of this work was to investigate the diversity and molecular epidemiology of the HuCV infection associated with acute diarrheal disease in Mexican children aged up to 5 years. Results Of the 131/414 (32% HuCV positive-specimens analyzed, 128 were identified as Norovirus (NoV and three as Sapovirus (SaV. Of the NoV positive specimens, 118/128 (92% were NoV GII and 10/128(8% were untypeable by RT-PCR in both polymerase and capsid genes, whereas one SaV isolate was further confirmed by sequencing as GI.2. Phylogenetic analysis based on polymerase partial gene sequences from 89/131 (68% HuCV isolates showed that 86/89 (97% belong to NoV GII.4 with three main variant clusters of this genotype, 2/89 (2% to NoV GII.2, and 1/89 (1% to SaV GI.2. Furthermore, partial sequencing of the capsid gene VP1 of 63/131 (48% strains indicated that 61/63 (97% correlated with NoV GII.4, whereas only 2/63 (3% clustered to NoV GII.2. HuCV infections were detected throughout the year, and the highest number of cases positive for NoV was found in children between 7 and 18 months of age (60%. Conclusions This study highlights the usefulness of analyzing both polymerase and capsid genes for molecular characterization of HuCV and demonstrates the relatedness and predominance of NoV GII.4 with acute diarrheal disease in young Mexican children, thus contributing to better understanding of the molecular epidemiology of this disease.

  2. Molecular Epidemiological and Antibiotic Susceptibility Characterization of Brucella Isolates from Humans in Sicily, Italy▿

    Science.gov (United States)

    Marianelli, Cinzia; Graziani, Caterina; Santangelo, Carmela; Xibilia, Maria Teresa; Imbriani, Alida; Amato, Rosa; Neri, Domenico; Cuccia, Mario; Rinnone, Sebastiano; Di Marco, Vincenzo; Ciuchini, Franco

    2007-01-01

    Brucellosis is a serious problem in Sicily. Brucella melitensis was identified as the species most frequently isolated in humans in Italy. No data, however, are available about the molecular epidemiological characterization of Brucella isolates from humans. We have conducted this study to molecularly characterize clinical isolates of Brucella spp. and to evaluate their antimicrobial susceptibilities. Twenty Brucella isolates were studied. Differential growth characteristics and DNA polymorphisms such as the restriction patterns of the PCR-amplified omp2a and omp2b genes, rpoB nucleotide sequencing, and multiple-locus variable-number tandem repeat analysis of 16 loci (MLVA-16) were used to characterize the strains. In vitro antibiotic susceptibility was determined by the E-test method on two different agar media, and the results were compared. All isolates were identified as B. melitensis biovar 3. rpoB nucleotide sequence analysis allowed the identification of two different genotypes of B. melitensis biovar 3. On the other hand, the MLVA-16 typing assay recognized 17 distinct genotypes. All isolates were sensitive to all tested antibiotics (rifampin, doxycycline, ciprofloxacin, ceftriaxone, and trimethoprim-sulfamethoxazole), and the Mueller-Hinton agar plate is recommended for antibiotic susceptibility testing by the E-test method. Our findings identify B. melitensis biovar 3 as the etiological agent isolated in Sicily and encourage the use of both molecular methods, and in particular of the MLVA-16 assay, in epidemiological trace-back analysis. This study represents the first epidemiological data from molecular typing of Brucella strains circulating in Italy and, in particular, in eastern Sicily. PMID:17634297

  3. Molecular characterization of Cryptosporidium parvum isolates from human cryptosporidiosis cases in Scotland.

    Science.gov (United States)

    Deshpande, A P; Jones, B L; Connelly, L; Pollock, K G; Brownlie, S; Alexander, C L

    2015-02-01

    Cryptosporidium parvum (C. parvum) is one of the most prevalent protozoan pathogens responsible for inducing human and animal disease worldwide. In this study, the glycoprotein-60 (gp60) subtyping tool was employed to assess the molecular diversity of C. parvum from human feces throughout Scotland during potential outbreaks. Over a 24-month period, microscopy analysis revealed 1139 positive feces containing Cryptosporidium species with 256 identified by molecular methods specifically as C. parvum. Cryptosporidium parvum was shown to be more prevalent in rural areas of Scotland and subtyping of 87 isolates demonstrated the predominant family as IIa, which occurred in 94% (n=82) of isolates. The IIaA15G1R1 subtype was most common, being isolated from 47% (n=41) of Scottish human cases. Non-IIa strains constituted a total of 5 isolates and included subtypes from the IIc, IId and IIg families. This information contributes significantly to existing knowledge and understanding of C. parvum subtypes in Scotland which is vital in assisting with the management of future local and national outbreaks.

  4. Molecular Imaging of Human Embryonic Stem Cells Stably Expressing Human PET Reporter Genes After Zinc Finger Nuclease-Mediated Genome Editing.

    Science.gov (United States)

    Wolfs, Esther; Holvoet, Bryan; Ordovas, Laura; Breuls, Natacha; Helsen, Nicky; Schönberger, Matthias; Raitano, Susanna; Struys, Tom; Vanbilloen, Bert; Casteels, Cindy; Sampaolesi, Maurilio; Van Laere, Koen; Lambrichts, Ivo; Verfaillie, Catherine M; Deroose, Christophe M

    2017-10-01

    Molecular imaging is indispensable for determining the fate and persistence of engrafted stem cells. Standard strategies for transgene induction involve the use of viral vectors prone to silencing and insertional mutagenesis or the use of nonhuman genes. Methods: We used zinc finger nucleases to induce stable expression of human imaging reporter genes into the safe-harbor locus adeno-associated virus integration site 1 in human embryonic stem cells. Plasmids were generated carrying reporter genes for fluorescence, bioluminescence imaging, and human PET reporter genes. Results: In vitro assays confirmed their functionality, and embryonic stem cells retained differentiation capacity. Teratoma formation assays were performed, and tumors were imaged over time with PET and bioluminescence imaging. Conclusion: This study demonstrates the application of genome editing for targeted integration of human imaging reporter genes in human embryonic stem cells for long-term molecular imaging. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  5. Effects of phenylpropanolamine (PPA) on in vitro human erythrocyte membranes and molecular models.

    Science.gov (United States)

    Suwalsky, Mario; Zambrano, Pablo; Mennickent, Sigrid; Villena, Fernando; Sotomayor, Carlos P; Aguilar, Luis F; Bolognin, Silvia

    2011-03-18

    Norephedrine, also called phenylpropanolamine (PPA), is a synthetic form of the ephedrine alkaloid. After reports of the occurrence of intracranial hemorrhage and other adverse effects, including several deaths, PPA is no longer sold in USA and Canada. Despite the extensive information about PPA toxicity, reports on its effects on cell membranes are scarce. With the aim to better understand the molecular mechanisms of the interaction of PPA with cell membranes, ranges of concentrations were incubated with intact human erythrocytes, isolated unsealed human erythrocyte membranes (IUM), and molecular models of cell membranes. The latter consisted in bilayers built-up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), phospholipid classes present in the outer and inner monolayers of most plasmatic cell membranes, respectively. The capacity of PPA to perturb the bilayer structures of DMPC and DMPE was assessed by X-ray diffraction, DMPC large unilamellar vesicles (LUV) and IUM were studied by fluorescence spectroscopy, and intact human erythrocytes were observed by scanning electron microscopy (SEM). This study presents evidence that PPA affects human red cell membranes as follows: (a) in SEM studies on human erythrocytes it was observed that 0.5 mM PPA induced shape changes; (b) in IUM PPA induced a sharp decrease in the fluorescence anisotropy in the lipid bilayer acyl chains in a concentration range lower than 100 μM; (c) X-ray diffraction studies showed that PPA in the 0.1-0.5 mM range induced increasing structural perturbation to DMPC, but no effects on DMPE multibilayers were detected. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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. Microphthalmia-associated transcription factor as the molecular target of cadmium toxicity in human melanocytes

    Energy Technology Data Exchange (ETDEWEB)

    Chantarawong, Wipa [Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai (Japan); Inter Departmental Multidisciplinary Graduate Program in Bioscience, Faculty of Science, Kasetsart University, Bangkok (Thailand); Takeda, Kazuhisa; Sangartit, Weerapon; Yoshizawa, Miki [Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai (Japan); Pradermwong, Kantimanee [Department of Zoology, Faculty of Science, Kasetsart University, Bangkok (Thailand); Shibahara, Shigeki, E-mail: shibahar@med.tohoku.ac.jp [Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai (Japan)

    2014-11-28

    Highlights: • In human melanocytes, cadmium decreases the expression of MITF-M and tyrosinase and their mRNAs. • In human melanoma cells, cadmium decreases the expression of MITF-M protein and tyrosinase mRNA. • Expression of MITF-H is less sensitive to cadmium toxicity in melanocyte-linage cells. • Cadmium does not decrease the expression of MITF-H in retinal pigment epithelial cells. • MITF-M is the molecular target of cadmium toxicity in melanocytes. - Abstract: Dietary intake of cadmium is inevitable, causing age-related increase in cadmium accumulation in many organs, including hair, choroid and retinal pigment epithelium (RPE). Cadmium has been implicated in the pathogenesis of hearing loss and macular degeneration. The functions of cochlea and retina are maintained by melanocytes and RPE, respectively, and the differentiation of these pigment cells is regulated by microphthalmia-associated transcription factor (MITF). In the present study, we explored the potential toxicity of cadmium in the cochlea and retina by using cultured human melanocytes and human RPE cell lines. MITF consists of multiple isoforms, including melanocyte-specific MITF-M and widely expressed MITF-H. Levels of MITF-M protein and its mRNA in human epidermal melanocytes and HMV-II melanoma cells were decreased significantly by cadmium. In parallel with the MITF reduction, mRNA levels of tyrosinase, the key enzyme of melanin biosynthesis that is regulated by MITF-M, were also decreased. In RPE cells, however, the levels of total MITF protein, constituting mainly MITF-H, were not decreased by cadmium. We thus identify MITF-M as the molecular target of cadmium toxicity in melanocytes, thereby accounting for the increased risk of disability from melanocyte malfunction, such as hearing and vision loss among people with elevated cadmium exposure.

  8. Management of neuro-oncologic emergencies.

    Science.gov (United States)

    Jo, J T; Schiff, D

    2017-01-01

    Patients with brain tumors and systemic malignancies are subject to diverse neurologic complications that require urgent evaluation and treatment. These neurologic conditions are commonly due to the tumor's direct effects on the nervous system, such as cerebral edema, increased intracranial pressure, seizures, spinal cord compression, and leptomeningeal metastases. In addition, neurologic complications can develop as a result of thrombocytopenia, coagulopathy, hyperviscosity syndromes, infection, immune-related disorders, and adverse effects of treatment. Patients may present with typical disease syndromes. However, it is not uncommon for patients to have more subtle, nonlocalizing manifestations, such as alteration of mental status, that could be attributed to other systemic, nonneurologic complications. Furthermore, neurologic complications are at times the initial manifestations of an undiagnosed malignancy. Therefore a high index of suspicion is essential for rapid assessment and management. Timely intervention may prolong survival and improve quality of life. In this chapter, we will discuss the common neuro-oncologic emergencies, including epidemiology, pathophysiology, clinical presentation, diagnosis, and treatment. © 2017 Elsevier B.V. All rights reserved.

  9. The Neuro-Ophthalmology of Mitochondrial Disease

    Science.gov (United States)

    Fraser, J. Alexander; Biousse, Valérie; Newman, Nancy J.

    2010-01-01

    Mitochondrial diseases frequently manifest neuro-ophthalmologic symptoms and signs. Because of the predilection of mitochondrial disorders to involve the optic nerves, extraocular muscles, retina, and even the retrochiasmal visual pathways, the ophthalmologist is often the first physician to be consulted. Disorders caused by mitochondrial dysfunction can result from abnormalities in either the mitochondrial DNA or in nuclear genes which encode mitochondrial proteins. Inheritance of these mutations will follow patterns specific to their somatic or mitochondrial genetics. Genotype-phenotype correlations are inconstant, and considerable overlap may occur among these syndromes. The diagnostic approach to the patient with suspected mitochondrial disease entails a detailed personal and family history, careful ophthalmic, neurologic, and systemic examination, directed investigations, and attention to potentially life-threatening sequelae. Although curative treatments for mitochondrial disorders are currently lacking, exciting research advances are being made, particularly in the area of gene therapy. Leber hereditary optic neuropathy, with its window of opportunity for timely intervention and its accessibility to directed therapy, offers a unique model to study future therapeutic interventions. Most patients and their relatives benefit from informed genetic counseling. PMID:20471050

  10. Bariatric Surgery and the Neuro-Ophthalmologist

    Science.gov (United States)

    Moss, Heather E.

    2016-01-01

    Background As the prevalence of obesity increases, so are the prevalences of weight related diseases and the incidence of surgical procedures to promote weight loss. It is important for neuro-ophthalmologists to be familiar with these procedures and possible downstream effects on afferent and efferent visual function. Evidence acquisition Review of ophthalmology, neurology, general surgery, obesity, endocrinology, nutrition, psychiatry and neurosurgery literature. Results Bariatric surgery is a safe and effective treatment for weight loss in obese individuals. There is level IV evidence that it is associated with improvement in idiopathic intracranial hypertension(IIH). Laboratory nutrient deficiencies are common following some types of bariatric procedures. Symptomatic deficiencies are less common but can be devastating. Thiamine deficiency can cause nystagmus and other symptoms in weeks to months following surgery, B12 or copper deficiency can cause optic neuropathy in the years to decades following bariatric surgery. Conclusions Bariatric surgery may be a treatment for IIH. Postoperative vitamin deficiencies may present with nystagmus, optic neuropathy, nyctalopia and/or ophthalmoparesis weeks to years after surgery. PMID:26764529

  11. [Neuro-rehabilitation for neurological disease].

    Science.gov (United States)

    Hara, Yukihiro

    2011-11-01

    Our understanding of motor learning, neuro-plasticity and functional recovery after the occurrence of brain lesion has grown significantly. New findings in basic neuroscience provided stimuli for research in motor rehabilitation. Electrical stimulation can be applied in a variety of ways to the neurological impairment. Especially, electromyography (EMG) initiated electrical muscle stimulation improves motor dysfunction of the hemiparetic arm and hand. Triggered electrical stimulation is reported to be more effective than non-triggered electrical stimulation in facilitating upper extremity motor recovery. Power-assisted FES induces greater muscle contraction by electrical stimulation in proportion to the voluntary integrated EMG signal picked up. Daily power-assisted FES home program therapy with the novel equipment has been able to improve wrist, finger extension and shoulder flexion effectively. Combined modulation of voluntary movement, proprioceptional sensory feedback and electrical stimulation might play an important role to facilitate impaired sensory-motor integration in power-assisted FES therapy. It is recognized that increased cerebral blood flow in the sensory-motor cortex area on the injured side during power-assisted FES session compared to simple active movement or simple electrical stimulation in a multi-channels Near-infrared spectroscopy (NIRS) study to non-invasively and dynamically measure hemoglobin levels in the brain during functional activity.

  12. Wave Forecasting Using Neuro Wavelet Technique

    Directory of Open Access Journals (Sweden)

    Pradnya Dixit

    2014-12-01

    Full Text Available In the present work a hybrid Neuro-Wavelet Technique is used for forecasting waves up to 6 hr, 12 hr, 18 hr and 24 hr in advance using hourly measured significant wave heights at an NDBC station 41004 near the east coast of USA. The NW Technique is employed by combining two methods, Discrete Wavelet Transform and Artificial Neural Networks. The hourly data of previously measured significant wave heights spanning over 2 years from 2010 and 2011 is used to calibrate and test the models. The discrete wavelet transform of NWT analyzes frequency of signal with respect to time at different scales. It decomposes time series into low (approximate and high (detail frequency components. The decomposition of approximate can be carried out up to desired multiple levels in order to provide more detail and approximate components which provides relatively smooth varying amplitude series. The neural network is trained with decorrelated approximate and detail wavelet coefficients. The outputs of networks during testing are reconstructed back using inverse DWT. The results were judged by drawing the wave plots, scatter plots and other error measures. The developed models show reasonable accuracy in prediction of significant wave heights from 6 to 24 hours. To compare the results traditional ANN models were also developed at the same location using the same data and for same time interval.

  13. [How xenon works: neuro and cardioprotection mechanisms].

    Science.gov (United States)

    Morais, Ricardo; Andrade, Luísa; Lourenço, André; Tavares, Jorge

    2014-01-01

    The Xenon, a noble gas, has anesthetics properties, associated with remarkable hemodynamic stability as well as cardioprotective, neuroprotective proprieties. Its physicochemical characteristics give him a quick induction and emergence of anesthesia, being free of deleterious effects in all organs and showing no teratogenicity. Such properties have led to a growing interest in improving the knowledge about this noble gas, in order to assess the mechanisms of neuro and cardioprotection induced and to assess the clinical indications for its use. Qualitative review of clinical trials on anesthesia with xenon. Studies were identified from MEDLINE and by hand-searching, using the following keywords: xenon, xenon anestesia, xenon neuroprotection, xenon cradioprotection. After several studies, including two randomized multicenter controlled trials, the use of xenon as an anesthetic in patients ASA I-II was approved in March 2007. However his use in clinical practice has been strongly limited by it's high price. It seems unlikely that the advantages it offers in relation to other anesthetics justify it's use in patients ASA I-II. Although, xenon may be a valuable asset in the reduction of co-morbilities and mortality in anesthesia of patients ASA III-IV, unfortunately, there are no large randomized control studies to prove it. Unfortunately, there are still no randomized or multicentric studies showing a favourable cost-benefit profile of xenon in ASA III-IV patients vs. other anaesthetics. The usefulness of xenon in Anesthesiology requires more studies to be defined.

  14. Bariatric Surgery and the Neuro-Ophthalmologist.

    Science.gov (United States)

    Moss, Heather E

    2016-03-01

    As the prevalence of obesity increases, so, too, do the prevalences of weight-related diseases and surgical procedures to promote weight loss. It is important for neuro-ophthalmologists to be familiar with these procedures and possible downstream effects on afferent and efferent visual function. Review of ophthalmology, neurology, general surgery, obesity, endocrinology, nutrition, psychiatry, and neurosurgery literature. Bariatric surgery is a safe and effective treatment for weight loss in obese individuals. There is Level IV evidence that it is associated with improvement in idiopathic intracranial hypertension (IIH). Laboratory nutrient deficiencies are common following some types of bariatric procedures. Symptomatic deficiencies are less common but can be devastating. Thiamine deficiency can cause nystagmus and other symptoms in weeks to months after surgery, whereas B12 or copper deficiency can cause optic neuropathy in years to decades following bariatric surgery. Bariatric surgery is a potential treatment for IIH. Postoperative vitamin deficiencies may cause nystagmus, optic neuropathy, nyctalopia, and/or ophthalmoparesis weeks to years after surgery.

  15. Displacement of Drugs from Human Serum Albumin: From Molecular Interactions to Clinical Significance.

    Science.gov (United States)

    Rimac, Hrvoje; Debeljak, Željko; Bojić, Mirza; Miller, Larisa

    2017-01-01

    Human serum albumin (HSA) is the most abundant protein in human serum. It has numerous functions, one of which is transport of small hydrophobic molecules, including drugs, toxins, nutrients, hormones and metabolites. HSA has the ability to interact with a wide variety of structurally different compounds. This promiscuous, nonspecific affinity can lead to sudden changes in concentrations caused by displacement, when two or more compounds compete for binding to the same molecular site. It is important to consider drug combinations and their binding to HSA when defining dosing regimens, as this can directly influence drug's free, active concentration in blood. In present paper we review drug interactions with potential for displacement from HSA, situations in which they are likely to occur and their clinical significance. We also offer guidelines in designing drugs with decreased binding to HSA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Molecular cytogenetics: making it safe for human embryonic stem cells to enter the clinic.

    Science.gov (United States)

    Josephson, Richard

    2007-07-01

    Regenerative therapies based on transplantation of cells derived from human embryonic stem cells (hESC) are currently being prepared for clinical trials. Unfortunately, recent evidence indicates that many kinds of changes can occur to hESC during expansion in culture, and alterations to the growth control mechanisms may be required to establish hESC lines at all. Changes in the genome and epigenome can affect the validity of in vitro and animal studies, and put transplant recipients at increased risk of cancer. New molecular cytogenetic technologies enable us to examine the whole human genome with ever-finer resolution. This review describes several techniques for whole-genome analysis and the information they can provide about hESC lines. Adoption of high-resolution genotyping into routine characterization may prevent highly discouraging clinical outcomes.

  17. Molecular diagnosis of Pseudoterranova decipiens s.s in human, France.

    Science.gov (United States)

    Brunet, Julie; Pesson, Bernard; Royant, Maude; Lemoine, Jean-Philippe; Pfaff, Alexander W; Abou-Bacar, Ahmed; Yera, Hélène; Fréalle, Emilie; Dupouy-Camet, Jean; Merino-Espinosa, Gema; Gómez-Mateos, Magdalena; Martin-Sanchez, Joaquina; Candolfi, Ermanno

    2017-06-06

    Anisakis and Pseudoterranova are the main genera involved in human infections caused by nematodes of the Anisakidae family. Species identification is complicated due to the lack of differential morphological characteristics at the larval stage, thus requiring molecular differentiation. Pseudoterranova larvae ingested through raw fish are spontaneously eliminated in most cases, but mechanical removal by means of endoscopy might be required. To date, only very few cases of Pseudoterranova infection have been reported in France. A 19-year-old woman from Northeastern France detected, while brushing her teeth, a larva exiting through her mouth. The patient who presented with headache, diarrhea, and abdominal cramps reported having eaten baked cod. The worm was a fourth-stage larva with a size of 22 × 0.9 mm, and molecular biology identified it as Pseudoterranova decipiens sensu stricto (s. s.). In a second P. decipiens infection case, occurring a few months later, a worm exited through the patient's nose after she had eaten raw sea bream. These two cases demonstrate that Pseudoterranova infection is not uncommon among French patients. Therefore, molecular techniques should be more widely applied for a better characterization of anisakidosis epidemiology in France.

  18. Molecular Epidemiology of Human Rhinoviruses and Enteroviruses Highlights Their Diversity in Sub-Saharan Africa.

    Science.gov (United States)

    L'Huillier, Arnaud G; Kaiser, Laurent; Petty, Tom J; Kilowoko, Mary; Kyungu, Esther; Hongoa, Philipina; Vieille, Gaël; Turin, Lara; Genton, Blaise; D'Acremont, Valérie; Tapparel, Caroline

    2015-12-08

    Human rhinoviruses (HRVs) and enteroviruses (HEVs) belong to the Enterovirus genus and are the most frequent cause of infection worldwide, but data on their molecular epidemiology in Africa are scarce. To understand HRV and HEV molecular epidemiology in this setting, we enrolled febrile pediatric patients participating in a large prospective cohort assessing the causes of fever in Tanzanian children. Naso/oropharyngeal swabs were systematically collected and tested by real-time RT-PCR for HRV and HEV. Viruses from positive samples were sequenced and phylogenetic analyses were then applied to highlight the HRV and HEV types as well as recombinant or divergent strains. Thirty-eight percent (378/1005) of the enrolled children harboured an HRV or HEV infection. Although some types were predominant, many distinct types were co-circulating, including a vaccinal poliovirus, HEV-A71 and HEV-D68. Three HRV-A recombinants were identified: HRV-A36/HRV-A67, HRV-A12/HRV-A67 and HRV-A96/HRV-A61. Four divergent HRV strains were also identified: one HRV-B strain and three HRV-C strains. This is the first prospective study focused on HRV and HEV molecular epidemiology in sub-Saharan Africa. This systematic and thorough large screening with careful clinical data management confirms the wide genomic diversity of these viruses, brings new insights about their evolution and provides data about associated symptoms.

  19. Binding of hydroxylated polybrominated diphenyl ethers with human serum albumin: Spectroscopic characterization and molecular modeling.

    Science.gov (United States)

    Yang, Lulu; Yang, Wu; Wu, Zhiwei; Yi, Zhongsheng

    2017-09-01

    Three hydroxylated polybrominated diphenyl ethers (OH-PBDEs), 3-OH-BDE-47, 5-OH-BDE-47, and 6-OH-BDE-47, were selected to investigate the interactions between OH-PBDEs with human serum albumin (HSA) under physiological conditions. The observed fluorescence quenching can be attributed to the formation of complexes between HSA and OH-PBDEs. The thermodynamic parameters at different temperatures indicate that the binding was caused by hydrophobic forces and hydrogen bonds. Molecular modeling and three-dimensional fluorescence spectrum showed conformational and microenvironmental changes in HSA. Circular dichroism analysis showed that the addition of OH-PBDEs changed the conformation of HSA with a minor reduction in α-helix content and increase in β-sheet content. Furthermore, binding distance r between the donor (HSA) and acceptor (three OH-PBDEs) calculated using Förster's nonradiative energy transfer theory was molecular dynamics simulations, the binding free energies (ΔGbind ) were calculated using molecular mechanics/Poisson - Boltzmann surface area method, and the crucial residues in HSA were identified. Copyright © 2017 John Wiley & Sons, Ltd.

  20. A novel gene signature for molecular diagnosis of human prostate cancer by RT-qPCR.

    Directory of Open Access Journals (Sweden)

    Federica Rizzi

    Full Text Available BACKGROUND: Prostate cancer (CaP is one of the most relevant causes of cancer death in Western Countries. Although detection of CaP at early curable stage is highly desirable, actual screening methods present limitations and new molecular approaches are needed. Gene expression analysis increases our knowledge about the biology of CaP and may render novel molecular tools, but the identification of accurate biomarkers for reliable molecular diagnosis is a real challenge. We describe here the diagnostic power of a novel 8-genes signature: ornithine decarboxylase (ODC, ornithine decarboxylase antizyme (OAZ, adenosylmethionine decarboxylase (AdoMetDC, spermidine/spermine N(1-acetyltransferase (SSAT, histone H3 (H3, growth arrest specific gene (GAS1, glyceraldehyde 3-phosphate dehydrogenase (GAPDH and Clusterin (CLU in tumour detection/classification of human CaP. METHODOLOGY/PRINCIPAL FINDINGS: The 8-gene signature was detected by retrotranscription real-time quantitative PCR (RT-qPCR in frozen prostate surgical specimens obtained from 41 patients diagnosed with CaP and recommended to undergo radical prostatectomy (RP. No therapy was given to patients at any time before RP. The bio-bank used for the study consisted of 66 specimens: 44 were benign-CaP paired from the same patient. Thirty-five were classified as benign and 31 as CaP after final pathological examination. Only molecular data were used for classification of specimens. The Nearest Neighbour (NN classifier was used in order to discriminate CaP from benign tissue. Validation of final results was obtained with 10-fold cross-validation procedure. CaP versus benign specimens were discriminated with (80+/-5% accuracy, (81+/-6% sensitivity and (78+/-7% specificity. The method also correctly classified 71% of patients with Gleason score or =7, an important predictor of final outcome. CONCLUSIONS/SIGNIFICANCE: The method showed high sensitivity in a collection of specimens in which a significant

  1. Cell Line Data Base: structure and recent improvements towards molecular authentication of human cell lines

    Science.gov (United States)

    Romano, Paolo; Manniello, Assunta; Aresu, Ottavia; Armento, Massimiliano; Cesaro, Michela; Parodi, Barbara

    2009-01-01

    The Cell Line Data Base (CLDB) is a well-known reference information source on human and animal cell lines including information on more than 6000 cell lines. Main biological features are coded according to controlled vocabularies derived from international lists and taxonomies. HyperCLDB (http://bioinformatics.istge.it/hypercldb/) is a hypertext version of CLDB that improves data accessibility by also allowing information retrieval through web spiders. Access to HyperCLDB is provided through indexes of biological characteristics and navigation in the hypertext is granted by many internal links. HyperCLDB also includes links to external resources. Recently, an interest was raised for a reference nomenclature for cell lines and CLDB was seen as an authoritative system. Furthermore, to overcome the cell line misidentification problem, molecular authentication methods, such as fingerprinting, single-locus short tandem repeat (STR) profile and single nucleotide polymorphisms validation, were proposed. Since this data is distributed, a reference portal on authentication of human cell lines is needed. We present here the architecture and contents of CLDB, its recent enhancements and perspectives. We also present a new related database, the Cell Line Integrated Molecular Authentication (CLIMA) database (http://bioinformatics.istge.it/clima/), that allows to link authentication data to actual cell lines. PMID:18927105

  2. Molecular basis of classic galactosemia from the structure of human galactose 1-phosphate uridylyltransferase.

    Science.gov (United States)

    McCorvie, Thomas J; Kopec, Jolanta; Pey, Angel L; Fitzpatrick, Fiona; Patel, Dipali; Chalk, Rod; Shrestha, Leela; Yue, Wyatt W

    2016-06-01

    Classic galactosemia is a potentially lethal disease caused by the dysfunction of galactose 1-phosphate uridylyltransferase (GALT). Over 300 disease-associated GALT mutations have been reported, with the majority being missense changes, although a better understanding of their underlying molecular effects has been hindered by the lack of structural information for the human enzyme. Here, we present the 1.9 Å resolution crystal structure of human GALT (hGALT) ternary complex, revealing a homodimer arrangement that contains a covalent uridylylated intermediate and glucose-1-phosphate in the active site, as well as a structural zinc-binding site, per monomer. hGALT reveals significant structural differences from bacterial GALT homologues in metal ligation and dimer interactions, and therefore is a zbetter model for understanding the molecular consequences of disease mutations. Both uridylylation and zinc binding influence the stability and aggregation tendency of hGALT. This has implications for disease-associated variants where p.Gln188Arg, the most commonly detected, increases the rate of aggregation in the absence of zinc likely due to its reduced ability to form the uridylylated intermediate. As such our structure serves as a template in the future design of pharmacological chaperone therapies and opens new concepts about the roles of metal binding and activity in protein misfolding by disease-associated mutants. © The Author 2016. Published by Oxford University Press.

  3. Molecular displacement of warfarin from human serum albumin by flavonoid aglycones

    Energy Technology Data Exchange (ETDEWEB)

    Poór, Miklós [Institute of Laboratory Medicine, University of Pécs, Pécs H-7624 (Hungary); Li, Yin; Kunsági-Máté, Sándor [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); János Szentágothai Research Center, H-7624 Pécs (Hungary); Petrik, József [Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, HR-10000 Zagreb (Croatia); Vladimir-Knežević, Sanda [Department of Pharmacognosy, Faculty of Pharmacy and Biochemistry, University of Zagreb, HR-10000 Zagreb (Croatia); Kőszegi, Tamás, E-mail: koszegit@freemail.hu [Institute of Laboratory Medicine, University of Pécs, Pécs H-7624 (Hungary)

    2013-10-15

    The well-known 4-hydroxycoumarin derivative warfarin is a widespread anticoagulant drug. Besides its strong albumin binding property warfarin has a narrow therapeutic window. Therefore, a few percent of displacement from albumin can result in serious biological consequences. The flavonoid molecular group also shows very strong plasma albumin binding characteristics occupying the same binding site. It is plausible to hypothesize that flavonoid aglycones may be able to displace warfarin from human serum albumin (HSA). In our study the competing activities of different flavone (acacetin, apigenin, chrysin, luteolin), flavonol (galangin, quercetin) and flavanone (hesperetin, naringenin) aglycones were investigated using fluorescence spectroscopy. Our results represent that flavonoids are able to displace warfarin from the surface of HSA. On the other hand, when comparing flavone or flavonol groups to flavanones the latter group seems to be much weaker competitor. These observations were also supported by calculation of stability constants. Our investigations strongly suggest that we should reckon with the described molecular displacement. However, further in vivo studies are needed to support the findings of our model system. -- Highlights: • Various flavonoids are able to displace warfarin from human serum albumin. • Flavones and flavonols are much more effective competitors than flavanones. • Even 300 nM aglycone concentrations show the interaction with 3 μM warfarin. • Flavonoid pairs show quasi-additive desorbing property. • Flavones and flavonols are much stronger competitors than the examined drugs.

  4. Molecular detection of cytomegalovirus, herpes simplex virus 2, human papillomavirus 16-18 in Turkish pregnants.

    Science.gov (United States)

    Dinc, Bedia; Bozdayi, Gulendam; Biri, Aydan; Kalkanci, Ayse; Dogan, Bora; Bozkurt, Nuray; Rota, Seyyal

    2010-01-01

    Human cytomegalovirus (CMV) is the most common cause of viral intrauterine infections in the world. Herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) are the main agents of viral sexually transmitted diseases, which cause genital ulcers and genital warts, respectively. HPV infection has been linked to the majority of the anogenital malignancies. The aim of this study was to detect the existence of CMV, HSV-2 and HPV type 16-18 in Turkish pregnants by using sensitive molecular assays. One hundred thirty-four women (18-41 years old; mean age ± SD: 27 ± 8) applied to outpatient clinic of Obstetrics and Gynecology, in between 18th - 22nd weeks of their pregnancy and a control group of 99 healthy women (15-39 years old; mean age ± SD: 24 ± 8) were included in the study. Cervical smear samples were used for DNA extraction. CMV, HSV-2 and HPV 16-18 detections were carried out by real time PCR and in house PCR method, respectively. Three patients (3/134; 2.2%) were found to be positive for each HPV and HSV-2. Dual infection with HPV and HSV was found in just one patient. HPV 18 was detected in all positive samples. CMV was found to be positive in two patients (2/134; 1.4 %). HPV, HSV and CMV must be screened due to high prevalence of these viruses in pregnants by using sensitive molecular methods.

  5. Molecular detection of cytomegalovirus, herpes simplex virus 2, human papillomavirus 16-18 in Turkish pregnants

    Directory of Open Access Journals (Sweden)

    Bedia Dinc

    Full Text Available OBJECTIVE: Human cytomegalovirus (CMV is the most common cause of viral intrauterine infections in the world. Herpes simplex virus type 2 (HSV-2 and human papillomavirus (HPV are the main agents of viral sexually transmitted diseases, which cause genital ulcers and genital warts, respectively. HPV infection has been linked to the majority of the anogenital malignancies. The aim of this study was to detect the existence of CMV, HSV-2 and HPV type 16-18 in Turkish pregnants by using sensitive molecular assays. METHODS: One hundred thirty-four women (18-41 years old; mean age ± SD: 27 ± 8 applied to outpatient clinic of Obstetrics and Gynecology, in between 18th - 22nd weeks of their pregnancy and a control group of 99 healthy women (15-39 years old; mean age ± SD: 24 ± 8 were included in the study. Cervical smear samples were used for DNA extraction. CMV, HSV-2 and HPV 16-18 detections were carried out by real time PCR and in house PCR method, respectively. RESULTS: Three patients (3/134; 2.2% were found to be positive for each HPV and HSV-2. Dual infection with HPV and HSV was found in just one patient. HPV 18 was detected in all positive samples. CMV was found to be positive in two patients (2/134; 1.4 %. CONCLUSION: HPV, HSV and CMV must be screened due to high prevalence of these viruses in pregnants by using sensitive molecular methods.

  6. Morphobiometrical and molecular study of two populations of Demodex folliculorum from humans.

    Science.gov (United States)

    de Rojas, Manuel; Riazzo, Cristina; Callejón, Rocío; Guevara, Diego; Cutillas, Cristina

    2012-01-01

    A morphobiometrical and molecular study of two populations of Demodex folliculorum from humans isolated from different habitats, skin and eyelashes follicles, were carried out. Morphological and biometrical studies revealed two closely related populations with any distinctive characteristics. For molecular study, a 436-bp region of the 16S rDNA gene and a 453-bp region of the cytochrome oxidase I (COI) gene from individual mites of each population considered were sequenced. Intraindividual and interindividual sequence variation was studied in both populations. Our data show that 16S rDNA is not a useful marker to discriminate between populations; however, COI gene sequences can help to identify the two populations considered, which are morphologically very close and difficult to separate by classic methods. These results are in agreement with the morphological and biometrical differences detected between D. folliculorum from eyelashes and human skin. This study appeals for the revision of the taxonomic status of the D. folliculorum populations, as well as for the species included within genus Demodex.

  7. Cell Line Data Base: structure and recent improvements towards molecular authentication of human cell lines.

    Science.gov (United States)

    Romano, Paolo; Manniello, Assunta; Aresu, Ottavia; Armento, Massimiliano; Cesaro, Michela; Parodi, Barbara

    2009-01-01

    The Cell Line Data Base (CLDB) is a well-known reference information source on human and animal cell lines including information on more than 6000 cell lines. Main biological features are coded according to controlled vocabularies derived from international lists and taxonomies. HyperCLDB (http://bioinformatics.istge.it/hypercldb/) is a hypertext version of CLDB that improves data accessibility by also allowing information retrieval through web spiders. Access to HyperCLDB is provided through indexes of biological characteristics and navigation in the hypertext is granted by many internal links. HyperCLDB also includes links to external resources. Recently, an interest was raised for a reference nomenclature for cell lines and CLDB was seen as an authoritative system. Furthermore, to overcome the cell line misidentification problem, molecular authentication methods, such as fingerprinting, single-locus short tandem repeat (STR) profile and single nucleotide polymorphisms validation, were proposed. Since this data is distributed, a reference portal on authentication of human cell lines is needed. We present here the architecture and contents of CLDB, its recent enhancements and perspectives. We also present a new related database, the Cell Line Integrated Molecular Authentication (CLIMA) database (http://bioinformatics.istge.it/clima/), that allows to link authentication data to actual cell lines.

  8. Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine

    Science.gov (United States)

    Pool, Martin; de Boer, H. Rudolf; Hooge, Marjolijn N. Lub-de; van Vugt, Marcel A.T.M.; de Vries, Elisabeth G.E.

    2017-01-01

    Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance. PMID:28638489

  9. Molecular Phylogenetics of Trichostrongylus Species (Nematoda: Trichostrongylidae) from Humans of Mazandaran Province, Iran.

    Science.gov (United States)

    Sharifdini, Meysam; Heidari, Zahra; Hesari, Zahra; Vatandoost, Sajad; Kia, Eshrat Beigom

    2017-06-01

    The present study was performed to analyze molecularly the phylogenetic positions of human-infecting Trichostrongylus species in Mazandaran Province, Iran, which is an endemic area for trichostrongyliasis. DNA from 7 Trichostrongylus infected stool samples were extracted by using in-house (IH) method. PCR amplification of ITS2-rDNA region was performed, and products were sequenced. Phylogenetic analysis of the nucleotide sequence data was performed using MEGA 5.0 software. Six out of 7 isolates had high similarity with Trichostrongylus colubriformis, while the other one showed high homology with Trichostrongylus axei registered in GenBank reference sequences. Intra-specific variations within isolates of T. colubriformis and T. axei amounted to 0-1.8% and 0-0.6%, respectively. Trichostrongylus species obtained in the present study were in a cluster with the relevant reference sequences from previous studies. BLAST analysis indicated that there was 100% homology among all 6 ITS2 sequences of T. colubriformis in the present study and most previously registered sequences of T. colubriformis from human, sheep, and goat isolates from Iran and also human isolates from Laos, Thailand, and France. The ITS2 sequence of T. axei exhibited 99.4% homology with the human isolate of T. axei from Thailand, sheep isolates from New Zealand and Iran, and cattle isolate from USA.

  10. A spectroscopic and molecular docking approach on the binding of tinzaparin sodium with human serum albumin

    Science.gov (United States)

    Abdullah, Saleh M. S.; Fatma, Sana; Rabbani, Gulam; Ashraf, Jalaluddin M.

    2017-01-01

    Protein bound toxins are poorly removed by conventional extracorporeal therapies. Venous thromboembolism (VTE) is a major cause of morbidity and mortality in patients with cancer. The interaction between tinzaparin, an inhibitor of angiotensin converting enzyme and human serum albumin, a principal plasma protein in the liver has been investigated in vitro under a simulated physiological condition by UV-vis spectrophotometry and fluorescence spectrometry. The intrinsic fluorescence intensity of human serum albumin was strongly quenched by tinzaparin (TP). The binding constants and binding stoichiometry can be calculated from the data obtained from fluorescence quenching experiments. The negative value of ΔG° reveals that the binding process is a spontaneous process. Thermodynamic analysis shows that the HSA-TP complex formation occurs via hydrogen bonds, hydrophobic interactions and undergoes slight structural changes as evident by far-UV CD. It indicated that the hydrophobic interactions play a main role in the binding of TP to human serum albumin. In addition, the distance between TP (acceptor) and tryptophan residues of human serum albumin (donor) was estimated to be 2.21 nm according to the Förster's resonance energy transfer theory. For the deeper understanding of the interaction, thermodynamic, and molecular docking studies were performed as well. Our docking results suggest that TP forms stable complex with HSA (Kb ∼ 104) and its primary binding site is located in subdomain IIA (Sudlow Site I). The results obtained herein will be of biological significance in pharmacology and clinical medicine.

  11. Molecular Characterization of Human Rotavirus from Children with Diarrhoeal Disease in Sokoto State, Nigeria

    Directory of Open Access Journals (Sweden)

    B. R. Alkali

    2016-01-01

    Full Text Available This study was conducted to detect and characterize prevalent human group A rotavirus strains from 200 diarrheic children in Sokoto, Nigeria, by ELISA, monoclonal antibody (Mab serotyping and Reverse Transcription-Polymerase Chain Reaction (RT-PCR techniques. Rotavirus was detected in 25.5% of the children. The G-serotypes observed in circulation were G4: 16 (59.3%, G1: 4 (14.8%, G2: 3 (11.1%, G3: 3 (11.1%, and G12: 1 (3.7%. The monoclonal antibody (Mab serotyping detected G1 and G3 but did not detect G4 and G2 serotypes. The Mab typing of the G1 and G3 serotypes was consistent with the result of the RT-PCR. The VP4 genotypes detected were P[6] 3 (13%, P[8] 11 (47.8%, and the rare human P genotype (P[9], found in 9 patients (39.1%. Nine strains identified with the common G and P combinations were G4 P[8] 5 (56%, G4 P[6] 1 (11%, G1 P[8] 2 (22%, and G3 P[8] 1 (11%, while seven strains with unusual combinations or rare G or P genotypes identified were G12 P[8] 1 (14%, G2 P[8] 2 (29%, and G4 P[9] 4 (57%. To our knowledge this is the first molecular study of human rotavirus and report of rare human G and P serotypes in Sokoto State.

  12. Cell and molecular biology of simian virus 40: implications for human infections and disease

    Science.gov (United States)

    Butel, J. S.; Lednicky, J. A.

    1999-01-01

    Simian virus 40 (SV40), a polyomavirus of rhesus macaque origin, was discovered in 1960 as a contaminant of polio vaccines that were distributed to millions of people from 1955 through early 1963. SV40 is a potent DNA tumor virus that induces tumors in rodents and transforms many types of cells in culture, including those of human origin. This virus has been a favored laboratory model for mechanistic studies of molecular processes in eukaryotic cells and of cellular transformation. The viral replication protein, named large T antigen (T-ag), is also the viral oncoprotein. There is a single serotype of SV40, but multiple strains of virus exist that are distinguishable by nucleotide differences in the regulatory region of the viral genome and in the part of the T-ag gene that encodes the protein's carboxyl terminus. Natural infections in monkeys by SV40 are usually benign but may become pathogenic in immunocompromised animals, and multiple tissues can be infected. SV40 can replicate in certain types of simian and human cells. SV40-neutralizing antibodies have been detected in individuals not exposed to contaminated polio vaccines. SV40 DNA has been identified in some normal human tissues, and there are accumulating reports of detection of SV40 DNA and/or T-ag in a variety of human tumors. This review presents aspects of replication and cell transformation by SV40 and considers their implications for human infections and disease pathogenesis by the virus. Critical assessment of virologic and epidemiologic data suggests a probable causative role for SV40 in certain human cancers, but additional studies are necessary to prove etiology.

  13. Ophthalmic and neuro-ophthalmic manifestations of sarcoidosis.

    Science.gov (United States)

    Kefella, Haben; Luther, Daniel; Hainline, Clotilde

    2017-11-01

    Sarcoidosis is a multisystemic inflammatory disease that commonly affects the eye and less often the neuro-ophthalmic pathways. The manifestations can be quite variable but can have characteristic signs and clinical features. This review provides a comprehensive overview of the various ocular and neuro-ophthalmic manifestations of sarcoidosis, emerging diagnostic measures and approach to treatment. Particular focus is given to recent advances in diagnostic approach and available treatment options. Laboratory investigations, chest and nuclear medicine imaging remain important techniques for helping to diagnose sarcoidosis. Recent evidence suggests a role for aqueous humor analysis in the diagnosis of ocular sarcoidosis. Characteristic neuroimaging may help differentiate neurosarcoidosis from other causes. The role of blind conjunctival biopsy for suspected neurosarcoidosis is discussed. The emerging role and use of biologics is delineated for the treatment of both ocular and neuro-ophthalmic sarcoidosis. Sarcoidosis can affect any part of the visual system: the most common ocular manifestation is uveitis and the most common neuro-ophthalmic manifestation is optic neuropathy. Although diagnosis remains challenging, recent advancements in diagnosis are promising. Emerging biologics with particular efficacy for ocular and neuro-ophthalmic disease provide expanding treatment options for sight-threatening disease.

  14. Seeded fibrillation as molecular basis of the species barrier in human prion diseases.

    Directory of Open Access Journals (Sweden)

    Lars Luers

    Full Text Available Prion diseases are transmissible spongiform encephalopathies in humans and animals, including scrapie in sheep, bovine spongiform encephalopathy (BSE in cattle, chronic wasting disease (CWD in deer, and Creutzfeldt-Jakob disease (CJD in humans. The hallmark of prion diseases is the conversion of the host-encoded prion protein (PrP(C to its pathological isoform PrP(Sc, which is accompanied by PrP fibrillation. Transmission is not restricted within one species, but can also occur between species. In some cases a species barrier can be observed that results in limited or unsuccessful transmission. The mechanism behind interspecies transmissibility or species barriers is not completely understood. To analyse this process at a molecular level, we previously established an in vitro fibrillation assay, in which recombinant PrP (recPrP as substrate can be specifically seeded by PrP(Sc as seed. Seeding with purified components, with no additional cellular components, is a direct consequence of the "prion-protein-only" hypothesis. We therefore hypothesise, that the species barrier is based on the interaction of PrP(C and PrP(Sc. Whereas in our earlier studies, the interspecies transmission in animal systems was analysed, the focus of this study lies on the transmission from animals to humans. We therefore combined seeds from species cattle, sheep and deer (BSE, scrapie, CWD with human recPrP. Homologous seeding served as a control. Our results are consistent with epidemiology, other in vitro aggregation studies, and bioassays investigating the transmission between humans, cattle, sheep, and deer. In contrast to CJD and BSE seeds, which show a seeding activity we can demonstrate a species barrier for seeds from scrapie and CWD in vitro. We could show that the seeding activity and therewith the molecular interaction of PrP as substrate and PrP(Sc as seed is sufficient to explain the phenomenon of species barriers. Therefore our data supports the hypothesis

  15. Protective effects of osmolytes in cryopreserving adherent neuroblastoma (Neuro-2a) cells.

    Science.gov (United States)

    Bailey, Trisha L; Wang, Mian; Solocinski, Jason; Nathan, Britto P; Chakraborty, Nilay; Menze, Michael A

    2015-12-01

    A simple method to cryopreserve adherent monolayers of neuronal cells is currently not available, but the development of this technique could facilitate numerous applications in the field of biomedical engineering, cell line development, and drug screening. However, complex tissues of some exceptional animals survive freezing in nature. These animals are known to accumulate several small molecular weight solutes prior to freezing. Following a similar strategy, we investigated the effects of osmolytes such as trehalose, proline, and sucrose as additives to the traditional cryoprotectant dimethyl sulfoxide (Me2SO) in modulating the cryopreservation outcome of mouse neuroblastoma (Neuro-2a) cells. Neuro-2a cells adhered to cell culture plates were incubated for 24 h at varying concentrations of trehalose, proline, sucrose and combinations of these compounds. Cells were cryopreserved for 24 h and cell viability post-freezing and thawing was quantified by trypan blue exclusion assay. On average, only 13.5% of adherent cells survived freezing in the presence of 10% Me2SO alone (control). Pre-incubation of cells with medium containing both trehalose and proline severely decreased cell proliferation, but increased cell recovery to about 53% of control. Furthermore, characterization using Raman microspectroscopy revealed that the addition of both trehalose and proline to 10% Me2SO substantially increased the size, and altered the nature, of ice crystals formed during freezing. Our results suggest that pre-incubation of Neuro-2a cells with trehalose and proline in combination provides cell protection along with alterations of ice structure in order to increase cell survival post-freezing. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Molecular Detection of Ancylostoma duodenale, Ancylostoma ceylanicum, and Necator americanus in Humans in Northeastern and Southern Thailand

    OpenAIRE

    Phosuk, Issarapong; Intapan, Pewpan M.; Thanchomnang, Tongjit; Sanpool, Oranuch; Janwan, Penchom; Laummaunwai, Porntip; Aamnart, Witthaya; Morakote, Nimit; Maleewong, Wanchai

    2013-01-01

    The 2 principal species of hookworms infecting humans are Necator americanus and Ancylostoma duodenale. Case studies on zoonotic hookworm infections with Ancylostoma ceylanicum and/or Ancylostoma caninum are known mainly from Asian countries. Of these 2 zoonotic species, only A. ceylanicum can develop to adulthood in humans. In the present study, we report a molecular-based survey of human hookworm infections present in southern and northeastern Thailand. Thirty larval hookworm samples were o...

  17. Evaluation and molecular characterization of human adenovirus in drinking water supplies: viral integrity and viability assays.

    Science.gov (United States)

    Fongaro, Gislaine; Nascimento, Mariana A do; Rigotto, Caroline; Ritterbusch, Giseli; da Silva, Alessandra D' A; Esteves, Paulo A; Barardi, Célia R M

    2013-05-28

    Human adenoviruses (HAdVs) are the second-leading cause of childhood gastroenteritis worldwide. This virus is commonly found in environmental waters and is very resistant to water disinfection and environmental stressors, especially UV light inactivation. Molecular techniques, such as PCR-based methods (Polymerase Chain Reaction), are commonly used to detect and identify viral contamination in water, although PCR alone does not allow the discrimination between infectious and non-infectious viral particles. A combination of cell culture and PCR has allowed detection of infectious viruses that grow slowly or fail to produce cytopathic effects (CPE) in cell culture. This study aimed to assess the integrity and viability of human adenovirus (HAdV) in environmental water and evaluate circulating strains by molecular characterization in three sites of the water supply in Florianópolis, Santa Catarina Island, Brazil: Peri Lagoon water, spring source water, and water from the public water supply system. Water samples were collected, concentrated and HAdV quantified by real-time PCR. Viral integrity was evaluated by enzymatic assay (DNase I) and infectivity by plaque assay (PA) and integrated cell culture using transcribed mRNA (ICC-RT-qPCR). Samples containing particles of infectious HAdV were selected for sequencing and molecular characterization. The analyzed sites contained 83, 66 and 58% undamaged HAdV particles (defined as those in which the genetic material is protected by the viral capsid) at Peri Lagoon, spring source water and public supply system water, respectively. Of these, 66% of the particles (by PA) and 75% (by ICC-RT-qPCR) HAdV were shown to be infectious, due to being undamaged in Peri Lagoon, 33% (by PA) and 58% (by ICC-RT-qPCR) in spring source water and 8% (by PA) and 25% (by ICC-RT-qPCR) in the public water supply system. ICC-RT-qPCR, a very sensitive and rapid technique, was able to detect as low as 1 × 102 HAdV genome copies per milliliter of

  18. Adaptive neuro-fuzzy controller of switched reluctance motor

    Directory of Open Access Journals (Sweden)

    Tahour Ahmed

    2007-01-01

    Full Text Available This paper presents an application of adaptive neuro-fuzzy (ANFIS control for switched reluctance motor (SRM speed. The ANFIS has the advantages of expert knowledge of the fuzzy inference system and the learning capability of neural networks. An adaptive neuro-fuzzy controller of the motor speed is then designed and simulated. Digital simulation results show that the designed ANFIS speed controller realizes a good dynamic behaviour of the motor, a perfect speed tracking with no overshoot and a good rejection of impact loads disturbance. The results of applying the adaptive neuro-fuzzy controller to a SRM give better performance and high robustness than those obtained by the application of a conventional controller (PI.

  19. 5th International Conference on Fuzzy and Neuro Computing

    CERN Document Server

    Panigrahi, Bijaya; Das, Swagatam; Suganthan, Ponnuthurai

    2015-01-01

    This proceedings bring together contributions from researchers from academia and industry to report the latest cutting edge research made in the areas of Fuzzy Computing, Neuro Computing and hybrid Neuro-Fuzzy Computing in the paradigm of Soft Computing. The FANCCO 2015 conference explored new application areas, design novel hybrid algorithms for solving different real world application problems. After a rigorous review of the 68 submissions from all over the world, the referees panel selected 27 papers to be presented at the Conference. The accepted papers have a good, balanced mix of theory and applications. The techniques ranged from fuzzy neural networks, decision trees, spiking neural networks, self organizing feature map, support vector regression, adaptive neuro fuzzy inference system, extreme learning machine, fuzzy multi criteria decision making, machine learning, web usage mining, Takagi-Sugeno Inference system, extended Kalman filter, Goedel type logic, fuzzy formal concept analysis, biclustering e...

  20. The Neuro-Complex: Some Comments and Convergences

    Directory of Open Access Journals (Sweden)

    Paul Martin

    2011-10-01

    Full Text Available In this short think-piece we trace the newly emerging and rapidly expanding dimensions and dynamics of the “neuro-complex.” What this amounts to, we suggest, are a series of bio or neuro “convergences” of sorts regarding the brain and mental worlds, which in turn are traceable through what we term the bio-psych, pharma-psych, subjectivity-selves, wellness-enhancement, and the neuroculture-neurofutures relational nexuses. These issues are then illustrated through two brief case studies regarding brain scanning technologies and the problems and prospects of cognitive enhancement. The paper concludes with some final reflections on these matters and a call for further research in this rich and challenging domain as the neuro-complex continues to expand in expected and unexpected, yet equally rich and fascinating, ways.

  1. Primary headache disorders and neuro-ophthalmologic manifestations

    Science.gov (United States)

    Schwartz, Daniel P; Robbins, Matthew S

    2012-01-01

    Headache is an extraordinarily common complaint presenting to medical practitioners in all arenas and specialties, particularly primary care physicians, neurologists, and ophthalmologists. A wide variety of headache disorders may manifest with a myriad of neuro-ophthalmologic symptoms, including orbital pain, disturbances of vision, aura, photophobia, lacrimation, conjunctival injection, ptosis, and other manifestations. The differential diagnosis in these patients is broad and includes both secondary, or symptomatic, and primary headache disorders. Awareness of the headache patterns and associated symptoms of these various disorders is essential to achieve the correct diagnosis. This paper reviews the primary headache disorders that prominently feature neuro-ophthalmologic manifestations, including migraine, the trigeminal autonomic cephalalgias, and hemicrania continua. Migraine variants with prominent neuro-ophthalmologic symptoms including aura without headache, basilar-type migraine, retinal migraine, and ophthalmoplegic migraine are also reviewed. This paper focuses particularly on the symptomatology of these primary headache disorders, but also discusses their epidemiology, clinical features, and treatment. PMID:28539781

  2. Surveillance of Canine Rabies in the Central African Republic: Impact on Human Health and Molecular Epidemiology.

    Science.gov (United States)

    Tricou, Vianney; Bouscaillou, Julie; Kamba Mebourou, Emmanuel; Koyanongo, Fidèle Dieudonné; Nakouné, Emmanuel; Kazanji, Mirdad

    2016-02-01

    Although rabies represents an important public health threat, it is still a neglected disease in Asia and Africa where it causes tens of thousands of deaths annually despite available human and animal vaccines. In the Central African Republic (CAR), an endemic country for rabies, this disease remains poorly investigated. To evaluate the extent of the threat that rabies poses in the CAR, we analyzed data for 2012 from the National Reference Laboratory for Rabies, where laboratory confirmation was performed by immunofluorescence and PCR for both animal and human suspected cases, and data from the only anti-rabies dispensary of the country and only place where post-exposure prophylaxis (PEP) is available. Both are located in Bangui, the capital of the CAR. For positive samples, a portion of the N gene was amplified and sequenced to determine the molecular epidemiology of circulating strains. In 2012, 966 exposed persons visited the anti-rabies dispensary and 632 received a post-exposure rabies vaccination. More than 90% of the exposed persons were from Bangui and its suburbs and almost 60% of them were under 15-years of age. No rabies-related human death was confirmed. Of the 82 samples from suspected rabid dogs tested, 69 were confirmed positive. Most of the rabid dogs were owned although unvaccinated. There was a strong spatiotemporal correlation within Bangui and within the country between reported human exposures and detection of rabid dogs (Prabies was endemic in the CAR in 2012 and had a detrimental impact on human health as shown by the hundreds of exposed persons who received PEP. Implementation of effective public health interventions including mass dog vaccination and improvement of the surveillance and the access to PEP are urgently needed in this country.

  3. Surveillance of Canine Rabies in the Central African Republic: Impact on Human Health and Molecular Epidemiology.

    Directory of Open Access Journals (Sweden)

    Vianney Tricou

    2016-02-01

    Full Text Available Although rabies represents an important public health threat, it is still a neglected disease in Asia and Africa where it causes tens of thousands of deaths annually despite available human and animal vaccines. In the Central African Republic (CAR, an endemic country for rabies, this disease remains poorly investigated.To evaluate the extent of the threat that rabies poses in the CAR, we analyzed data for 2012 from the National Reference Laboratory for Rabies, where laboratory confirmation was performed by immunofluorescence and PCR for both animal and human suspected cases, and data from the only anti-rabies dispensary of the country and only place where post-exposure prophylaxis (PEP is available. Both are located in Bangui, the capital of the CAR. For positive samples, a portion of the N gene was amplified and sequenced to determine the molecular epidemiology of circulating strains.In 2012, 966 exposed persons visited the anti-rabies dispensary and 632 received a post-exposure rabies vaccination. More than 90% of the exposed persons were from Bangui and its suburbs and almost 60% of them were under 15-years of age. No rabies-related human death was confirmed. Of the 82 samples from suspected rabid dogs tested, 69 were confirmed positive. Most of the rabid dogs were owned although unvaccinated. There was a strong spatiotemporal correlation within Bangui and within the country between reported human exposures and detection of rabid dogs (P<0.001. Phylogenetic analysis indicated that three variants belonging to Africa I and II lineages actively circulated in 2012.These data indicate that canine rabies was endemic in the CAR in 2012 and had a detrimental impact on human health as shown by the hundreds of exposed persons who received PEP. Implementation of effective public health interventions including mass dog vaccination and improvement of the surveillance and the access to PEP are urgently needed in this country.

  4. Molecular detection of eukaryotes in a single human stool sample from Senegal.

    Directory of Open Access Journals (Sweden)

    Ibrahim Hamad

    Full Text Available BACKGROUND: Microbial eukaryotes represent an important component of the human gut microbiome, with different beneficial or harmful roles; some species are commensal or mutualistic, whereas others are opportunistic or parasitic. The diversity of eukaryotes inhabiting humans remains relatively unexplored because of either the low abundance of these organisms in human gut or because they have received limited attention from a whole-community perspective. METHODOLOGY/PRINCIPAL FINDING: In this study, a single fecal sample from a healthy African male was studied using both culture-dependent methods and extended molecular methods targeting the 18S rRNA and ITS sequences. Our results revealed that very few fungi, including Candida spp., Galactomyces spp., and Trichosporon asahii, could be isolated using culture-based methods. In contrast, a relatively a high number of eukaryotic species could be identified in this fecal sample when culture-independent methods based on various primer sets were used. A total of 27 species from one sample were found among the 977 analyzed clones. The clone libraries were dominated by fungi (716 clones/977, 73.3%, corresponding to 16 different species. In addition, 187 sequences out of 977 (19.2% corresponded to 9 different species of plants; 59 sequences (6% belonged to other micro-eukaryotes in the gut, including Entamoeba hartmanni and Blastocystis sp; and only 15 clones/977 (1.5% were related to human 18S rRNA sequences. CONCLUSION: Our results revealed a complex eukaryotic community in the volunteer's gut, with fungi being the most abundant species in the stool sample. Larger investigations are needed to assess the generality of these results and to understand their roles in human health and disease.

  5. Molecular analyses of neurogenic defects in a human pluripotent stem cell model of fragile X syndrome.

    Science.gov (United States)

    Boland, Michael J; Nazor, Kristopher L; Tran, Ha T; Szücs, Attila; Lynch, Candace L; Paredes, Ryder; Tassone, Flora; Sanna, Pietro Paolo; Hagerman, Randi J; Loring, Jeanne F

    2017-03-01

    New research suggests that common pathways are altered in many neurodevelopmental disorders including autism spectrum disorder; however, little is known about early molecular events that contribute to the pathology of these diseases. The study of monogenic, neurodevelopmental disorders with a high incidence of autistic behaviours, such as fragile X syndrome, has the potential to identify genes and pathways that are dysregulated in autism spectrum disorder as well as fragile X syndrome. In vitro generation of human disease-relevant cell types provides the ability to investigate aspects of disease that are impossible to study in patients or animal models. Differentiation of human pluripotent stem cells recapitulates development of the neocortex, an area affected in both fragile X syndrome and autism spectrum disorder. We have generated induced human pluripotent stem cells from several individuals clinically diagnosed with fragile X syndrome and autism spectrum disorder. When differentiated to dorsal forebrain cell fates, our fragile X syndrome human pluripotent stem cell lines exhibited reproducible aberrant neurogenic phenotypes. Using global gene expression and DNA methylation profiling, we have analysed the early stages of neurogenesis in fragile X syndrome human pluripotent stem cells. We discovered aberrant DNA methylation patterns at specific genomic regions in fragile X syndrome cells, and identified dysregulated gene- and network-level correlates of fragile X syndrome that are associated with developmental signalling, cell migration, and neuronal maturation. Integration of our gene expression and epigenetic analysis identified altered epigenetic-mediated transcriptional regulation of a distinct set of genes in fragile X syndrome. These fragile X syndrome-aberrant networks are significantly enriched for genes associated with autism spectrum disorder, giving support to the idea that underlying similarities exist among these neurodevelopmental diseases. © The

  6. Molecular detection of eukaryotes in a single human stool sample from Senegal.

    Science.gov (United States)

    Hamad, Ibrahim; Sokhna, Cheikh; Raoult, Didier; Bittar, Fadi

    2012-01-01

    Microbial eukaryotes represent an important component of the human gut microbiome, with different beneficial or harmful roles; some species are commensal or mutualistic, whereas others are opportunistic or parasitic. The diversity of eukaryotes inhabiting humans remains relatively unexplored because of either the low abundance of these organisms in human gut or because they have received limited attention from a whole-community perspective. In this study, a single fecal sample from a healthy African male was studied using both culture-dependent methods and extended molecular methods targeting the 18S rRNA and ITS sequences. Our results revealed that very few fungi, including Candida spp., Galactomyces spp., and Trichosporon asahii, could be isolated using culture-based methods. In contrast, a relatively a high number of eukaryotic species could be identified in this fecal sample when culture-independent methods based on various primer sets were used. A total of 27 species from one sample were found among the 977 analyzed clones. The clone libraries were dominated by fungi (716 clones/977, 73.3%), corresponding to 16 different species. In addition, 187 sequences out of 977 (19.2%) corresponded to 9 different species of plants; 59 sequences (6%) belonged to other micro-eukaryotes in the gut, including Entamoeba hartmanni and Blastocystis sp; and only 15 clones/977 (1.5%) were related to human 18S rRNA sequences. Our results revealed a complex eukaryotic community in the volunteer's gut, with fungi being the most abundant species in the stool sample. Larger investigations are needed to assess the generality of these results and to understand their roles in human health and disease.

  7. Expression of Neuropeptide Y and Its Relationship with Molecular and Morphological Changes in Human Pituitary Adenomas.

    Science.gov (United States)

    Jia, Ruichao; Li, Mu; Chang, Binge; Chen, Laichao; Ma, Jingjian

    2015-12-01

    The purpose of this study was to explore the role of neuropeptide Y (NPY) on molecular and histological changes in human pituitary adenomas. The localization of NPY and its expression at the protein, messenger RNA (mRNA), and receptor levels were investigated here in different subcategories of pituitary adenomas. Immunohistochemical staining was performed in all cases to assess expression of NPY. Reverse transcription-polymerase chain reaction (RT-PCR) was used to study the mRNA expression of NPY. NPY subcellular localization was observed using immunoelectron microscopy in cytoplasm, rough endoplasmic reticulum, and cell matrix in four of the six cases of pituitary adenoma. NPY protein expression was observed in 59.6% of 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. mRNA expression of NPY was observed in all 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. Significantly different levels of expression were observed across different subcategories of pituitary adenoma. mRNA expression of Y1R and Y2R was observed across all subcategories of pituitary adenomas, and a positive correlation was observed between NPY and Y2R. In conclusion, evidence is provided here for the expression of NPY and its receptors, Y1R and Y2R, in human pituitary adenoma, and the levels of expression were found to differ across different subcategories. Differences in expression of Y2R in human pituitary adenomas were found to have remarkable statistical significance.

  8. Molecular analysis of formaldehyde-induced mutations in human lymphoblasts and E. coli

    Energy Technology Data Exchange (ETDEWEB)

    Crosby, R.M.; Richardson, K.K.; Craft, T.R.; Benforado, K.B.; Liber, H.L.; Skopek, T.R.

    1988-01-01

    The molecular nature of formaldehyde (HCHO)-induced mutations was studied in both human lymphoblasts and E. coli. Thirty HPRT/sup -/ human lymphoblast colonies induced by eight repetitive 150 ..mu..M HCHO treatments were characterized by Southern blot analysis. Fourteen of these mutants (47%) had visible deletions of some or all of the X-linked HPRT bands, indicating that HCHO can induce large losses of DNA in human lymphoblasts. In E. coli., DNA alterations induced by HCHO were characterized with use of the xanthine guanine phosphoribosyl transferase (gpt) gene as the genetic target. Exposure of E. coli to 4 mM HCHO for 1 hr induced large insertions (41%), large deletions (18%), and point mutations (41%). Dideoxy DNA sequencing revealed that most of the point mutations were transversions at GC base pairs. In contrast, exposure of E. coli to 40 mM HCHO for 1 hr produced 92% point mutations, 62% of which were transitions at a single AT base pair in the gene. Therefore, HCHO is capable of producing different genetic alterations in E. coli at different concentrations, suggesting fundamental differences in the mutagenic mechanisms operating at the two concentrations used. Naked pSV2gpt plasmid DNA was exposed to 3.3 or 10 mM HCHO and transformed into E. coli. Most of the resulting mutations were frameshifts, again suggesting a different mutagenic mechanism.

  9. Molecular Characterization of Salmonella from Human and Animal Origins in Uganda

    Directory of Open Access Journals (Sweden)

    Atek Atwiine Kagirita

    2017-01-01

    Full Text Available Sporadic Salmonella outbreaks with varying clinical presentations have been on the rise in various parts of Uganda. The sources of outbreaks and factors underlying the different clinical manifestation are curtailed by paucity of information on Salmonella genotypes and the associated virulence genes. This study reports molecular diversity of Salmonella enterica and their genetic virulence profiles among human and animal isolates. Characterization was done using Kauffman-White classification scheme and virulence genes analysis using multiplex PCR. Overall, 52% of the isolates belonged to serogroup D, 16% to serogroup E, 15% to poly F, H-S, and 12% to serogroup B. Serogroups A, C1, and C2 each consisted of only one isolate representing 5%. Virulence genes located on SPI-1 [spaN and sipB] and on SPI-2 [spiA] in addition to pagC and msgA were equally distributed in isolates obtained from all sources. Plasmid encoded virulence gene spvB was found in <5% of isolates from both human epidemic and animal origins whereas it occurred in 80% of clinical isolates. This study reveals that serogroup D is the predominant Salmonella serogroup in circulation and it is widely shared among animals and humans and calls for joint and coordinated surveillance for one health implementation in Uganda.

  10. Theranostic Properties of a Survivin-Directed Molecular Beacon in Human Melanoma Cells

    Science.gov (United States)

    Carpi, Sara; Fogli, Stefano; Giannetti, Ambra; Adinolfi, Barbara; Tombelli, Sara; Da Pozzo, Eleonora; Vanni, Alessia; Martinotti, Enrica; Martini, Claudia; Breschi, Maria Cristina; Pellegrino, Mario

    2014-01-01

    Survivin is an inhibitor of apoptosis overexpressed in different types of tumors and undetectable in most terminally differentiated normal tissues. In the current study, we sought to evaluate the in vitro theranostic properties of a molecular beacon-oligodeoxynucleotide (MB) that targets survivin mRNA. We used laser scanning confocal microscopy to study MB delivery in living cells and real-time PCR and western blot to assess selective survivin-targeting in human malignant melanoma cells. We further assess the pro-apoptotic effect of MB by measuring internucleosomal DNA fragmentation, dissipation of mitochondrial membrane potential (MMP) and changes in nuclear morphology. Transfection of MB into A375 and 501 Mel cells generated high signal intensity from the cytoplasm, while no signal was detected in the extracellular environment and in survivin-negative cells (i.e., human melanocytes and monocytes). MB time dependently decreased survivin mRNA and protein expression in melanoma cells with the maximum effect reached at 72 h. Treatment of melanoma cells with MB induced apoptosis by significant changes in MMP, accumulation of histone-complexed DNA fragments in the cytoplasm and nuclear condensation. MB also enhanced the pro-apoptotic effect of standard chemotherapeutic drugs tested at clinically relevant concentrations. The MB tested in the current study conjugates the ability of imaging with the pharmacological silencing activity against survivin mRNA in human melanoma cells and may represent an innovative approach for cancer diagnosis and treatment. PMID:25501971

  11. Methyl-triclosan binding to human serum albumin: multi-spectroscopic study and visualized molecular simulation.

    Science.gov (United States)

    Lv, Wenjuan; Chen, Yonglei; Li, Dayong; Chen, Xingguo; Leszczynski, Jerzy

    2013-10-01

    Methyl-triclosan (MTCS), a transformation product and metabolite of triclosan, has been widely spread in environment through the daily use of triclosan which is a commonly used anti-bacterial and anti-fungal substance in consumer products. Once entering human body, MTCS could affect the conformation of human serum albumin (HSA) by forming MTCS-HSA complex and alter function of protein and endocrine in human body. To evaluate the potential toxicity of MTCS, the binding mechanism of HSA with MTCS was investigated by UV-vis absorption, circular dichroism and Fourier transform infrared spectroscopy. Binding constants, thermodynamic parameters, the binding forces and the specific binding site were studied in detail. Binding constant at room tempreture (T = 298K) is 6.32 × 10(3)L mol(-1); ΔH(0), ΔS(0) and ΔG(0) were 22.48 kJ mol(-1), 148.16 J mol(-1)K(-1) and -21.68 kJ mol(-1), respectively. The results showed that the interactions between MTCS and HSA are mainly hydrophobic forces. The effects of MTCS on HSA conformation were also discussed. The binding distance (r = 1.2 nm) for MTCS-HSA system was calculated by the efficiency of fluorescence resonance energy transfer. The visualized binding details were also exhibited by molecular modeling method and the results could agree well with that from the experimental study. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Molecular Subtyping of PrPres in Human Sporadic CJD Brain Tissue.

    Science.gov (United States)

    Klug, G M; Lewis, V; Collins, S J

    2017-01-01

    Across the spectrum of sporadic human prion diseases (also known as transmissible spongiform encephalopathies: TSE), there is considerable phenotypic diversity. Cumulative scientific evidence supports that prions, the infectious agents of prion diseases, are constituted predominantly, if not exclusively, by misfolded, typically protease-resistant, disease-associated isoforms of the prion protein (PrPres). Consequently, tissue deposition of PrPres is considered a hallmark of prion disease pathology, and this can be visualized by Western blotting after tissue homogenization and treatment with proteinases, particularly proteinase K (PK). Indeed, Western blot profiles of PrPres are utilized as one marker of different prion strains, with such strains thought to contribute to at least part of the phenotypic variation observed in sporadic human prion disease. Typically, Western blotting of PrPres demonstrates three bands of different electrophoretic mobility, depicting the di-glycosylated, mono-glycosylated and unglycosylated species although further subclassification and the delineation of novel sporadic disease subtypes, such as variably protease-sensitive prionopathy, has contributed greater complexity. Nevertheless, it is the mobility of the unglycosylated PrPres band, the relative abundance of the two glycosylated bands or overall profile of the banding post-PK, in combination with the prion protein gene (PRNP) codon 129 genotype that allows the categorisation of molecular subtypes of sporadic human prion disease. These subtypes appear to correlate with distinct clinico-pathological profiles of sporadic Creutzfeldt-Jakob disease.

  13. Theranostic properties of a survivin-directed molecular beacon in human melanoma cells.

    Directory of Open Access Journals (Sweden)

    Sara Carpi

    Full Text Available Survivin is an inhibitor of apoptosis overexpressed in different types of tumors and undetectable in most terminally differentiated normal tissues. In the current study, we sought to evaluate the in vitro theranostic properties of a molecular beacon-oligodeoxynucleotide (MB that targets survivin mRNA. We used laser scanning confocal microscopy to study MB delivery in living cells and real-time PCR and western blot to assess selective survivin-targeting in human malignant melanoma cells. We further assess the pro-apoptotic effect of MB by measuring internucleosomal DNA fragmentation, dissipation of mitochondrial membrane potential (MMP and changes in nuclear morphology. Transfection of MB into A375 and 501 Mel cells generated high signal intensity from the cytoplasm, while no signal was detected in the extracellular environment and in survivin-negative cells (i.e., human melanocytes and monocytes. MB time dependently decreased survivin mRNA and protein expression in melanoma cells with the maximum effect reached at 72 h. Treatment of melanoma cells with MB induced apoptosis by significant changes in MMP, accumulation of histone-complexed DNA fragments in the cytoplasm and nuclear condensation. MB also enhanced the pro-apoptotic effect of standard chemotherapeutic drugs tested at clinically relevant concentrations. The MB tested in the current study conjugates the ability of imaging with the pharmacological silencing activity against survivin mRNA in human melanoma cells and may represent an innovative approach for cancer diagnosis and treatment.

  14. Neuro-Otological and Peripheral Nerve Involvement in Fabry Disease

    Science.gov (United States)

    Carmona, Sergio; Weinschelbaum, Romina; Pardal, Ana; Marchesoni, Cintia; Zuberbuhler, Paz; Acosta, Patricia; Cáceres, Guillermo; Kisinovsky, Isaac; Bayón, Luciana; Reisin, Ricardo

    2017-01-01

    Fabry disease (FD) is an X-linked lysosomal storage disease, with multisystemic glycosphingolipids deposits. Neuro-otological involvement leading to hearing loss and vestibular dysfunctions has been described, but there is limited information about the frequency, site of lesion, or the relationship with peripheral neuropathy. The aim was to evaluate the presence of auditory and vestibular symptoms, and assess neurophysiological involvement of the VIII cranial nerve, correlating these findings with clinical and neurophysiological features of peripheral neuropathy. We studied 36 patients with FD with a complete neurological and neuro-otological evaluation including nerve conduction studies, quantitative sensory testing (to evaluate small fiber by warm and cold threshold detection and cold and heat pain), vestibular evoked myogenic potentials, videonistagmography, audiometry and brainstem auditory evoked potentials. Neuro-otologic symptoms included hearing loss (22.2%), vertigo (27.8%) or both (25%). An involvement of either cochlear or vestibular function was identified in most patients (75%). In 70% of our patients the involvement of both cochlear and vestibular function could not be explained by a neural or vascular mechanism. Small fiber neuropathy was identified in 77.7%. There were no significant associations between neuro-otological and QST abnormalities. Neuro-otologic involvement is frequent and most likely under-recognized in patients with FD. It lacks a specific neural or vascular pattern, suggesting multi-systemic, end organ damage. Small fiber neuropathy is an earlier manifestation of FD, but there is no correlation between the development of neuropathy and neuro-otological abnormalities. PMID:28794847

  15. From emotions to consciousness – A neuro-phenomenal and neuro-relational approach

    Directory of Open Access Journals (Sweden)

    Georg eNorthoff

    2012-08-01

    Full Text Available The James-Lange theory considers emotional feelings as perceptions of physiological body changes. This approach has recently resurfaced and modified in both neuroscientific and philosophical concepts of embodiment of emotional feelings. In addition to the body, the role of the environment in emotional feeling needs to be considered. I here claim that the environment has not merely an indirect and instrumental i.e. modulatory role on emotional feelings via the body and its sensorimotor and vegetative functions. Instead, the environment may have a direct and non-instrumental, i.e., constitutional role in emotional feelings. This implies that the environment itself is constitutive of emotional feeling rather than the bodily representation of the environment. I call this the relational concept of emotional feeling. The present paper discusses recent data from neuroimaging that investigate emotions in relation to interoceptive processing and the brain’s intrinsic activity. These data show the intrinsic linkage of interoceptive stimulus processing to both exteroceptive stimuli and the brain’s intrinsic activity. This is possible only if the relation and thus the differences between intrinsic activity and intero- and exteroceptive stimuli is encoded into neural activity. Such relational coding makes possible the assignment of subjective and affective features to the otherwise objective and non-affective stimulus. I therefore consider emotions and thus emotional feeling to be intrinsically affective and subjective implying consciousness. The relational approach thus goes together with what may be described as neuro-phenomenal approach. Such neuro-phenomenal approach does not only inform emotions and emotional feeling but is also highly relevant to better understand the neuronal mechanisms underlying consciousness in general.

  16. PENERAPAN HIPNOTEACHING MELALUI NEURO-LINGUISTIC PROGRAMMING DALAM PEMBELAJARAN KIMIA

    Directory of Open Access Journals (Sweden)

    S. Ismuzaroh

    2013-10-01

    Full Text Available Tujuan penerapan hypnoteaching melalui neuro linguistic programming (NLP dalam proses pembelajaran kimia adalah untuk menghilangkan pikiran negatif siswa terhadap pembelajaran kimia, yang selanjutnya meningkatkan minat, motivasi dan keaktifan belajar kimia siswa. Hasil penelitian menunjukkan siswa lebih terbuka, berani mengemukakan pendapat terhadap permasalahan kimia yang pelajari, siswa merasa fresh, dan nyaman. Hypnoteaching goals through the application of neuro linguistic programming (NLP is a chemical in the learning process to eliminate the negative thoughts of students towards learning chemistry, which further increase the interest, motivation and active learning chemistry students. Results showed students were more open, daring to express opinions on issues studied chemistry, students feel fresh, and comfortable.

  17. Mathematical Modeling of Neuro-Vascular Coupling in Rat Cerebellum

    DEFF Research Database (Denmark)

    Rasmussen, Tina

    measured field potential is used as an indicator of neuronal activity, and the cortical blood flow is measured by means of laser-Doppler flowmetry. Using system identification methods, these measurements have been used to construct and validate parametric mathematical models of the neuro-vascular system....... Mathematical arguments as well as hypotheses about the physiological system have been used to construct the models.......Activity in the neurons called climbing fibers causes blood flow changes. But the physiological mechanisms which mediate the coupling are not well understood. This PhD thesis investigates the mechanisms of neuro-vascular coupling by means of mathematical methods. In experiments, the extracellularly...

  18. A Neuro-Control Design Based on Fuzzy Reinforcement Learning

    DEFF Research Database (Denmark)

    Katebi, S.D.; Blanke, M.

    This paper describes a neuro-control fuzzy critic design procedure based on reinforcement learning. An important component of the proposed intelligent control configuration is the fuzzy credit assignment unit which acts as a critic, and through fuzzy implications provides adjustment mechanisms...... ones instruct the neuro-control unit to adjust its weights and are simultaneously stored in the memory unit during the training phase. In response to the internal reinforcement signal (set point threshold deviation), the stored information is retrieved by the action applier unit and utilized for re...

  19. The HIV-1 transgenic rat model of neuroHIV

    OpenAIRE

    Vigorito, Michael; Connaghan, Kaitlyn P.; Chang, Sulie L.

    2015-01-01

    Despite the ability of current combination anti-retroviral therapy (cART) to limit the progression of HIV-1 to AIDS, HIV-positive individuals continue to experience neuroHIV in the form of HIV-associated neurological disorders (HAND), which can range from subtle to substantial neurocognitive impairment. NeuroHIV may also influence substance use, abuse, and dependence in HIV-positive individuals. Because of the nature of the virus, variables such as mental health co-morbidities make it difficu...

  20. Spectroscopy and molecular docking studies on the binding of propyl gallate to human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Guo-fei; Wang, Yu; Xi, Lei; Liu, Jin; Wang, Hao; Du, Lin-fang, E-mail: dulinfang@scu.edu.cn

    2015-03-15

    The interaction of propyl gallate (PG) with human serum albumin (HSA) was investigated by fluorescence, far-UV CD and FT-IR spectroscopic methods as well as molecular docking. Fluorescence emission spectra demonstrated that the HSA fluorescence was quenched by PG through static quenching and energy transfer with the binding constants in the order of 10{sup 5} L mol{sup −1}. The thermodynamic parameters (ΔH=−29.64 KJ mol{sup −1}, ΔS=2.7 J mol{sup −1} K{sup −1}) indicated that both hydrophobic force and hydrogen bond interactions played a leading role in the formation of PG–HSA complex. The results also showed the existence of a single binding site, which was located in subdomain IIA (site I) as revealed by molecular docking and competitive binding experiments. Molecular docking studies further showed the participation of several amino acids in PG–HSA complexation, which stabilized by H-bonding systems. The synchronous fluorescence spectra showed that the binding of drug caused the environment of tryptophan residues became more polar. FT-IR and CD spectroscopic further showed that drug complexation altered protein conformation by a major reduction of α-helix inducing a partial protein destabilization. - Highlights: • The interaction between propyl gallate and HSA has been investigated. • HSA fluorescence is quenched by propyl gallate through static quenching mechanism. • Both hydrophobic force and hydrogen bond play major role in the binding process. • Site I of the HSA is found to be the main binding site for propyl gallate. • The structure of HSA has been changed upon the interaction with propyl gallate.

  1. File list: ALL.Neu.20.AllAg.Neuro-2a [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.20.AllAg.Neuro-2a mm9 All antigens Neural Neuro-2a SRX814799,SRX367977,SRX3...X691794,SRX691798,SRX691797,SRX691795 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.20.AllAg.Neuro-2a.bed ...

  2. File list: ALL.Neu.05.AllAg.Neuro-2a [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.05.AllAg.Neuro-2a mm9 All antigens Neural Neuro-2a SRX367977,SRX814799,SRX3...X706576,SRX691799,SRX691797,SRX691795 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.05.AllAg.Neuro-2a.bed ...

  3. File list: Unc.Neu.20.AllAg.Neuro-2a [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.20.AllAg.Neuro-2a mm9 Unclassified Neural Neuro-2a SRX814799,SRX814802,SRX8...14803 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.20.AllAg.Neuro-2a.bed ...

  4. File list: Oth.Neu.50.AllAg.Neuro-2a [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.50.AllAg.Neuro-2a mm9 TFs and others Neural Neuro-2a SRX706575,SRX691800,SR...X691796,SRX706573,SRX691799,SRX691794,SRX691798,SRX691797,SRX691795 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.50.AllAg.Neuro-2a.bed ...

  5. Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance

    DEFF Research Database (Denmark)

    Alvero, Ayesha B; Chen, Rui; Fu, Han-Hsuan

    2009-01-01

    of the tumor and may be the primary source of recurrence. We describe the characterization of human ovarian cancer stem cells (OCSCs). These cells have a distinctive genetic profile that confers them with the capacity to recapitulate the original tumor, proliferate with chemotherapy, and promote recurrence...... to form spheroids in suspension, and the ability to recapitulate in vivo the original tumor. Chemotherapy eliminates the bulk of the tumor but it leaves a core of cancer cells with high capacity for repair and renewal. The molecular properties identified in these cells may explain some of the unique......A major burden in the treatment of ovarian cancer is the high percentage of recurrence and chemoresistance. Cancer stem cells (CSCs) provide a reservoir of cells that can self-renew, can maintain the tumor by generating differentiated cells [non-stem cells (non-CSCs)] which make up the bulk...

  6. Molecular effects of novel mutations in Hesx1/HESX1 associated with human pituitary disorders

    DEFF Research Database (Denmark)

    Brickman, J M; Clements, M; Tyrell, R

    2001-01-01

    resulting in a single amino acid substitution, Arg160Cys (R160C), is associated with a heritable form of the human condition of septo-optic dysplasia (SOD). We have examined the phenotype of affected members in this pedigree in more detail and demonstrate for the first time a genetic basis for midline...... defects associated with an undescended or ectopic posterior pituitary. A similar structural pituitary abnormality was observed in a second patient heterozygous for another mutation in HESX1, Ser170Leu (S170L). Association of S170L with a pituitary phenotype may be a direct consequence of the HESX1...... mutation since S170L is also associated with a dominant familial form of pituitary disease. However, a third mutation in HESX1, Asn125Ser (N125S), occurs at a high frequency in the Afro-Caribbean population and may therefore reflect a population-specific polymorphism. To investigate the molecular basis...

  7. The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes

    Directory of Open Access Journals (Sweden)

    Yuan Xie

    2015-10-01

    Full Text Available Glioblastoma (GBM is the most frequent and malignant form of primary brain tumor. GBM is essentially incurable and its resistance to therapy is attributed to a subpopulation of cells called glioma stem cells (GSCs. To meet the present shortage of relevant GBM cell (GC lines we developed a library of annotated and validated cell lines derived from surgical samples of GBM patients, maintained under conditions to preserve GSC characteristics. This collection, which we call the Human Glioblastoma Cell Culture (HGCC resource, consists of a biobank of 48 GC lines and an associated database containing high-resolution molecular data. We demonstrate that the HGCC lines are tumorigenic, harbor genomic lesions characteristic of GBMs, and represent all four transcriptional subtypes. The HGCC panel provides an open resource for in vitro and in vivo modeling of a large part of GBM diversity useful to both basic and translational GBM research.

  8. Discretization of Gene Expression Data Unmasks Molecular Subgroups Recurring in Different Human Cancer Types.

    Directory of Open Access Journals (Sweden)

    Manfred Beleut

    Full Text Available Despite the individually different molecular alterations in tumors, the malignancy associated biological traits are strikingly similar. Results of a previous study using renal cell carcinoma (RCC as a model pointed towards cancer-related features, which could be visualized as three groups by microarray based gene expression analysis. In this study, we used a mathematic model to verify the presence of these groups in RCC as well as in other cancer types. We developed an algorithm for gene-expression deviation profiling for analyzing gene expression data of a total of 8397 patients with 13 different cancer types and normal tissues. We revealed three common Cancer Transcriptomic Profiles (CTPs which recurred in all investigated tumors. Additionally, CTPs remained robust regardless of the functions or numbers of genes analyzed. CTPs may represent common genetic fingerprints, which potentially reflect the closely related biological traits of human cancers.

  9. Solid-state NMR, electrophysiology and molecular dynamics characterization of human VDAC2

    Energy Technology Data Exchange (ETDEWEB)

    Gattin, Zrinka; Schneider, Robert; Laukat, Yvonne; Giller, Karin [Max Planck Institute for Biophysical Chemistry (Germany); Maier, Elke [Theodor-Boveri-Institut (Biozentrum) der Universität Würzburg, Lehrstuhl für Biotechnologie (Germany); Zweckstetter, Markus; Griesinger, Christian [Max Planck Institute for Biophysical Chemistry (Germany); Benz, Roland [Theodor-Boveri-Institut (Biozentrum) der Universität Würzburg, Lehrstuhl für Biotechnologie (Germany); Becker, Stefan; Lange, Adam, E-mail: alange@fmp-berlin.de [Max Planck Institute for Biophysical Chemistry (Germany)

    2015-04-15

    The voltage-dependent anion channel (VDAC) is the most abundant protein of the outer mitochondrial membrane and constitutes the major pathway for the transport of ADP, ATP, and other metabolites. In this multidisciplinary study we combined solid-state NMR, electrophysiology, and molecular dynamics simulations, to study the structure of the human VDAC isoform 2 in a lipid bilayer environment. We find that the structure of hVDAC2 is similar to the structure of hVDAC1, in line with recent investigations on zfVDAC2. However, hVDAC2 appears to exhibit an increased conformational heterogeneity compared to hVDAC1 which is reflected in broader solid-state NMR spectra and less defined electrophysiological profiles.

  10. Crystal Structures of Human and Staphylococcus aureus Pyruvate Carboxylase and Molecular Insights into the Carboxyltransfer Reaction

    Energy Technology Data Exchange (ETDEWEB)

    Xiang,S.; Tong, L.

    2008-01-01

    Pyruvate carboxylase (PC) catalyzes the biotin-dependent production of oxaloacetate and has important roles in gluconeogenesis, lipogenesis, insulin secretion and other cellular processes. PC contains the biotin carboxylase (BC), carboxyltransferase (CT) and biotin-carboxyl carrier protein (BCCP) domains. We report here the crystal structures at 2.8-Angstroms resolution of full-length PC from Staphylococcus aureus and the C-terminal region (missing only the BC domain) of human PC. A conserved tetrameric association is observed for both enzymes, and our structural and mutagenesis studies reveal a previously uncharacterized domain, the PC tetramerization (PT) domain, which is important for oligomerization. A BCCP domain is located in the active site of the CT domain, providing the first molecular insights into how biotin participates in the carboxyltransfer reaction. There are dramatic differences in domain positions in the monomer and the organization of the tetramer between these enzymes and the PC from Rhizobium etli.

  11. Structures of Human Pumilio with Noncognate RNAs Reveal Molecular Mechanisms for Binding Promiscuity

    Energy Technology Data Exchange (ETDEWEB)

    Gupta,Y.; Nair, D.; Wharton, R.; Aggarwal, A.

    2008-01-01

    Pumilio is a founder member of the evolutionarily conserved Puf family of RNA-binding proteins that control a number of physiological processes in eukaryotes. A structure of human Pumilio (hPum) Puf domain bound to a Drosophila regulatory sequence showed that each Puf repeat recognizes a single nucleotide. Puf domains in general bind promiscuously to a large set of degenerate sequences, but the structural basis for this promiscuity has been unclear. Here, we describe the structures of hPum Puf domain complexed to two noncognate RNAs, CycBreverse and Puf5. In each complex, one of the nucleotides is ejected from the binding surface, in effect, acting as a 'spacer.' The complexes also reveal the plasticity of several Puf repeats, which recognize noncanonical nucleotides. Together, these complexes provide a molecular basis for recognition of degenerate binding sites, which significantly increases the number of mRNAs targeted for regulation by Puf proteins in vivo.

  12. Cell adhesion monitoring of human induced pluripotent stem cell based on intrinsic molecular charges

    Science.gov (United States)

    Sugimoto, Haruyo; Sakata, Toshiya

    2014-01-01

    We have shown a simple way for real-time, quantitative, non-invasive, and non-label monitoring of human induced pluripotent stem (iPS) cell adhesion by use of a biologically coupled-gate field effect transistor (bio-FET), which is based on detection of molecular charges at cell membrane. The electrical behavior revealed quantitatively the electrical contacts of integrin-receptor at the cell membrane with RGDS peptide immobilized at the gate sensing surface, because that binding site was based on cationic α chain of integrin. The platform based on the bio-FET would provide substantial information to evaluate cell/material bio-interface and elucidate biding mechanism of adhesion molecules, which could not be interpreted by microscopic observation.

  13. Elucidating Mechanisms of Molecular Recognition Between Human Argonaute and miRNA Using Computational Approaches

    KAUST Repository

    Jiang, Hanlun

    2016-12-06

    MicroRNA (miRNA) and Argonaute (AGO) protein together form the RNA-induced silencing complex (RISC) that plays an essential role in the regulation of gene expression. Elucidating the underlying mechanism of AGO-miRNA recognition is thus of great importance not only for the in-depth understanding of miRNA function but also for inspiring new drugs targeting miRNAs. In this chapter we introduce a combined computational approach of molecular dynamics (MD) simulations, Markov state models (MSMs), and protein-RNA docking to investigate AGO-miRNA recognition. Constructed from MD simulations, MSMs can elucidate the conformational dynamics of AGO at biologically relevant timescales. Protein-RNA docking can then efficiently identify the AGO conformations that are geometrically accessible to miRNA. Using our recent work on human AGO2 as an example, we explain the rationale and the workflow of our method in details. This combined approach holds great promise to complement experiments in unraveling the mechanisms of molecular recognition between large, flexible, and complex biomolecules.

  14. Molecular interaction and energy transfer between human serum albumin and bioactive component Aloe dihydrocoumarin

    Science.gov (United States)

    Zhang, Xiu-Feng; Xie, Ling; Liu, Yang; Xiang, Jun-Feng; Li, Lin; Tang, Ya-Lin

    2008-10-01

    Aloe dihydrocoumarin is an antioxidant and a candidate of immunomodulatory drug on the immune system and can balance physiological reactive oxygen species (ROS) levels which may be useful to maintain homeostasis. In order to explore the mechanism of drug action at a molecular level, the binding of Aloe dihydrocoumarin with human serum albumin (HSA) has been investigated by fluorescence, ultraviolet (UV), circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopy, fluorescence dynamics, and molecular dynamic docking for the first time. We observed a quenching of fluorescence of HSA in the presence of Aloe dihydrocoumarin and also analyzed the quenching results using the Stern-Volmer equation and obtained high affinity binding to HSA. A Förster type fluorescence resonance energy transfer mechanism is involved in this quenching of Trp fluorescence by Aloe dihydrocoumarin. From the CD and FT-IR results, it is apparent that the interaction of Aloe dihydrocoumarin with HSA causes a conformational change of the protein, with the loss of α-helix stability and the gain of β-sheet and β-turn content. Data obtained by fluorescence spectroscopy, fluorescence dynamics, CD, and FT-IR experiments along with the docking studies suggest that Aloe dihydrocoumarin binds to residues located in subdomain IIA of HSA.

  15. Spectroscopic and molecular modeling evidence of clozapine binding to human serum albumin at subdomain IIA

    Science.gov (United States)

    Wu, Xinhu; Liu, Jianjun; Wang, Qiang; Xue, Weiwei; Yao, Xiaojun; Zhang, Yan; Jin, Jing

    2011-09-01

    Various spectroscopy and molecular docking methods were used to examine the binding of Clozapine (CLZ) to human serum albumin (HSA) in this paper. By monitoring the intrinsic fluorescence of single Trp214 residue and performing Dansylamide (DNSA) displacement measurement, the specific binding of CLZ in the vicinity of Sudlow's Site I of HSA has been clarified. An apparent distance of 27.3 Å between the Trp214 and CLZ was obtained via fluorescence resonance energy transfer (FRET) method. In addition, the changes in the secondary structure of HSA after its complexation with CLZ ligand were studied with CD spectroscopy, which indicate that CLZ does not has remarkable effect on the structure of the protein. Moreover, thermal denaturation experiment shows that the HSA-CLZ complexes are conformationally more stable. Finally, the binding details between CLZ and HSA were further confirmed by molecular docking studies, which revealed that CLZ was bound at subdomain IIA through multiple interactions, such as hydrophobic effect, van der Waals forces and hydrogen bonding.

  16. Prevalence and Molecular Aspects of Human Hookworms in Guilan Province, Northern Iran

    Directory of Open Access Journals (Sweden)

    Meysam SHARIFDINI

    2017-09-01

    Full Text Available Background: Hookworm infection is one of the important Neglected Tropical Diseases (NTD in the world. It was previously more prevalent in the northern and southern parts of Iran with a prevalence rate higher than 40% in some endemic regions; nevertheless, the infection rate has decreased to less than 1%. This study aimed to determine prevalence and molecular aspects of hookworm infections in rural inhabitants of Fouman County, Guilan Province, northern IranMethods: This cross-sectional study was performed in 31 villages of Fouman district in Guilan Province, northern Iran during 2015-2016. Stool samples were collected from 1500 rural inhabitants and examined by formalin ethyl-acetate concentration as well as agar plate culture techniques. After treatment with albendazole, adult hookworms were isolated. FollowingDNA extraction,PCR amplification of ITS2-rDNA region was performed and the product was sequenced, followed by genetic variation analysis.Results: Of 1500 samples, one case was morphologically diagnosed as N. americanus. In addition, molecular characterization verified the presence of N. americanus, showing more than 95% similarity with sequences of N. americanus present in GenBank. The patient showed no clinical symptoms and a mild hypereosinophilia was the only laboratory finding observed. Conclusion: A reduced prevalence of human hookworms was demonstrated within Guilan Province located in north of Iran. The N. americanus originated from Guilan had  a high homology with the isolates found in Japan, Laos, Malaysia, and Australia.

  17. Acetaminophen interacts with human hemoglobin: optical, physical and molecular modeling studies.

    Science.gov (United States)

    Seal, Paromita; Sikdar, Jyotirmoy; Roy, Amartya; Haldar, Rajen

    2017-05-01

    Acetaminophen, a widely used analgesic and antipyretic drug has ample affinity to bind globular proteins. Here, we have illustrated a substantive study pertaining to the interaction of acetaminophen with human hemoglobin (HHb). Different spectroscopic (absorption, fluorescence, and circular dichroism (CD) spectroscopy), calorimetric, and molecular docking techniques have been employed in this study. Acetaminophen-induced graded alterations in absorbance and fluorescence of HHb confirm their interaction. Analysis of fluorescence quenching at different temperature and data obtained from isothermal titration calorimetry indicate that the interaction is static and the HHb has one binding site for the drug. The negative values of Gibbs energy change (ΔG0) and enthalpy changes (ΔH0) and positive value of entropy change (ΔS0) strongly suggest that it is entropy-driven spontaneous and exothermic reaction. The reaction involves hydrophobic pocket of the protein which is further stabilized by hydrogen bonding as evidenced from ANS and sucrose binding studies. These findings were also supported by molecular docking simulation study using AutoDock 4.2. The interaction influences structural integrity as well as functional properties of HHb as evidenced by CD spectroscopy, increased rate of co-oxidation and decreased esterase activity of HHb. So, from these findings, we may conclude that acetaminophen interacts with HHb through hydrophobic and hydrogen bonding, and the interaction perturbs the structural and functional properties of HHb.

  18. Caffeine and sulfadiazine interact differently with human serum albumin: A combined fluorescence and molecular docking study

    Science.gov (United States)

    Islam, Mullah Muhaiminul; Sonu, Vikash K.; Gashnga, Pynsakhiat Miki; Moyon, N. Shaemningwar; Mitra, Sivaprasad

    2016-01-01

    The interaction and binding behavior of the well-known drug sulfadiazine (SDZ) and psychoactive stimulant caffeine (CAF) with human serum albumin (HSA) was monitored by in vitro fluorescence titration and molecular docking calculations under physiological condition. The quenching of protein fluorescence on addition of CAF is due to the formation of protein-drug complex in the ground state; whereas in case of SDZ, the experimental results were explained on the basis of sphere of action model. Although both these compounds bind preferentially in Sudlow's site 1 of the protein, the association constant is approximately two fold higher in case of SDZ (∼4.0 × 104 M-1) in comparison with CAF (∼9.3 × 102 M-1) and correlates well with physico-chemical properties like pKa and lipophilicity of the drugs. Temperature dependent fluorescence study reveals that both SDZ and CAF bind spontaneously with HSA. However, the binding of SDZ with the protein is mainly governed by the hydrophobic forces in contrast with that of CAF; where, the interaction is best explained in terms of electrostatic mechanism. Molecular docking calculation predicts the binding of these drugs in different location of sub-domain IIA in the protein structure.

  19. Human Aquaporin-4 and Molecular Modeling: Historical Perspective and View to the Future

    Directory of Open Access Journals (Sweden)

    Giuseppe Felice Mangiatordi

    2016-07-01

    Full Text Available Among the different aquaporins (AQPs, human aquaporin-4 (hAQP4 has attracted the greatest interest in recent years as a new promising therapeutic target. Such a membrane protein is, in fact, involved in a multiple sclerosis-like immunopathology called Neuromyelitis Optica (NMO and in several disorders resulting from imbalanced water homeostasis such as deafness and cerebral edema. The gap of knowledge in its functioning and dynamics at the atomistic level of detail has hindered the development of rational strategies for designing hAQP4 modulators. The application, lately, of molecular modeling has proved able to fill this gap providing a breeding ground to rationally address compounds targeting hAQP4. In this review, we give an overview of the important advances obtained in this field through the application of Molecular Dynamics (MD and other complementary modeling techniques. The case studies presented herein are discussed with the aim of providing important clues for computational chemists and biophysicists interested in this field and looking for new challenges.

  20. Conformational relaxations of human serum albumin studied by molecular dynamics simulations with pressure jumps

    Directory of Open Access Journals (Sweden)

    Yesylevskyy S. O.

    2012-12-01

    Full Text Available Aim. In this work we developed a novel technique of obtaining the spectrum of conformational relaxations in a solvated protein using non-equilibrium molecular dynamics simulation. Methods. Structural relaxations in the protein are initiated by the abrupt jump of pressure in the NPT simulations. The change of the protein volume after the jump is monitored and the Maximum Entropy Method is used for spectral decomposition of the volume relaxation curve. The human serum albumin (HSA is used as a test case. Results. The obtained relaxation spectrum of HSA contains one component attributed to the bulk water and five components caused by the relaxations of the protein globule and its hydration shell. All relaxation components are in good agreement with the available experimental data obtained by the time-resolved spectroscopy and the broadband acoustic spectroscopy of HSA. Conclusions. The developed technique allows obtaining spectra of conformational relaxations of soluble proteins in a range of time scales from ~0.1 ps to ~50 ns utilizing single non-equilibrium molecular dynamics simulation.

  1. The Molecular and Cellular Effect of Homocysteine Metabolism Imbalance on Human Health

    Directory of Open Access Journals (Sweden)

    Henrieta Škovierová

    2016-10-01

    Full Text Available Homocysteine (Hcy is a sulfur-containing non-proteinogenic amino acid derived in methionine metabolism. The increased level of Hcy in plasma, hyperhomocysteinemia, is considered to be an independent risk factor for cardio and cerebrovascular diseases. However, it is still not clear if Hcy is a marker or a causative agent of diseases. More and more research data suggest that Hcy is an important indicator for overall health status. This review represents the current understanding of molecular mechanism of Hcy metabolism and its link to hyperhomocysteinemia-related pathologies in humans. The aberrant Hcy metabolism could lead to the redox imbalance and oxidative stress resulting in elevated protein, nucleic acid and carbohydrate oxidation and lipoperoxidation, products known to be involved in cytotoxicity. Additionally, we examine the role of Hcy in thiolation of proteins, which results in their molecular and functional modifications. We also highlight the relationship between the imbalance in Hcy metabolism and pathogenesis of diseases, such as cardiovascular diseases, neurological and psychiatric disorders, chronic kidney disease, bone tissue damages, gastrointestinal disorders, cancer, and congenital defects.

  2. Molecular Genetic Analysis of Human Endometrial Mesenchymal Stem Cells That Survived Sublethal Heat Shock

    Directory of Open Access Journals (Sweden)

    A. E. Vinogradov

    2017-01-01

    Full Text Available High temperature is a critical environmental and personal factor. Although heat shock is a well-studied biological phenomenon, hyperthermia response of stem cells is poorly understood. Previously, we demonstrated that sublethal heat shock induced premature senescence in human endometrial mesenchymal stem cells (eMSC. This study aimed to investigate the fate of eMSC-survived sublethal heat shock (SHS with special emphasis on their genetic stability and possible malignant transformation using methods of classic and molecular karyotyping, next-generation sequencing, and transcriptome functional analysis. G-banding revealed random chromosome breakages and aneuploidy in the SHS-treated eMSC. Molecular karyotyping found no genomic imbalance in these cells. Gene module and protein interaction network analysis of mRNA sequencing data showed that compared to untreated cells, SHS-survived progeny revealed some difference in gene expression. However, no hallmarks of cancer were found. Our data identified downregulation of oncogenic signaling, upregulation of tumor-suppressing and prosenescence signaling, induction of mismatch, and excision DNA repair. The common feature of heated eMSC is the silence of MYC, AKT1/PKB oncogenes, and hTERT telomerase. Overall, our data indicate that despite genetic instability, SHS-survived eMSC do not undergo transformation. After long-term cultivation, these cells like their unheated counterparts enter replicative senescence and die.

  3. New Insights into Molecular Organization of Human Neuraminidase-1: Transmembrane Topology and Dimerization Ability

    Science.gov (United States)

    Maurice, Pascal; Baud, Stéphanie; Bocharova, Olga V.; Bocharov, Eduard V.; Kuznetsov, Andrey S.; Kawecki, Charlotte; Bocquet, Olivier; Romier, Beatrice; Gorisse, Laetitia; Ghirardi, Maxime; Duca, Laurent; Blaise, Sébastien; Martiny, Laurent; Dauchez, Manuel; Efremov, Roman G.; Debelle, Laurent

    2016-12-01

    Neuraminidase 1 (NEU1) is a lysosomal sialidase catalyzing the removal of terminal sialic acids from sialyloconjugates. A plasma membrane-bound NEU1 modulating a plethora of receptors by desialylation, has been consistently documented from the last ten years. Despite a growing interest of the scientific community to NEU1, its membrane organization is not understood and current structural and biochemical data cannot account for such membrane localization. By combining molecular biology and biochemical analyses with structural biophysics and computational approaches, we identified here two regions in human NEU1 - segments 139-159 (TM1) and 316-333 (TM2) - as potential transmembrane (TM) domains. In membrane mimicking environments, the corresponding peptides form stable α-helices and TM2 is suited for self-association. This was confirmed with full-size NEU1 by co-immunoprecipitations from membrane preparations and split-ubiquitin yeast two hybrids. The TM2 region was shown to be critical for dimerization since introduction of point mutations within TM2 leads to disruption of NEU1 dimerization and decrease of sialidase activity in membrane. In conclusion, these results bring new insights in the molecular organization of membrane-bound NEU1 and demonstrate, for the first time, the presence of two potential TM domains that may anchor NEU1 in the membrane, control its dimerization and sialidase activity.

  4. The Transferrin Receptor: A Potential Molecular Imaging Marker for Human Cancer

    Directory of Open Access Journals (Sweden)

    Dagmar Högemann-Savellano

    2003-11-01

    Full Text Available Noninvasive imaging of differences between the molecular properties of cancer and normal tissue has the potential to enhance the detection of tumors. Because overexpression of endogenous transferrin receptor (TfR has been qualitatively described for various cancers and is presumably due to malignant transformation of cells, TfR may represent a suitable target for application of molecular imaging technologies to increase detection of smaller tumors. In the work reported here, investigation into the biology of this receptor using electron microscopy has demonstrated that iron oxide particles targeted to TfR are internalized and accumulate in lysosomal vesicles within cells. Biochemical analysis of the interaction of imaging probes with cells overexpressing the TfR demonstrated that the extent of accumulation, and therefore probe efficacy, is dependent on the nature of the chemical cross-link between transferrin and the iron oxide particle. These data were utilized to design and synthesize an improved imaging probe. Experiments demonstrate that the novel magnetic resonance imaging (MRI probe is sensitive enough to detect small differences in endogenous TfR expression in human cancer cell lines. Quantitative measurement of TfR overexpression in a panel of 27 human breast cancer patients demonstrated that 74% of patient cancer tissues overexpressed the TfR and that the sensitivity of the new imaging agent was suitable to detect TfR overexpression in greater than 40% of these cases. Based on a biochemical and cell biological approach, these studies have resulted in the synthesis and development of an improved MRI probe with the best in vitro and in vivo imaging properties reported to date.

  5. Molecular identification of nocardia isolates from clinical samples and an overview of human nocardiosis in Brazil.

    Directory of Open Access Journals (Sweden)

    Paulo Victor Pereira Baio

    Full Text Available BACKGROUND: Nocardia sp. causes a variety of clinical presentations. The incidence of nocardiosis varies geographically according to several factors, such as the prevalence of HIV infections, transplants, neoplastic and rheumatic diseases, as well as climate, socio-economic conditions and laboratory procedures for Nocardia detection and identification. In Brazil the paucity of clinical reports of Nocardia infections suggests that this genus may be underestimated as a cause of human diseases and/or either neglected or misidentified in laboratory specimens. Accurate identification of Nocardia species has become increasingly important for clinical and epidemiological investigations. In this study, seven clinical Nocardia isolates were identified by multilocus sequence analysis (MLSA and their antimicrobial susceptibility was also determined. Most Nocardia isolates were associated to pulmonary disease. METHODOLOGY/PRINCIPAL FINDINGS: The majority of Brazilian human isolates in cases reported in literature were identified as Nocardia sp. Molecular characterization was used for species identification of Nocardia nova, Nocardia cyriacigeorgica, Nocardia asiatica and Nocardia exalbida/gamkensis. Data indicated that molecular analysis provided a different Nocardia speciation than the initial biochemical identification for most Brazilian isolates. All Nocardia isolates showed susceptibility to trimethoprim-sulfamethoxazole, the antimicrobial of choice in the treatment nocardiosis. N. nova isolated from different clinical specimens from one patient showed identical antimicrobial susceptibility patterns and two distinct clones. CONCLUSIONS/SIGNIFICANCE: Although Brazil is the world's fifth-largest country in terms of land mass and population, pulmonary, extrapulmonary and systemic forms of nocardiosis were reported in only 6 of the 26 Brazilian states from 1970 to 2013. A least 33.8% of these 46 cases of nocardiosis proved fatal. Interestingly, coinfection

  6. Molecular identification of nocardia isolates from clinical samples and an overview of human nocardiosis in Brazil.

    Science.gov (United States)

    Baio, Paulo Victor Pereira; Ramos, Juliana Nunes; dos Santos, Louisy Sanches; Soriano, Morgana Fonseca; Ladeira, Elisa Martins; Souza, Mônica Cristina; Camello, Thereza Cristina Ferreira; Ribeiro, Marcio Garcia; Hirata Junior, Raphael; Vieira, Verônica Viana; Mattos-Guaraldi, Ana Luíza

    2013-01-01

    Nocardia sp. causes a variety of clinical presentations. The incidence of nocardiosis varies geographically according to several factors, such as the prevalence of HIV infections, transplants, neoplastic and rheumatic diseases, as well as climate, socio-economic conditions and laboratory procedures for Nocardia detection and identification. In Brazil the paucity of clinical reports of Nocardia infections suggests that this genus may be underestimated as a cause of human diseases and/or either neglected or misidentified in laboratory specimens. Accurate identification of Nocardia species has become increasingly important for clinical and epidemiological investigations. In this study, seven clinical Nocardia isolates were identified by multilocus sequence analysis (MLSA) and their antimicrobial susceptibility was also determined. Most Nocardia isolates were associated to pulmonary disease. The majority of Brazilian human isolates in cases reported in literature were identified as Nocardia sp. Molecular characterization was used for species identification of Nocardia nova, Nocardia cyriacigeorgica, Nocardia asiatica and Nocardia exalbida/gamkensis. Data indicated that molecular analysis provided a different Nocardia speciation than the initial biochemical identification for most Brazilian isolates. All Nocardia isolates showed susceptibility to trimethoprim-sulfamethoxazole, the antimicrobial of choice in the treatment nocardiosis. N. nova isolated from different clinical specimens from one patient showed identical antimicrobial susceptibility patterns and two distinct clones. Although Brazil is the world's fifth-largest country in terms of land mass and population, pulmonary, extrapulmonary and systemic forms of nocardiosis were reported in only 6 of the 26 Brazilian states from 1970 to 2013. A least 33.8% of these 46 cases of nocardiosis proved fatal. Interestingly, coinfection by two clones may occur in patients presenting nocardiosis. Nocardia infection may be

  7. The molecular and cellular basis of gonadal sex reversal in mice and humans.

    Science.gov (United States)

    Warr, Nick; Greenfield, Andy

    2012-01-01

    The mammalian gonad is adapted for the production of germ cells and is an endocrine gland that controls sexual maturation and fertility. Gonadal sex reversal, namely, the development of ovaries in an XY individual or testes in an XX, has fascinated biologists for decades. The phenomenon suggests the existence of genetic suppressors of the male and female developmental pathways and molecular genetic studies, particularly in the mouse, have revealed controlled antagonism at the core of mammalian sex determination. Both testis and ovary determination represent design solutions to a number of problems: how to generate cells with the right properties to populate the organ primordium; how to produce distinct organs from an initially bipotential primordium; how to pattern an organ when the expression of key cell fate determinants is initiated only in a discrete region of the primordium and extends to other regions asynchronously; how to coordinate the interaction between distinct cell types in time and space and stabilize the resulting morphology; and how to maintain the differentiated state of the organ throughout the adult period. Some of these, and related problems, are common to organogenesis in general; some are distinctive to gonad development. In this review, we discuss recent studies of the molecular and cellular events underlying testis and ovary development, with an emphasis on the phenomenon of gonadal sex reversal and its causes in mice and humans. Finally, we discuss sex-determining loci and disorders of sex development in humans and the future of research in this important area. Copyright © 2012 Wiley Periodicals, Inc.

  8. Neuro-immune interactions in inflammation and host defense: Implications for transplantation.

    Science.gov (United States)

    Chavan, Sangeeta S; Ma, Pingchuan; Chiu, Isaac M

    2017-09-23

    Sensory and autonomic neurons of the peripheral nervous system (PNS) play a critical role in regulating the immune system during tissue inflammation and host defense. Recent studies have identified the molecular mechanisms underlying the bidirectional communication between the nervous system and the immune system. Here, we highlight the studies that demonstrate the importance of the neuro-immune interactions in health and disease. Nociceptor sensory neurons detect immune mediators to produce pain, and release neuropeptides that act on the immune system to regulate inflammation. In parallel, neural reflex circuits including the vagus nerve-based inflammatory reflex are physiological regulators of inflammatory responses and cytokine production. In transplantation, neuro-immune communication could significantly impact the processes of host-pathogen defense, organ rejection, and wound healing. Emerging approaches to target the PNS such as bioelectronics could be useful in improving the outcome of transplantation. Therefore, understanding how the nervous system shapes the immune response could have important therapeutic ramifications for transplantation medicine. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  9. Molecular sex identification of dry human teeth specimens from Sokoto, Northwestern Nigeria.

    Science.gov (United States)

    Zagga, Ad; Ahmed, H Oon; Ismail, Sm; Tadros, Aa

    2014-05-01

    The advent of molecular techniques has revolutionized the ability of scientists to estimate the sex of individuals. Forensic odontology plays an important role in establishing the sex of victims with bodies mutilated beyond recognition due to major disaster. The genetic difference between males and females is defined by the presence or absence of the Y-chromosome. The use of alphoid-repeat primers in sex estimation was first applied on dried blood. Generally, the X, Y alphoid repeats blind test attest to the accuracy of genetic testing, and also point the potential for occasional error in morphometric sexing. To estimate genetic sex of dry human teeth specimens from Sokoto, Northwestern Nigeria, using polymerase chain reaction (PCR). A single-blind study of DNA analysis for sex estimation of nine dry human teeth specimens from Sokoto, Northwestern Nigeria, through PCR, using alphoid repeats primers, was undertaken. The genetic sex of each group of the teeth samples were accurately (100%) identified. For each group of teeth, PCR Sensitivity = 100%, Specificity = 0%, Predictive value of positive test = 100%, Predictive value of negative test = 0%, False positive rate = 0%, False negative rate = 0%, Efficiency of test = 100%. Fisher's exact probability test P = 1. Z-test: z- and P values were invalid. This study has demonstrated the successful use of alphoid-repeat primers in genetic sex identification of human dry teeth samples from Sokoto, Northwestern Nigeria. This is the first known study estimating the sex of human dry teeth specimens by means of PCR in Nigeria. There is need for further studies in Nigeria to complement the findings of this study.

  10. Interactive domains in the molecular chaperone human alphaB crystallin modulate microtubule assembly and disassembly.

    Directory of Open Access Journals (Sweden)

    Joy G Ghosh

    2007-06-01

    Full Text Available Small heat shock proteins regulate microtubule assembly during cell proliferation and in response to stress through interactions that are poorly understood.Novel functions for five interactive sequences in the small heat shock protein and molecular chaperone, human alphaB crystallin, were investigated in the assembly/disassembly of microtubules and aggregation of tubulin using synthetic peptides and mutants of human alphaB crystallin.The interactive sequence (113FISREFHR(120 exposed on the surface of alphaB crystallin decreased microtubule assembly by approximately 45%. In contrast, the interactive sequences, (131LTITSSLSSDGV(142 and (156ERTIPITRE(164, corresponding to the beta8 strand and the C-terminal extension respectively, which are involved in complex formation, increased microtubule assembly by approximately 34-45%. The alphaB crystallin peptides, (113FISREFHR(120 and (156ERTIPITRE(164, inhibited microtubule disassembly by approximately 26-36%, and the peptides (113FISREFHR(120 and (131LTITSSLSSDGV(142 decreased the thermal aggregation of tubulin by approximately 42-44%. The (131LTITSSLSSDGV(142 and (156ERTIPITRE(164 peptides were more effective than the widely used anti-cancer drug, Paclitaxel, in modulating tubulinmicrotubule dynamics. Mutagenesis of these interactive sequences in wt human alphaB crystallin confirmed the effects of the alphaB crystallin peptides on microtubule assembly/disassembly and tubulin aggregation. The regulation of microtubule assembly by alphaB crystallin varied over a narrow range of concentrations. The assembly of microtubules was maximal at alphaB crystallin to tubulin molar ratios between 1:4 and 2:1, while molar ratios >2:1 inhibited microtubule assembly.Interactive sequences on the surface of human alphaB crystallin collectively modulate microtubule assembly through a dynamic subunit exchange mechanism that depends on the concentration and ratio of alphaB crystallin to tubulin. These are the first

  11. The human melanoma side population displays molecular and functional characteristics of enriched chemoresistance and tumorigenesis.

    Science.gov (United States)

    Wouters, Jasper; Stas, Marguerite; Gremeaux, Lies; Govaere, Olivier; Van den Broeck, Anke; Maes, Hannelore; Agostinis, Patrizia; Roskams, Tania; van den Oord, Joost J; Vankelecom, Hugo

    2013-01-01

    Melanoma remains the most lethal skin cancer, mainly because of high resistance to therapy. Side population (SP) cells are found in many types of cancer and are usually enriched in therapy-resistant as well as tumorigenic cells. Here, we identified a Hoechst dye-effluxing SP in a large series of human melanoma samples representing different progression phases. The SP size did not change with disease stage but was correlated with the prognostic "Breslow's depth" in the primary (cutaneous) tumors. When injected into immunodeficient mice, the SP generated larger tumors than the bulk "main population" (MP) melanoma cells in two consecutive generations, and showed tumorigenic capacity at lower cell numbers than the MP. In addition, the SP reconstituted the heterogeneous composition of the human A375 melanoma cell line, and its clonogenic activity was 2.5-fold higher than that of the MP. Gene-expression analysis revealed upregulated expression in the melanoma SP (versus the MP) of genes associated with chemoresistance and anti-apoptosis. Consistent with these molecular characteristics, the SP increased in proportion when A375 cells were exposed to the melanoma standard chemotherapeutic agent dacarbazine, and to the aggravating condition of hypoxia. In addition, the SP showed enhanced expression of genes related to cell invasion and migration, as well as to putative (melanoma) cancer stem cells (CSC) including ABCB1 and JARID1B. ABCB1 immunoreactivity was detected in a number of tumor cells in human melanomas, and in particular in clusters at the invasive front of the primary tumors. Together, our findings support that the human melanoma SP is enriched in tumorigenic and chemoresistant capacity, considered key characteristics of CSC. The melanoma SP may therefore represent an interesting therapeutic target.

  12. Gene signatures associated with mouse postnatal hindbrain neural stem cells and medulloblastoma cancer stem cells identify novel molecular mediators and predict human medulloblastoma molecular classification.

    Science.gov (United States)

    Corno, Daniela; Daniela, Corno; Pala, Mauro; Cominelli, Manuela; Cipelletti, Barbara; Leto, Ketty; Croci, Laura; Barili, Valeria; Brandalise, Federico; Melzi, Raffaella; Di Gregorio, Alessandra; Sergi, Lucia Sergi; Politi, Letterio Salvatore; Piemonti, Lorenzo; Bulfone, Alessandro; Rossi, Paola; Rossi, Ferdinando; Consalez, Gian Giacomo; Poliani, Pietro Luigi; Galli, Rossella

    2012-06-01

    Medulloblastoma arises from mutations occurring in stem/progenitor cells located in restricted hindbrain territories. Here we report that the mouse postnatal ventricular zone lining the IV ventricle also harbors bona fide stem cells that, remarkably, share the same molecular profile with cerebellar white matter-derived neural stem cells (NSC). To identify novel molecular mediators involved in medulloblastomagenesis, we compared these distinct postnatal hindbrain-derived NSC populations, which are potentially tumor initiating, with murine compound Ptch/p53 mutant medulloblastoma cancer stem cells (CSC) that faithfully phenocopy the different variants of human medulloblastoma in vivo. Transcriptome analysis of both hindbrain NSCs and medulloblastoma CSCs resulted in the generation of well-defined gene signatures, each reminiscent of a specific human medulloblastoma molecular subclass. Most interestingly, medulloblastoma CSCs upregulated developmentally related genes, such as Ebfs, that were shown to be highly expressed in human medulloblastomas and play a pivotal role in experimental medullo-blastomagenesis. These data indicate that gene expression analysis of medulloblastoma CSCs holds great promise not only for understanding functional differences between distinct CSC populations but also for identifying meaningful signatures that might stratify medulloblastoma patients beyond histopathologic staging.

  13. Neuro-invasion by a ‘Trojan Horse’ strategy and vasculopathy during intrauterine flavivirus infection

    Science.gov (United States)

    Bielefeldt-Ohmann, Helle; Smirnova, Natalia P; Tolnay, Airn-Elizabeth; Webb, Brett T; Antoniazzi, Alfredo Q; van Campen, Hana; Hansen, Thomas R

    2012-01-01

    The central nervous system (CNS) is a major target of several important human and animal viral pathogens causing congenital infections. However, despite the importance of neuropathological outcomes, for humans in particular, the pathogenesis, including mode of neuro-invasion, remains unresolved for most congenital virus infections. Using a natural model of congenital infection with an RNA virus, bovine viral diarrhoea virus in pregnant cattle, we sought to delineate the timing and mode of virus neuro-invasion of and spread within the brain of foetuses following experimental respiratory tract infection of the dams at day 75 of pregnancy, a time of maximal risk of tissue pathology without foetal death. Virus antigen was first detected in the foetal brains 14 days postinfection of dams and was initially restricted to amoeboid microglial cells in the periventricular germinal layer. The appearance of these cells was preceded by or concurrent with vasculopathy in the same region. While the affected microvessels were negative for virus antigen, they expressed high levels of the type I interferon-stimulated protein ISG15 and eventually disappeared in parallel with the appearance of microcavitary lesions. Subsequently, the virus spread to neurons and other glial cells. Our findings suggest that the virus enters the CNS via infected microglial precursors, the amoeboid microglial cells, in a ‘Trojan horse’ mode of invasion and that the microcavitary lesions are associated with loss of periventricular microvasculature, perhaps as a consequence of high, unrestricted induction of interferon-regulated proteins. PMID:22264283

  14. Very stable high molecular mass multiprotein complex with DNase and amylase activities in human milk.

    Science.gov (United States)

    Soboleva, Svetlana E; Dmitrenok, Pavel S; Verkhovod, Timofey D; Buneva, Valentina N; Sedykh, Sergey E; Nevinsky, Georgy A

    2015-01-01

    For breastfed infants, human milk is more than a source of nutrients; it furnishes a wide array of proteins, peptides, antibodies, and other components promoting neonatal growth and protecting infants from viral and bacterial infection. It has been proposed that most biological processes are performed by protein complexes. Therefore, identification and characterization of human milk components including protein complexes is important for understanding the function of milk. Using gel filtration, we have purified a stable high molecular mass (~1000 kDa) multiprotein complex (SPC) from 15 preparations of human milk. Light scattering and gel filtration showed that the SPC was stable in the presence of high concentrations of NaCl and MgCl2 but dissociated efficiently under the conditions that destroy immunocomplexes (2 M MgCl2 , 0.5 M NaCl, and 10 mM DTT). Such a stable complex is unlikely to be a casual associate of different proteins. The relative content of the individual SPCs varied from 6% to 25% of the total milk protein. According to electrophoretic and mass spectrometry analysis, all 15 SPCs contained lactoferrin (LF) and α-lactalbumin as major proteins, whereas human milk albumin and β-casein were present in moderate or minor amounts; a different content of IgGs and sIgAs was observed. All SPCs efficiently hydrolyzed Plasmid supercoiled DNA and maltoheptaose. Some freshly prepared SPC preparations contained not only intact LF but also small amounts of its fragments, which appeared in all SPCs during their prolonged storage; the fragments, similar to intact LF, possessed DNase and amylase activities. LF is found in human epithelial secretions, barrier body fluids, and in the secondary granules of leukocytes. LF is a protein of the acute phase response and nonspecific defense against different types of microbial and viral infections. Therefore, LF complexes with other proteins may be important for its functions not only in human milk. Copyright © 2014

  15. Vasculogenesis, angiogenesis and the molecular organisation of endothelial junctions in the early human placenta.

    Science.gov (United States)

    Leach, Lopa; Babawale, Michael O; Anderson, Mark; Lammiman, Michael

    2002-01-01

    Vasculogenesis and angiogenesis are regulated by the capacity of endothelial cells to adhere to each other and form new tubes. The presence and role of junctional adhesion molecules during physiological vasculogenesis is unknown. Using ultrastructural and immunocytochemical approaches, we compared the junctional phenotype of developing vessels of the first-trimester human placenta with vessels in the last trimester; the latter include newly formed terminal capillaries and the quiescent vascular bed. First-trimester placental vessels contained the adherens junctional molecules, vascular endothelial cadherin and alpha- and beta-catenin but lacked plakoglobin, the component of fully differentiated adherens junctions. Furthermore, these vessels did not contain the transmembrane tight junctional molecules occludin and claudin-1 and -2. This profile reflects the phenotype of terminal capillaries but differs from large vessels of the full-term placenta. Electron microscopic studies revealed that endothelial tight junctions are present in the first-trimester placenta. Thus, occludin and claudin-1 appear to play no part in the formation of endothelial tight junctions, but are a later requirement. In the early placenta, the predominant growth factor appears to be vascular endothelial growth factor (VEGF), whilst at term, angiopoietin-1 was present in large vessels, with intense angiopoietin-2 immunofluorescence (and VEGF) located in terminal villous capillaries. Thus, endothelial junctions in the human placenta possess two distinct molecular phenotypes, i.e. stable or dynamic, dependent on maturity and plasticity. These distinct phenotypes may be influenced by the angiopoietins/VEGF present in the placenta. Copyright 2002 S. Karger AG, Basel

  16. Molecular cytogenetic analysis of human blastocysts andcytotrophoblasts by multi-color FISH and Spectra Imaging analyses

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Jingly F.; Ferlatte, Christy; Baumgartner, Adolf; Jung,Christine J.; Nguyen, Ha-Nam; Chu, Lisa W.; Pedersen, Roger A.; Fisher,Susan J.; Weier, Heinz-Ulrich G.

    2006-02-08

    Numerical chromosome aberrations in gametes typically lead to failed fertilization, spontaneous abortion or a chromosomally abnormal fetus. By means of preimplantation genetic diagnosis (PGD), we now can screen human embryos in vitro for aneuploidy before transferring the embryos to the uterus. PGD allows us to select unaffected embryos for transfer and increases the implantation rate in in vitro fertilization programs. Molecular cytogenetic analyses using multi-color fluorescence in situ hybridization (FISH) of blastomeres have become the major tool for preimplantation genetic screening of aneuploidy. However, current FISH technology can test for only a small number of chromosome abnormalities and hitherto failed to increase the pregnancy rates as expected. We are in the process of developing technologies to score all 24 chromosomes in single cells within a 3 day time limit, which we believe is vital to the clinical setting. Also, human placental cytotrophoblasts (CTBs) at the fetal-maternal interface acquire aneuploidies as they differentiate to an invasive phenotype. About 20-50% of invasive CTB cells from uncomplicated pregnancies were found aneuploidy, suggesting that the acquisition of aneuploidy is an important component of normal placentation, perhaps limiting the proliferative and invasive potential of CTBs. Since most invasive CTBs are interphase cells and possess extreme heterogeneity, we applied multi-color FISH and repeated hybridizations to investigate individual CTBs. In summary, this study demonstrates the strength of Spectral Imaging analysis and repeated hybridizations, which provides a basis for full karyotype analysis of single interphase cells.

  17. Energetic and molecular water permeation mechanisms of the human red blood cell urea transporter B.

    Science.gov (United States)

    Azouzi, Slim; Gueroult, Marc; Ripoche, Pierre; Genetet, Sandrine; Colin Aronovicz, Yves; Le Van Kim, Caroline; Etchebest, Catherine; Mouro-Chanteloup, Isabelle

    2013-01-01

    Urea transporter B (UT-B) is a passive membrane channel that facilitates highly efficient permeation of urea. In red blood cells (RBC), while the major function of UT-B is to transport urea, it is assumed that this protein is able to conduct water. Here, we have revisited this last issue by studying RBCs and ghosts from human variants with defects of aquaporin 1 (AQP1) or UT-B. We found that UT-B's osmotic water unit permeability (pfunit) is similar to that of AQP1. The determination of diffusional permeability coefficient (Pd) allowed the calculation of the Pf/Pd ratio, which is consistent with a single-file water transport. Molecular dynamic simulations of water conduction through human UT-B confirmed the experimental finding. From these results, we propose an atomistic description of water-protein interactions involved in this permeation. Inside the UT-B pore, five water molecules were found to form a single-file and move rapidly along a channel by hydrogen bond exchange involving two critical threonines. We further show that the energy barrier for water located in the central region coincides with a water dipole reorientation, which can be related to the proton exclusion observed experimentally. In conclusion, our results indicate that UT-B should be considered as a new member of the water channel family.

  18. Modelling human behaviour in a bumper car ride using molecular dynamics tools: a student project

    Science.gov (United States)

    Buendía, Jorge J.; Lopez, Hector; Sanchis, Guillem; Pardo, Luis Carlos

    2017-05-01

    Amusement parks are excellent laboratories of physics, not only to check physical laws, but also to investigate if those physical laws might also be applied to human behaviour. A group of Physics Engineering students from Universitat Politècnica de Catalunya has investigated if human behaviour, when driving bumper cars, can be modelled using tools borrowed from the analysis of molecular dynamics simulations, such as the radial and angular distribution functions. After acquiring several clips and obtaining the coordinates of the cars, those magnitudes are computed and analysed. Additionally, an analogous hard disks system is simulated to compare its distribution functions to those obtained from the cars’ coordinates. Despite the clear difference between bumper cars and a hard disk-like particle system, the obtained distribution functions are very similar. This suggests that there is no important effect of the individuals in the collective behaviour of the system in terms of structure. The research, performed by the students, has been undertaken in the frame of a motivational project designed to approach the scientific method for university students named FISIDABO. This project offers both the logistical and technical support to undertake the experiments designed by students at the amusement park of Barcelona TIBIDABO and accompanies them all along the scientific process.

  19. Canine spontaneous head and neck squamous cell carcinomas represent their human counterparts at the molecular level.

    Directory of Open Access Journals (Sweden)

    Deli Liu

    2015-06-01

    Full Text Available Spontaneous canine head and neck squamous cell carcinoma (HNSCC represents an excellent model of human HNSCC but is greatly understudied. To better understand and utilize this valuable resource, we performed a pilot study that represents its first genome-wide characterization by investigating 12 canine HNSCC cases, of which 9 are oral, via high density array comparative genomic hybridization and RNA-seq. The analyses reveal that these canine cancers recapitulate many molecular features of human HNSCC. These include analogous genomic copy number abnormality landscapes and sequence mutation patterns, recurrent alteration of known HNSCC genes and pathways (e.g., cell cycle, PI3K/AKT signaling, and comparably extensive heterogeneity. Amplification or overexpression of protein kinase genes, matrix metalloproteinase genes, and epithelial-mesenchymal transition genes TWIST1 and SNAI1 are also prominent in these canine tumors. This pilot study, along with a rapidly growing body of literature on canine cancer, reemphasizes the potential value of spontaneous canine cancers in HNSCC basic and translational research.

  20. Canine spontaneous head and neck squamous cell carcinomas represent their human counterparts at the molecular level.

    Science.gov (United States)

    Liu, Deli; Xiong, Huan; Ellis, Angela E; Northrup, Nicole C; Dobbin, Kevin K; Shin, Dong M; Zhao, Shaying

    2015-06-01

    Spontaneous canine head and neck squamous cell carcinoma (HNSCC) represents an excellent model of human HNSCC but is greatly understudied. To better understand and utilize this valuable resource, we performed a pilot study that represents its first genome-wide characterization by investigating 12 canine HNSCC cases, of which 9 are oral, via high density array comparative genomic hybridization and RNA-seq. The analyses reveal that these canine cancers recapitulate many molecular features of human HNSCC. These include analogous genomic copy number abnormality landscapes and sequence mutation patterns, recurrent alteration of known HNSCC genes and pathways (e.g., cell cycle, PI3K/AKT signaling), and comparably extensive heterogeneity. Amplification or overexpression of protein kinase genes, matrix metalloproteinase genes, and epithelial-mesenchymal transition genes TWIST1 and SNAI1 are also prominent in these canine tumors. This pilot study, along with a rapidly growing body of literature on canine cancer, reemphasizes the potential value of spontaneous canine cancers in HNSCC basic and translational research.

  1. Molecular characterisation of stromal populations derived from human embryonic stem cells

    DEFF Research Database (Denmark)

    Harkness, L.; Twine, N. A.; Abu Dawud, R.

    2015-01-01

    Human bone marrow-derived stromal (skeletal) stem cells (BM-hMSC) are being employed in an increasing number of clinical trials for tissue regeneration. A limiting factor for their clinical use is the inability to obtain sufficient cell numbers. Human embryonic stem cells (hESC) can provide...... an unlimited source of clinical grade cells for therapy. We have generated MSC-like cells from hESC (called here hESC-stromal) that exhibit surface markers and differentiate to osteoblasts and adipocytes, similar to BM-hMSC. In the present study, we used microarray analysis to compare the molecular phenotype...... of hESC-stromal and immortalised BM-hMSC cells (hMSC-TERT). Of the 7379 genes expressed above baseline, only 9.3% of genes were differentially expressed between undifferentiated hESC-stromal and BM-hMSC. Following ex vivo osteoblast induction, 665 and 695 genes exhibited >. 2-fold change (FC) in h...

  2. The gating mechanism of the human aquaporin 5 revealed by molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Lorant Janosi

    Full Text Available Aquaporins are protein channels located across the cell membrane with the role of conducting water or other small sugar alcohol molecules (aquaglyceroporins. The high-resolution X-ray structure of the human aquaporin 5 (HsAQP5 shows that HsAQP5, as all the other known aquaporins, exhibits tetrameric structure. By means of molecular dynamics simulations we analyzed the role of spontaneous fluctuations on the structural behavior of the human AQP5. We found that different conformations within the tetramer lead to a distribution of monomeric channel structures, which can be characterized as open or closed. The switch between the two states of a channel is a tap-like mechanism at the cytoplasmic end which regulates the water passage through the pore. The channel is closed by a translation of the His67 residue inside the pore. Moreover, water permeation rate calculations revealed that the selectivity filter, located at the other end of the channel, regulates the flow rate of water molecules when the channel is open, by locally modifying the orientation of His173. Furthermore, the calculated permeation rates of a fully open channel are in good agreement with the reported experimental value.

  3. Neuro-Linguistic Programming: Developing Effective Communication in the Classroom.

    Science.gov (United States)

    Torres, Cresencio; Katz, Judy H.

    Neuro-Linguistic Programming (NLP) is a method that teachers can use to increase their communication effectiveness by matching their communication patterns with those of their students. The basic premise of NLP is that people operate and make sense of their experience through information received from the world around them. This information is…

  4. PsychoNeuroImmunology Research Society's Norman Cousins Award.

    Science.gov (United States)

    2015-01-01

    Dr. Rainer H. Straub, University Hospital, Regensburg, Germany, is the recipient of the 2015 Norman Cousins Award and will present the memorial lecture at the PsychoNeuroImmunology Research Society (PNIRS) meeting, June 3–6, Seattle, WA. The Norman Cousins award is the highest honor bestowed by the PNIRS and recognizes sustained and outstanding research contributions in psychoneuroimmunology.

  5. 1 RESEARCH ARTICLE Neuro-Fuzzy Model of Homocysteine ...

    Indian Academy of Sciences (India)

    2017-03-10

    Mar 10, 2017 ... homeostasis by SHMT1 C1420T or increased flux of folate towards remethylation due to. TYMS 5'-UTR 28bp tandem repeat or non-vegetarian diet can lower homocysteine levels. Keywords: Homocysteine; Multiple Linear Regression; Neuro-Fuzzy design; diet. Introduction. Homocysteine is a non-dietary ...

  6. [Neuro-muscular apparatus state in lumbosacral radiculopathy in miners].

    Science.gov (United States)

    Battakova, Sh B; Amanbekov, U A; Otarbaeva, M B; Fazylova, M D; Sraĭmanov, K S; Miianova, G A; Kozhakhmetova, K M

    2008-01-01

    Based on clinical and electrophysiologic studies, the authors analysed neuro-muscular apparatus of "spinal center--periphery" axis for miners with radicular pain caused by occupational lumbosacral radiculopathy. Findings are that constantly irritated receptors in lumbar motor segment during occupational activities alter habitual motor stereotype and cause specific compensatory muscular reactions, rearrangement of motor activity in segmental apparatus.

  7. Neuro-fuzzy model for evaluating the performance of processes ...

    Indian Academy of Sciences (India)

    In this work an Adaptive Neuro-Fuzzy Inference System (ANFIS) was used to model the periodic performance of some multi-input single-output (MISO) processes, namely: brewery operations (case study 1) and soap production (case study 2) processes. Two ANFIS models were developed to model the performance of the ...

  8. Industry progress report on neuro-oncology: a biotech update.

    Science.gov (United States)

    Haber, Jessica S; Banu, Matei A; Ray, Ashley; Kesavabhotla, Kartik; Boockvar, John A

    2013-04-01

    With steadily rising revenue and large numbers of clinical trials utilizing novel treatment strategies, the field of neuro-oncology is at the core of the growing cancer therapy industry. In June 2012, the Weill Cornell Brain and Tumor Center hosted the first Brain Tumor Biotech Summit as a forum for fostering and encouraging collaboration between researches and investors to accelerate novel treatments for brain cancer. This event brought together neuro-oncologists, neurosurgeons, academicians, entrepreneurs, non-profits, CEOs and investors in an attempt to bring innovative treatments and concepts to the fore. Specific subjects presented at the meeting included new surgical devices and delivery techniques, targeted therapeutics, immunotherapy, and stem cell biology. The mission of the summit was to provide opportunities for researchers in neuro-oncology to directly interact with leaders from the investment community with insight into the commercial aspects of our work. Our shared goal is to shorten the time for basic science ideas to be translated into the clinical setting. The following serves as a progress report on the biotech industry in neuro-oncology, as presented at the Brain Tumor Biotech Summit.

  9. Neuro-fuzzy system for chaotic time series forecasting

    Science.gov (United States)

    Masulli, Francesco; Studer, Leonard

    1997-10-01

    We report on an on-going study to assess potential benefits using soft computing methods in forecasting problems. Our goal is to forecast natural phenomena represented by time series that show chaotic features. We use a neuro-fuzzy system for its ability to adapt to numerical data and for the possibility to input and extract expert knowledge expressed in words. We present results of experiments designed to study how to shape a neuro-fuzzy systems to forecast chaotic time series. Our main conclusions are: (1) The neuro-fuzzy system is able to forecast a synthetic chaotic time series with high accuracy if the number of inputs and the time delay between them are chosen adequately. (2) The Takens-Mane theorem from chaos theory gives a useful lower bound on the minimal number of inputs. (3) The time delay between the inputs can not be set a priori. It has to be tuned for every different times series. (4) The number of fuzzy rules seems related to the size of the learning set and not to the structure of the chaotic dynamical system. We tentatively try to interpret the rules that the neuro-fuzzy system has learned. Finally we discuss the adequacy of the whole set of fuzzy rules to forecast locally the dynamical system.

  10. Chips of Hope: Neuro-Electronic Hybrids for Brain Repair

    Science.gov (United States)

    Ben-Jacob, Eshel

    2010-03-01

    The field of Neuro-Electronic Hybrids kicked off 30 years ago when researchers in the US first tweaked the technology of recording and stimulation of networks of live neurons grown in a Petri dish and interfaced with a computer via an array of electrodes. Since then, many researchers have searched for ways to imprint in neural networks new ``memories" without erasing old ones. I will describe our new generation of Neuro-Electronic Hybrids and how we succeeded to turn them into the first learning Neurochips - memory and information processing chips made of live neurons. To imprint multiple memories in our new chip we used chemical stimulation at specific locations that were selected by analyzing the networks activity in real time according to our new information encoding principle. Currently we develop new-generation of neuro chips using special carbon nano tubes (CNT). These electrodes enable to engineer the networks topology and efficient electrical interfacing with the neurons. This advance bears the promise to pave the way for building a new experimental platform for testing new drugs and developing new methods for neural networks repair and regeneration. Looking into the future, the development brings us a step closer towards the dream of Brain Repair by implementable Neuro-Electronic hybrid chips.

  11. Aquatic intervention in children with neuro-motor impairments

    NARCIS (Netherlands)

    Getz, M.D.

    2006-01-01

    The present thesis addresses the influence of aquatic interventions on motor performance of children with neuro-motor deficiencies in a functional context. The theoretical framework is based on a functional approach in compliance to the International Classification of Function and Disability (ICF).

  12. The role of neuro-electrophysiological diagnostic tests in clinical ...

    African Journals Online (AJOL)

    Objective: To summarise and discuss the role of neuro-electrophysiological diagnostic tests in clinical medicine. Data Sources: Published original research and reviews to date. Study Selection: The review was with emphasis on diagnosis of peripheral neuropathic and neuromuscular disorders. Data extraction and ...

  13. Neuro-vascular injuries associated with limb fractures | Mirdad | East ...

    African Journals Online (AJOL)

    Neuro-vascular injuries associated with limb fractures. ... PROMOTING ACCESS TO AFRICAN RESEARCH. AFRICAN JOURNALS ... Subjects: Forty three patients with bone fractures associated with vascular and peripheral nerve injury seen at the Emergency Room of Assir Central Hospital from 1990 to 1999. There were ...

  14. Cognitive Neuro-Assessment In Nigerian Africans – Predictive ...

    African Journals Online (AJOL)

    The neuro-cognitive assessment has evolved from traditional psychometric testing to computerized testing which is able to detect subtle cognitive changes. The objective of this study is to determine the predictive validity of a computerized cognitive test battery, the Iron Psychology (acronym FePsy) among Nigerian Africans ...

  15. Neuro-Linguistic Programming Treatment for Anxiety: Magic or Myth?

    Science.gov (United States)

    Krugman, Martin; And Others

    1985-01-01

    Compared neuro-linguistic programing treatment for anxiety with self-control desensitization of equal duration and a waiting-list control group in treating public speaking anxiety. Results indicated that neither treatment was more effective in reducing anxiety than merely waiting for one hour. (Author/MCF)

  16. Grammar disruption in a patient with Neuro-Sweet syndrome

    NARCIS (Netherlands)

    Marien, Peter; Tops, Wim; Crols, Roel; Jonkers, Roel; De Deyn, Peter P.; Verhoeven, Jo

    2012-01-01

    This paper for the first time reports detailed neurolinguistic findings in a patient with Neuro-Sweet syndrome. In this patient the presenting symptoms of central nervous system (CNS) involvement primarily consisted of a selective grammar deficit restricted to spontaneous speech. On MRI a left

  17. Primary headache disorders and neuro-ophthalmologic manifestations

    Directory of Open Access Journals (Sweden)

    Schwartz DP

    2012-09-01

    Full Text Available Daniel P Schwartz, Matthew S RobbinsDepartment of Neurology, Montefiore Headache Center, Albert Einstein College of Medicine, Bronx, NY, USAAbstract: Headache is an extraordinarily common complaint presenting to medical practitioners in all arenas and specialties, particularly primary care physicians, neurologists, and ophthalmologists. A wide variety of headache disorders may manifest with a myriad of neuro-ophthalmologic symptoms, including orbital pain, disturbances of vision, aura, photophobia, lacrimation, conjunctival injection, ptosis, and other manifestations. The differential diagnosis in these patients is broad and includes both secondary, or symptomatic, and primary headache disorders. Awareness of the headache patterns and associated symptoms of these various disorders is essential to achieve the correct diagnosis. This paper reviews the primary headache disorders that prominently feature neuro-ophthalmologic manifestations, including migraine, the trigeminal autonomic cephalalgias, and hemicrania continua. Migraine variants with prominent neuro-ophthalmologic symptoms including aura without headache, basilar-type migraine, retinal migraine, and ophthalmoplegic migraine are also reviewed. This paper focuses particularly on the symptomatology of these primary headache disorders, but also discusses their epidemiology, clinical features, and treatment.Keywords: headache, migraine, trigeminal autonomic cephalalgias, neuro-ophthalmologic, aura, photophobia

  18. Modeling neuro-vascular coupling in rat cerebellum

    DEFF Research Database (Denmark)

    Rasmussen, Tina; Holstein-Rathlou, Niels-Henrik; Lauritzen, Martin

    2009-01-01

    We investigated the quantitative relation between neuronal activity and blood flow by means of a general parametric mathematical model which described the neuro-vascular system as being dynamic, linear, time-invariant, and subjected to additive noise. The model was constructed from measurements b...

  19. Molecular Characterisation of Salmonella enterica Serovar Typhi Isolated from Typhoidial Humans

    Directory of Open Access Journals (Sweden)

    Arunava Das

    2012-09-01

    Full Text Available Aims: Salmonella enterica serovar Typhi is the major causative agent for typhoidial fever around the globe among human population reported till date. Present research work was carried out for detection and molecular characterisation of Salmonella enterica serovar Typhi isolated from humans with Typhoidial fever by biochemical, phenotypical and virulence gene based polymerase chain reaction (PCR techniques. The isolated strains were also investigated for antibiotic susceptibility patterns as a control measure. Methodology and Results: A total of 16 clinical samples were collected from the same numbers of patients (7 males and 9 females from Coimbatore, Erode and Salem districts of Tamil Nadu and were processed via broth enrichment methods for isolation and identification of the causative agent S. enterica serovar Typhi. Microbiological and biochemical investigations revealed the presence of S. Typhi from 16 samples. The biotyping of the isolates showed that all the isolates belonged to biotype IV. The PCR analysis confirmed the presence of invA (Invasion gene, 244bp, tyv (Tyveloseepimerase gene, 615 bp, fliC-d (Phage-1 flagellin gene for d-antigen, 750 bp and viaB (Vi antigen gene, 439bp in all 16 clinical samples. The antibiotic susceptibility test that was carried out among the isolates against 12 antimicrobial agents, showed 100 % resistance to only ampicillin and 100 % sensitivity to carbenicillin, chloramphenicol, clindamycin, gentamycin, kanamycin and tetracycline.Conclusion, significance and impact of study: This study confirmed the association of virulent strains of S. enterica serovar Typhi from Typhoidial fever among human population and suggested that PCR based diagnostic could be very useful for the rapid detection of S. Typhi isolates. Present study emphasized the use of antibiotic like chloramphenicol or in combination with other antibiotics for the effective control of S. Typhi.

  20. Molecular response of the human diaphragm on different modes of mechanical ventilation.

    Science.gov (United States)

    Dermitzaki, Despina; Tzortzaki, Eleni; Soulitzis, Nikolaos; Neofytou, Eirini; Prinianakis, Georgios; Matalliotakis, Ioannis; Askitopoulou, Helen; Siafakas, Nikolaos M

    2013-01-01

    The mechanical stress that the human diaphragm is exposed to during mechanical ventilation affects a variety of processes, including signal transduction, gene expression, and angiogenesis. The study aim was to assess the change in the production of major angiogenic regulators [vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF2), and transforming growth factor beta 1 (TGFB1)] on the human diaphragm before and after contraction/relaxation cycles during mechanical ventilation. This observational study investigates the diaphragmatic mRNA expression of VEGF, FGF2, and TGFB1 in surgical patients receiving general anesthesia with controlled mechanical ventilation (CMV) with muscle relaxation (group A, n = 13), CMV without muscle relaxation (group B, n = 10), and pressure support of spontaneous breathing (group C, n = 9). Diaphragmatic samples were obtained from each patient at two time points: 30 min after the induction of anesthesia (t1) and 90 min after the first specimen collection (t2). No significant changes in the mRNA expression of VEGF, FGF2, and TGFB1 were documented in groups A and C between time points t1 and t2. In contrast, in group B, the mRNA levels of the above angiogenic factors were increased in time point t2 compared to t1, a finding which was statistically significant (pVEGF = 0.003, pFGF2 = 0.028, pTGFB1 = 0.001). These findings suggest that the molecular response of the human diaphragm before and after application of diverse modes of mechanical ventilation is different. Angiogenesis via the expression of VEGF, FGF2, and TGFB1 was only promoted in CMV without muscle relaxation, and this may have important clinical implications. Copyright © 2012 S. Karger AG, Basel.

  1. Challenges with defining response to antitumor agents in pediatric neuro-oncology: a report from the response assessment in pediatric neuro-oncology (RAPNO) working group.

    Science.gov (United States)

    Warren, Katherine E; Poussaint, Tina Y; Vezina, Gilbert; Hargrave, Darren; Packer, Roger J; Goldman, Stewart; Wen, Patrick Y; Pollack, Ian F; Zurakowski, David; Kun, Larry E; Prados, Michael D; Rutkowski, Stefan; Kieran, Mark W

    2013-09-01

    Criteria for new drug approval include demonstration of efficacy. In neuro-oncology, this is determined radiographically utilizing tumor measurements on MRI scans. Limitations of this method have been identified where drug activity is not reflected in decreased tumor size. The RANO (Response Assessment in Neuro-Oncology) working group was established to address limitations in defining endpoints for clinical trials in adult neuro-oncology and to develop standardized response criteria. RAPNO was subsequently established to address unique issues in pediatric neuro-oncology. The aim of this paper is to delineate response criteria issues in pediatric clinical trials as a basis for subsequent recommendations. Copyright © 2013 Wiley Periodicals, Inc.

  2. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone.

    OpenAIRE

    Adachi, A; Gendelman, H E; Koenig, S.; Folks, T; Willey, R; Rabson, A; Martin, M. A.

    1986-01-01

    We constructed an infectious molecular clone of acquired immunodeficiency syndrome-associated retrovirus. Upon transfection, this clone directed the production of infectious virus particles in a wide variety of cells in addition to human T4 cells. The progeny, infectious virions, were synthesized in mouse, mink, monkey, and several human non-T cell lines, indicating the absence of any intracellular obstacle to viral RNA or protein production or assembly. During the course of these studies, a ...

  3. Palliative Care Needs in the Neuro-ICU

    Science.gov (United States)

    Creutzfeldt, Claire J.; Engelberg, Ruth A.; Healey, Larry; Cheever, Chong (Sherry); Becker, Kyra J.; Holloway, Robert G.; Curtis, J. Randall

    2015-01-01

    Objective Patients admitted to the neurological or neurosurgical intensive care unit (neuro-ICU) are likely to have palliative care needs. The goals of this project are to encourage the ICU team to identify palliative care needs for patients and their families and potential ways to meet those needs. Design Quality improvement project using a parallel-group prospective cohort design. Setting Single neuro-ICU at a large, academic medical center. Patients All patients admitted to the neuro-ICU from September 1, 2013 to November 30, 2013. Intervention We developed a Palliative Care Needs Screening Tool consisting of 4 questions: (1) Does the patient have distressing physical or psychological symptoms? (2) Are there specific support needs for patient or family? (3) Are treatment options matched with patient-centered goals? (4) Are there disagreements among teams and family? We implemented this daily screening tool on morning rounds for 1 of 2 neurocritical care services that alternate admitting days to a single neuro-ICU. We examined prevalence and nature of palliative care needs and actions to address those needs, comparing the services with and without screening. Measurements and main results Over the 3-month period, 130 patients were admitted to the service with screening, and 132 patients to the service without screening. The two groups did not differ in regards to age, gender, Glasgow coma scale or diagnosis. Palliative care needs were identified in 62% of screened patients (80/130). Needs were mainly social support (53%) and establishing goals of care (28%). Screening was associated with more documented family conferences (p=0.019) and a trend towards more palliative care consultations (p=0.056). Conclusions We developed a brief palliative care needs screening tool that identified palliative care needs for 62% neuro-ICU patients. This tool was associated with actions to meet these needs, potentially improving care for patients and their families. PMID:25867905

  4. Molecular mechanism inhibiting human hepatocarcinoma cell invasion by 6-shogaol and 6-gingerol.

    Science.gov (United States)

    Weng, Chia-Jui; Chou, Chai-Ping; Ho, Chi-Tang; Yen, Gow-Chin

    2012-08-01

    We previously demonstrated that 6-shogaol and 6-gingerol, two active compounds in ginger (Zingiber officinale), possess antiinvasive activity against highly metastatic hepatoma cells. The aims of this study were to evaluate the inhibitory effect and molecular mechanism underlying the transcription and translation of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA) in Hep3B cells as well as the antiangiogenic activity of 6-gingerol and 6-shogaol. By gelatin zymography and luciferase reporter gene assays, we found that 6-gingerol and 6-shogaol regulate MMP-2/-9 transcription. Moreover, 6-gingerol directly decreased expression of uPA, but the 6-shogaol-mediated decrease in uPA was accompanied by up-regulation of plasminogen activator inhibitor (PAI)-1. 6-Gingerol and 6-shogaol concentrations of ≥ 10 μM and ≥ 2.5 μM, respectively, significantly inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling, the activation of NF-κB, and the translocation of NF-κB and STAT3. Incubation of 6-gingerol or 6-shogaol with human umbilical vein endothelial cells or rat aortas significantly attenuated tube formation. 6-Shogaol and 6-gingerol effectively inhibit invasion and metastasis of hepatocellular carcinoma through diverse molecular mechanisms, including inhibition of the MAPK and PI3k/Akt pathways and NF-κB and STAT3 activities to suppress expression of MMP-2/-9 and uPA and block angiogenesis. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Species identification and molecular typing of human Brucella isolates from Kuwait.

    Science.gov (United States)

    Mustafa, Abu S; Habibi, Nazima; Osman, Amr; Shaheed, Faraz; Khan, Mohd W

    2017-01-01

    Brucellosis is a zoonotic disease of major concern in Kuwait and the Middle East. Human brucellosis can be caused by several Brucella species with varying degree of pathogenesis, and relapses are common after apparently successful therapy. The classical biochemical methods for identification of Brucella are time-consuming, cumbersome, and provide information limited to the species level only. In contrast, molecular methods are rapid and provide differentiation at intra-species level. In this study, four molecular methods [16S rRNA gene sequencing, real-time PCR, enterobacterial repetitive intergenic consensus (ERIC)-PCR and multilocus variable-number tandem-repeat analysis (MLVA)-8, MLVA-11 and MLVA-16 were evaluated for the identification and typing of 75 strains of Brucella isolated in Kuwait. 16S rRNA gene sequencing of all isolates showed 90-99% sequence identity with B. melitensis and real-time PCR with genus- and species- specific primers identified all isolates as B. melitensis. The results of ERIC-PCR suggested the existence of 75 ERIC genotypes of B. melitensis with a discriminatory index of 0.997. Cluster classification of these genotypes divided them into two clusters, A and B, diverging at ~25%. The maximum number of genotypes (n = 51) were found in cluster B5. MLVA-8 analysis identified all isolates as B. melitensis, and MLVA-8, MLVA-11 and MLVA-16 typing divided the isolates into 10, 32 and 71 MLVA types, respectively. Furthermore, the combined minimum spanning tree analysis demonstrated that, compared to MLVA types discovered all over the world, the Kuwaiti isolates were a distinct group of MLVA-11 and MLVA-16 types in the East Mediterranean Region.

  6. Binding between Saikosaponin C and Human Serum Albumin by Fluorescence Spectroscopy and Molecular Docking

    Directory of Open Access Journals (Sweden)

    Yi-Cun Chen

    2016-01-01

    Full Text Available Saikosaponin C (SSC is one of the major active constituents of dried Radix bupleuri root (Chaihu in Chinese that has been widely used in China to treat a variety of conditions, such as liver disease, for many centuries. The binding of SSC to human serum albumin (HSA was explored by fluorescence, circular dichroism (CD, UV-vis spectrophotometry, and molecular docking to understand both the pharmacology and the basis of the clinical use of SSC/Chaihu. SSC produced a concentration-dependent quenching effect on the intrinsic fluorescence of HSA, accompanied by a blue shift in the fluorescence spectra. The Stern-Volmer equation showed that this quenching was dominated by static quenching. The binding constant of SSC with HSA was 3.72 × 103 and 2.99 × 103 L·mol−1 at 26 °C and 36 °C, respectively, with a single binding site on each SSC and HSA molecule. Site competitive experiments demonstrated that SSC bound to site I (subdomain IIA and site II (subdomain IIIA in HSA. Analysis of thermodynamic parameters indicated that hydrogen bonding and van der Waals forces were mostly responsible for SSC-HSA association. The energy transfer efficiency and binding distance between SSC and HSA was calculated to be 0.23 J and 2.61 nm at 26 °C, respectively. Synchronous fluorescence and CD measurements indicated that SSC affected HSA conformation in the SSC-HSA complex. Molecular docking supported the experimental findings in conformational changes, binding sites and binding forces, and revealed binding of SSC at the interface between subdomains IIA-IIB.

  7. In vivo mutations in human blood cells: Biomarkers for molecular epidemiology

    Energy Technology Data Exchange (ETDEWEB)

    Albertini, R.J.; Branda, R.F.; O' Neill, J.P. (Univ. of Vermont, Burlington (United States)); Nicklas, J.A.; Fuscoe, J.C. (Environmental Health Research and Testing, Inc., Research Triangle Park, NC (United States)); Skopek, T.R. (Univ. of North Carolina, Chapel Hill (United States))

    1993-03-01

    Mutations arising in vivo in recorder genes of human blood cells provide biomarkers for molecular epidemiology by serving as surrogates for cancer-causing genetic changes. Current markers include mutations of the glycophorin-A (GPA) or hemoglobin (Hb) genes, measured in red blood cells, or mutations of the hypoxanthine-guanine phosphoribosyltransferase (hprt) or HLA genes, measured in T-lymphocytes. Mean mutant frequencies (variant frequencies) for normal young adults are approximately: Hb (4 [times] 10[sup [minus]8]) < hprt (5 [times] 10[sup [minus]6]) = GPA (10 [times] 10[sup [minus]6]) < HLA (30 [times] 10[sup [minus]6]). Mutagen-exposed individuals show decided elevations. Molecular mutational spectra are also being defined. For the hprt marker system, about 15% of background mutations are gross structural alterations of the hprt gene (e.g., deletions); the remainder are point mutations (e.g., base substitutions or frameshifts). Ionizing radiations result in dose-related increases in total gene deletions. Large deletions may encompass several megabases as shown by co-deletions of linked markers. Possible hprt spectra for defining radiation and chemical exposures are being sought. In addition to their responsiveness to environmental mutagens/carcinogens, three additional findings suggest that the in vivo recorder mutations are relevant in vivo surrogates for cancer mutations. First, a large fraction of GPA and HLA mutations show exchanges due to homologous recombination, an important mutational event in cancer. Second, hprt mutations arise preferentially in dividing T-cells, which can accumulate additional mutations in the same clone, reminiscent of the multiple hits required in the evolution of malignancy. Finally, fetal hprt mutations frequently have characteristic deletions of hprt exons 2 and 3, which appear to be mediated by the VDJ recombinase that rearranges the T-cell receptor genes during thymic ontogeny. 60 refs., 3 tabs.

  8. Discovery of molecular markers to discriminate corneal endothelial cells in the human body.

    Directory of Open Access Journals (Sweden)

    Masahito Yoshihara

    Full Text Available The corneal endothelium is a monolayer of hexagonal corneal endothelial cells (CECs on the inner surface of the cornea. CECs are critical in maintaining corneal transparency through their barrier and pump functions. CECs in vivo have a limited capacity in proliferation, and loss of a significant number of CECs results in corneal edema called bullous keratopathy which can lead to severe visual loss. Corneal transplantation is the most effective method to treat corneal endothelial dysfunction, where it suffers from donor shortage. Therefore, regeneration of CECs from other cell types attracts increasing interests, and specific markers of CECs are crucial to identify actual CECs. However, the currently used markers are far from satisfactory because of their non-specific expression in other cell types. Here, we explored molecular markers to discriminate CECs from other cell types in the human body by integrating the published RNA-seq data of CECs and the FANTOM5 atlas representing diverse range of cell types based on expression patterns. We identified five genes, CLRN1, MRGPRX3, HTR1D, GRIP1 and ZP4 as novel markers of CECs, and the specificities of these genes were successfully confirmed by independent experiments at both the RNA and protein levels. Notably none of them have been documented in the context of CEC function. These markers could be useful for the purification of actual CECs, and also available for the evaluation of the products derived from other cell types. Our results demonstrate an effective approach to identify molecular markers for CECs and open the door for the regeneration of CECs in vitro.

  9. Molecular epidemiology of sexually transmitted human papillomavirus in a self referred group of women in Ireland.

    LENUS (Irish Health Repository)

    Menton, John F

    2009-01-01

    BACKGROUND: Human papillomavirus (HPV) causes cervical cancer and external genital warts. The purpose of this study is to document the genotype distribution of HPV in females aged between 18 and 34 who self-referred to an STI clinic with visible external genital warts (EGW). Scrapings were taken from visible external genital warts (EGW). These scrapings were analysed by PCR for the presence of HPV DNA. Positive samples were then genotyped by means of a commercially available assay (LiPA). A comparison of genotyping results determined by the LiPA assay and direct amplicon DNA sequencing was also performed. RESULTS: Ninety-two patients out of 105 samples (88%) had detectable levels of HPV DNA. The majority of individuals with EGW (66%) showed the presence of two or more genotypes. The most common HPV genotypes present in the study population were HPV-6, HPV-11, HPV-16, HPV-18, HPV-33 and HPV-53. Potential effects of vaccination on HPV molecular epidemiology indicate that 40% of the patients could have been protected from the high risk genotypes HPV-16 and HPV-18. CONCLUSION: This is the first report of the molecular epidemiology of external genital warts in women aged between 18 and 34 from Ireland based on results from a LiPA assay. The study shows that most individuals are infected with multiple genotypes including those with high oncogenic potential and that the newly available HPV vaccines could have a significant impact on prevalence of the most common HPV genotypes in this study population.

  10. Clinical and molecular epidemiology of human rhinovirus infections in patients with hematologic malignancy.

    Science.gov (United States)

    Jacobs, Samantha E; Lamson, Daryl M; Soave, Rosemary; Guzman, Brigitte Huertas; Shore, Tsiporah B; Ritchie, Ellen K; Zappetti, Dana; Satlin, Michael J; Leonard, John P; van Besien, Koen; Schuetz, Audrey N; Jenkins, Stephen G; George, Kirsten St; Walsh, Thomas J

    2015-10-01

    Human rhinoviruses (HRVs) are common causes of upper respiratory tract infection (URTI) in hematologic malignancy (HM) patients. Predictors of lower respiratory tract infection (LRTI) including the impact of HRV species and types are poorly understood. This study aims to describe the clinical and molecular epidemiology of HRV infections among HM patients. From April 2012-March 2013, HRV-positive respiratory specimens from symptomatic HM patients were molecularly characterized by analysis of partial viral protein 1 (VP1) or VP4 gene sequence. HRV LRTI risk-factors and outcomes were analyzed using multivariable logistic regression. One hundred and ten HM patients presented with HRV URTI (n=78) and HRV LRTI (n=32). Hypoalbuminemia (OR 3.0; 95% CI, 1.0-9.2; p=0.05) was independently associated with LRTI, but other clinical and laboratory markers of host immunity did not differ between patients with URTI versus LRTI. Detection of bacterial co-pathogens was common in LRTI cases (25%). Among 92 typeable respiratory specimens, there were 58 (64%) HRV-As, 12 (13%) HRV-Bs, and 21 (23%) HRV-Cs, and one Enterovirus 68. LRTI rates among HRV-A (29%), HRV-B (17%), and HRV-C (29%) were similar. HRV-A infections occurred year-round while HRV-B and HRV-C infections clustered in the late fall and winter. HRVs are associated with LRTI in HM patients. Illness severity is not attributable to specific HRV species or types. The frequent detection of bacterial co-pathogens in HRV LRTIs further substantiates the hypothesis that HRVs predispose to bacterial superinfection of the lower airways, similar to that of other community-acquired respiratory viruses. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Discovery of molecular markers to discriminate corneal endothelial cells in the human body.

    Science.gov (United States)

    Yoshihara, Masahito; Ohmiya, Hiroko; Hara, Susumu; Kawasaki, Satoshi; Hayashizaki, Yoshihide; Itoh, Masayoshi; Kawaji, Hideya; Tsujikawa, Motokazu; Nishida, Kohji

    2015-01-01

    The corneal endothelium is a monolayer of hexagonal corneal endothelial cells (CECs) on the inner surface of the cornea. CECs are critical in maintaining corneal transparency through their barrier and pump functions. CECs in vivo have a limited capacity in proliferation, and loss of a significant number of CECs results in corneal edema called bullous keratopathy which can lead to severe visual loss. Corneal transplantation is the most effective method to treat corneal endothelial dysfunction, where it suffers from donor shortage. Therefore, regeneration of CECs from other cell types attracts increasing interests, and specific markers of CECs are crucial to identify actual CECs. However, the currently used markers are far from satisfactory because of their non-specific expression in other cell types. Here, we explored molecular markers to discriminate CECs from other cell types in the human body by integrating the published RNA-seq data of CECs and the FANTOM5 atlas representing diverse range of cell types based on expression patterns. We identified five genes, CLRN1, MRGPRX3, HTR1D, GRIP1 and ZP4 as novel markers of CECs, and the specificities of these genes were successfully confirmed by independent experiments at both the RNA and protein levels. Notably none of them have been documented in the context of CEC function. These markers could be useful for the purification of actual CECs, and also available for the evaluation of the products derived from other cell types. Our results demonstrate an effective approach to identify molecular markers for CECs and open the door for the regeneration of CECs in vitro.

  12. Molecular epidemiology of human immunodeficiency virus type 1 in Guangdong province of southern China.

    Directory of Open Access Journals (Sweden)

    Song Chen

    Full Text Available BACKGROUND: Although the outbreak of human immunodeficiency virus type 1 (HIV-1 in Guangdong has been documented for more than a decade, the molecular characteristics of such a regional HIV-1 epidemic remained unknown. METHODOLOGY/PRINCIPAL FINDINGS: By sequencing of HIV-1 pol/env genes and phylogenetic analysis, we performed a molecular epidemiologic study in a representative subset (n  = 200 of the 508 HIV-1-seropositive individuals followed up at the center for HIV/AIDS care and treatment of Guangzhou Hospital of Infectious Diseases. Of 157 samples (54.1% heterosexual acquired adults, 20.4% needle-sharing drug users, 5.7% receivers of blood transfusion, 1.3% men who have sex with men, and 18.5% remained unknown with successful sequencing for both pol and env genes, 105 (66.9% HIV-1 subtype CRF01_AE and 24 (15.3% CRF07_BC, 9 (5.7% B', 5 (3.2% CRF08_BC, 5 (3.2% B, 1 (0.6% C, 3 (1.9% CRF02_AG, and 5 (3.2% inter-region recombinants were identified within pol/env sequences. Thirteen (8.3% samples (3 naïves, 6 and 5 received with antiretroviral treatment [ART] 1-21 weeks and ≥24 weeks respectively showed mutations conferring resistance to nucleoside/nonnucleoside reverse transcriptase inhibitors or protease inhibitors. Among 63 ART-naïve patients, 3 (4.8% showed single or multiple drug resistant mutations. Phylogenetic analysis showed 8 small clusters (2-3 sequences/cluster with only 17 (10.8% sequences involved. CONCLUSION/SIGNIFICANCE: This study confirms that sexual transmission with dominant CRF01_AE strain is a major risk for current HIV-1 outbreak in the Guangdong's general population. The transmission with drug-resistant variants is starting to emerge in this region.

  13. Molecular epidemiology of sexually transmitted human papillomavirus in a self referred group of women in Ireland

    Directory of Open Access Journals (Sweden)

    Horgan Mary

    2009-07-01

    Full Text Available Abstract Background Human papillomavirus (HPV causes cervical cancer and external genital warts. The purpose of this study is to document the genotype distribution of HPV in females aged between 18 and 34 who self-referred to an STI clinic with visible external genital warts (EGW. Scrapings were taken from visible external genital warts (EGW. These scrapings were analysed by PCR for the presence of HPV DNA. Positive samples were then genotyped by means of a commercially available assay (LiPA. A comparison of genotyping results determined by the LiPA assay and direct amplicon DNA sequencing was also performed. Results Ninety-two patients out of 105 samples (88% had detectable levels of HPV DNA. The majority of individuals with EGW (66% showed the presence of two or more genotypes. The most common HPV genotypes present in the study population were HPV-6, HPV-11, HPV-16, HPV-18, HPV-33 and HPV-53. Potential effects of vaccination on HPV molecular epidemiology indicate that 40% of the patients could have been protected from the high risk genotypes HPV-16 and HPV-18. Conclusion This is the first report of the molecular epidemiology of external genital warts in women aged between 18 and 34 from Ireland based on results from a LiPA assay. The study shows that most individuals are infected with multiple genotypes including those with high oncogenic potential and that the newly available HPV vaccines could have a significant impact on prevalence of the most common HPV genotypes in this study population.

  14. Molecular signature of cell cycle exit induced in human T lymphoblasts by IL-2 withdrawal

    Directory of Open Access Journals (Sweden)

    Pfeifer Aleksandra

    2009-06-01

    Full Text Available Abstract Background The molecular mechanisms of cell cycle exit are poorly understood. Studies on lymphocytes at cell cycle exit after growth factor deprivation have predominantly focused on the initiation of apoptosis. We aimed to study gene expression profile of primary and immortalised IL-2-dependent human T cells forced to exit the cell cycle by growth factor withdrawal, before apoptosis could be evidenced. Results By the Affymetrix microarrays HG-U133 2.0 Plus, 53 genes were distinguished as differentially expressed before and soon after IL-2 deprivation. Among those, PIM1, BCL2, IL-8, HBEGF, DUSP6, OSM, CISH, SOCS2, SOCS3, LIF and IL13 were down-regulated and RPS24, SQSTM1, TMEM1, LRRC8D, ECOP, YY1AP1, C1orf63, ASAH1, SLC25A46 and MIA3 were up-regulated. Genes linked to transcription, cell cycle, cell growth, proliferation and differentiation, cell adhesion, and immune functions were found to be overrepresented within the set of the differentially expressed genes. Conclusion Cell cycle exit of the growth factor-deprived T lymphocytes is characterised by a signature of differentially expressed genes. A coordinate repression of a set of genes known to be induced during T cell activation is observed. However, growth arrest following exit from the cell cycle is actively controlled by several up-regulated genes that enforce the non-dividing state. The identification of genes involved in cell cycle exit and quiescence provides new hints for further studies on the molecular mechanisms regulating the non-dividing state of a cell, the mechanisms closely related to cancer development and to many biological processes.

  15. Molecular epidemiology of human sporotrichosis in Venezuela reveals high frequency of Sporothrix globosa.

    Science.gov (United States)

    Camacho, Emma; León-Navarro, Isabel; Rodríguez-Brito, Sabrina; Mendoza, Mireya; Niño-Vega, Gustavo A

    2015-02-25

    Sporotrichosis is a cutaneous and subcutaneous fungal disease of humans and other mammals, known to be caused by the Sporothrix schenckii species complex, which comprises four species of clinical importance: S. brasiliensis, S. globosa, S. luriei, and S. schenckii sensu stricto. Of them, S. globosa and S. schenckii s. str. show global distribution and differences in global frequency as causal agents of the disease. In the Americas, only three species are present: S. schenckii s. str., S. brasiliensis (so far, only reported in Brazil), and S. globosa. In Venezuela, since the first case of sporotrichosis reported in 1935, S. schenckii have been considered its unique etiological agent. In the present work, the presence of more than one species in the country was evaluated. By phenotypic key features and molecular phylogeny analyses, we re-examined 30 isolates from diverse Venezuelan regions belonging to the fungi collection of Instituto de Biomedicina, Caracas, Venezuela, and national reference center for skin diseases. All isolates were collected between 1973 and 2013, and maintained in distilled water. Sporotrichosis in Venezuela is mainly caused by S. schenckii s. str. (70%). However, a significant proportion (30%) of sporotrichosis cases in the country can be attributable to S. globosa. A correlation between intraspecific genotypes and clinical presentation is proposed. Our data suggest that sporotrichosis various clinical forms might be related to genetic diversity of isolates, and possibly, to diverse virulence profiles previously reported in the S. schenckii species complex. Sporothrix globosa was found to be the causative agent of 30% of sporotrichosis for the Venezuelan cases re-examined, the highest frequency of this species so far reported in the Americas. The high genetic variability presented by S. schenckii s. str. indicates that species distinction based on phenotypic key features could be a challenging and uncertain task; molecular identification

  16. Molecular modeling study for inhibition mechanism of human chymase and its application in inhibitor design.

    Directory of Open Access Journals (Sweden)

    Mahreen Arooj

    Full Text Available Human chymase catalyzes the hydrolysis of peptide bonds. Three chymase inhibitors with very similar chemical structures but highly different inhibitory profiles towards the hydrolase function of chymase were selected with the aim of elucidating the origin of disparities in their biological activities. As a substrate (angiotensin-I bound crystal structure is not available, molecular docking was performed to dock the substrate into the active site. Molecular dynamics simulations of chymase complexes with inhibitors and substrate were performed to calculate the binding orientation of inhibitors and substrate as well as to characterize conformational changes in the active site. The results elucidate details of the 3D chymase structure as well as the importance of K40 in hydrolase function. Binding mode analysis showed that substitution of a heavier Cl atom at the phenyl ring of most active inhibitor produced a great deal of variation in its orientation causing the phosphinate group to interact strongly with residue K40. Dynamics simulations revealed the conformational variation in region of V36-F41 upon substrate and inhibitor binding induced a shift in the location of K40 thus changing its interactions with them. Chymase complexes with the most active compound and substrate were used for development of a hybrid pharmacophore model which was applied in databases screening. Finally, hits which bound well at the active site, exhibited key interactions and favorable electronic properties were identified as possible inhibitors for chymase. This study not only elucidates inhibitory mechanism of chymase inhibitors but also provides key structural insights which will aid in the rational design of novel potent inhibitors of the enzyme. In general, the strategy applied in the current study could be a promising computational approach and may be generally applicable to drug design for other enzymes.

  17. Molecular insight into substrate recognition by human cytosolic sialidase NEU2.

    Science.gov (United States)

    Mozzi, Alessandra; Mazzacuva, Pietro; Zampella, Giuseppe; Forcella, Matilde Emma; Fusi, Paola Alessandra; Monti, Eugenio

    2012-04-01

    Sialidases or neuramidases are glycoside hydrolases removing terminal sialic acid residues from sialo-glycoproteins and sialo-glycolipids. Viral neuraminidases (NAs) have been extensively characterized and represent an excellent target for antiviral therapy through the synthesis of a series of competitive inhibitors that block the release of newly formed viral particles from infected cells. The human cytosolic sialidase NEU2 is the only mammalian enzyme structurally characterized and represents a valuable model to study the specificity of novel NA inhibitory drugs. Moreover, the availability of NEU2 3D structure represents a pivotal step toward the characterization of the molecular basis of natural substrates recognition by the enzyme. In this perspective, we have carried out a study of molecular docking of NEU2 active site using natural substrates of increasing complexity. Moreover, selective mutations of the residues putatively involved into substrate(s) interaction/recognition have been performed, and the resulting mutant enzymes have been preliminary tested for their catalytic activity and substrate specificity. We found that Q270 is involved in the binding of the disaccharide α(2,3) sialyl-galactose, whereas K45 and Q112 bind the distal glucose of the trisaccharide α(2,3) sialyl-lactose, corresponding to the oligosaccharide moiety of GM3 ganglioside. In addition, E218, beside D46, is proved to be a key catalytic residue, being, together with Y334, the second member of the nucleophile pair required for the catalysis. Overall, our results point out the existence of a dynamic network of interactions that are possibly involved in the recognition of the glycans bearing sialic acid. Copyright © 2011 Wiley Periodicals, Inc.

  18. Gene expression correlations in human cancer cell lines define molecular interaction networks for epithelial phenotype.

    Science.gov (United States)

    Kohn, Kurt W; Zeeberg, Barry M; Reinhold, William C; Pommier, Yves

    2014-01-01

    Using gene expression data to enhance our knowledge of control networks relevant to cancer biology and therapy is a challenging but urgent task. Based on the premise that genes that are expressed together in a variety of cell types are likely to functions together, we derived mutually correlated genes that function together in various processes in epithelial-like tumor cells. Expression-correlated genes were derived from data for the NCI-60 human tumor cell lines, as well as data from the Broad Institute's CCLE cell lines. NCI-60 cell lines that selectively expressed a mutually correlated subset of tight junction genes served as a signature for epithelial-like cancer cells. Those signature cell lines served as a seed to derive other correlated genes, many of which had various other epithelial-related functions. Literature survey yielded molecular interaction and function information about those genes, from which molecular interaction maps were assembled. Many of the genes had epithelial functions unrelated to tight junctions, demonstrating that new function categories were elicited. The most highly correlated genes were implicated in the following epithelial functions: interactions at tight junctions (CLDN7, CLDN4, CLDN3, MARVELD3, MARVELD2, TJP3, CGN, CRB3, LLGL2, EPCAM, LNX1); interactions at adherens junctions (CDH1, ADAP1, CAMSAP3); interactions at desmosomes (PPL, PKP3, JUP); transcription regulation of cell-cell junction complexes (GRHL1 and 2); epithelial RNA splicing regulators (ESRP1 and 2); epithelial vesicle traffic (RAB25, EPN3, GRHL2, EHF, ADAP1, MYO5B); epithelial Ca(+2) signaling (ATP2C2, S100A14, BSPRY); terminal differentiation of epithelial cells (OVOL1 and 2, ST14, PRSS8, SPINT1 and 2); maintenance of apico-basal polarity (RAB25, LLGL2, EPN3). The findings provide a foundation for future studies to elucidate the functions of regulatory networks specific to epithelial-like cancer cells and to probe for anti-cancer drug targets.

  19. Molecular epidemiology of Mycobacterium tuberculosis in Baja California, Mexico: A result of human migration?

    Science.gov (United States)

    Flores-López, Carlos A; Zenteno-Cuevas, Roberto; Laniado-Laborín, Rafael; Reynaud, Yann; García-Ortiz, Rosa Alejandra; González-Y-Merchand, Jorge A; Rivera, Sandra; Vázquez-Chacón, Carlos A; Vaughan, Gilberto; Martínez-Guarneros, José Armando; Victoria-Cota, Nelva Lorena; Cruz-Rivera, Mayra; Rastogi, Nalin; Muñiz-Salazar, Raquel

    2017-11-01

    The State of Baja California (BC) exhibits the highest incidence and prevalence rates of tuberculosis (TB), and multidrug-resistant TB (MDR-TB) in Mexico. However information about the circulation of M. tuberculosis lineages in BC and Mexico as a whole is limited. Here, we describe the genetic relationship and genetic diversity among M. tuberculosis clinical isolates (n=140) collected in BC between October 2009 and April 2011 with other regions of Mexico, the United States, and Latin America. All specimens were genotyped based on 24 mycobacterial interspersed repetitive units (MIRU)-variable number of tandem repeats (VNTR) loci. Population structure and minimum spanning tree (MST) analyses were used to assess the genetic diversity and distribution of BC isolates in comparison to USA and South America strains. Among the nine lineages observed, LAM, Haarlem and S were the most frequent identified in BC. Population structure analysis clustered most BC isolates (41%) into three distinctive groups that included strains from San Diego and South America, whereas other BC strains (22%) clustered with other Mexican strains. A subset of isolates (12%) seemed to be autochthonous of BC, while 25% were cosmopolitan and grouped into multiple clusters. It is highly likely that the TB genetic structure observed in BC is due to human migration. Additional studies are required to determine the mechanism involved in the phylogeographic distribution of M. tuberculosis in Mexico. Implementation of domestic molecular TB surveillance programs is required to better understand the molecular epidemiology of TB not only in the region but at the national level. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Conjugated linoleic acid enhances transepithelial calcium transport in human intestinal-like Caco-2 cells: An insight into molecular changes

    NARCIS (Netherlands)

    Murphy, E.F.; Jewell, C.; Hooiveld, G.J.E.J.; Müller, M.R.; Cashman, K.D.

    2006-01-01

    Conjugated linoleic acid (CLA) has been shown to enhance paracellular and transcellular Ca transport across human intestinal-like Caco-2 cell monolayers. The mechanisms of action, however, are still unclear. Therefore, this study investigated the molecular mechanisms underlying CLA-induced

  1. Molecular basis of retinol anti-ageing properties in naturally aged human skin in vivo.

    Science.gov (United States)

    Shao, Y; He, T; Fisher, G J; Voorhees, J J; Quan, T

    2017-02-01

    Retinoic acid has been shown to improve the aged-appearing skin. However, less is known about the anti-ageing effects of retinol (ROL, vitamin A), a precursor of retinoic acid, in aged human skin in vivo. This study aimed to investigate the molecular basis of ROL anti-ageing properties in naturally aged human skin in vivo. Sun-protected buttock skin (76 ± 6 years old, n = 12) was topically treated with 0.4% ROL and its vehicle for 7 days. The effects of topical ROL on skin epidermis and dermis were evaluated by immunohistochemistry, in situ hybridization, Northern analysis, real-time RT-PCR and Western analysis. Collagen fibrils nanoscale structure and surface topology were analysed by atomic force microscopy. Topical ROL shows remarkable anti-ageing effects through three major types of skin cells: epidermal keratinocytes, dermal endothelial cells and fibroblasts. Topical ROL significantly increased epidermal thickness by stimulating keratinocytes proliferation and upregulation of c-Jun transcription factor. In addition to epidermal changes, topical ROL significantly improved dermal extracellular matrix (ECM) microenvironment; increasing dermal vascularity by stimulating endothelial cells proliferation and ECM production (type I collagen, fibronectin and elastin) by activating dermal fibroblasts. Topical ROL also stimulates TGF-β/CTGF pathway, the major regulator of ECM homeostasis, and thus enriched the deposition of ECM in aged human skin in vivo. 0.4% topical ROL achieved similar results as seen with topical retinoic acid, the biologically active form of ROL, without causing noticeable signs of retinoid side effects. 0.4% topical ROL shows remarkable anti-ageing effects through improvement of the homeostasis of epidermis and dermis by stimulating the proliferation of keratinocytes and endothelial cells, and activating dermal fibroblasts. These data provide evidence that 0.4% topical ROL is a promising and safe treatment to improve the naturally aged human skin

  2. Multiple Adaptive Neuro-Fuzzy Inference System with Automatic Features Extraction Algorithm for Cervical Cancer Recognition

    Directory of Open Access Journals (Sweden)

    Mohammad Subhi Al-batah

    2014-01-01

    Full Text Available To date, cancer of uterine cervix is still a leading cause of cancer-related deaths in women worldwide. The current methods (i.e., Pap smear and liquid-based cytology (LBC to screen for cervical cancer are time-consuming and dependent on the skill of the cytopathologist and thus are rather subjective. Therefore, this paper presents an intelligent computer vision system to assist pathologists in overcoming these problems and, consequently, produce more accurate results. The developed system consists of two stages. In the first stage, the automatic features extraction (AFE algorithm is performed. In the second stage, a neuro-fuzzy model called multiple adaptive neuro-fuzzy inference system (MANFIS is proposed for recognition process. The MANFIS contains a set of ANFIS models which are arranged in parallel combination to produce a model with multi-input-multioutput structure. The system is capable of classifying cervical cell image into three groups, namely, normal, low-grade squamous intraepithelial lesion (LSIL and high-grade squamous intraepithelial lesion (HSIL. The experimental results prove the capability of the AFE algorithm to be as effective as the manual extraction by human experts, while the proposed MANFIS produces a good classification performance with 94.2% accuracy.

  3. Multiple adaptive neuro-fuzzy inference system with automatic features extraction algorithm for cervical cancer recognition.

    Science.gov (United States)

    Al-batah, Mohammad Subhi; Isa, Nor Ashidi Mat; Klaib, Mohammad Fadel; Al-Betar, Mohammed Azmi

    2014-01-01

    To date, cancer of uterine cervix is still a leading cause of cancer-related deaths in women worldwide. The current methods (i.e., Pap smear and liquid-based cytology (LBC)) to screen for cervical cancer are time-consuming and dependent on the skill of the cytopathologist and thus are rather subjective. Therefore, this paper presents an intelligent computer vision system to assist pathologists in overcoming these problems and, consequently, produce more accurate results. The developed system consists of two stages. In the first stage, the automatic features extraction (AFE) algorithm is performed. In the second stage, a neuro-fuzzy model called multiple adaptive neuro-fuzzy inference system (MANFIS) is proposed for recognition process. The MANFIS contains a set of ANFIS models which are arranged in parallel combination to produce a model with multi-input-multioutput structure. The system is capable of classifying cervical cell image into three groups, namely, normal, low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL). The experimental results prove the capability of the AFE algorithm to be as effective as the manual extraction by human experts, while the proposed MANFIS produces a good classification performance with 94.2% accuracy.

  4. Asynchronous neuro-osseous growth in adolescent idiopathic scoliosis - MRI-based research

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Winnie C.W.; Rasalkar, Darshana D. [The Chinese University of Hong Kong, Department of Diagnostic Radiology and Organ Imaging, Hong Kong, SAR (China); Cheng, Jack C.Y. [The Chinese University of Hong Kong, Department of Orthopaedics and Traumatology, Hong Kong, SAR (China)

    2011-09-15

    Adolescent idiopathic scoliosis (AIS) is a common worldwide problem and has been treated for many decades; however, there still remain uncertain areas about this disorder. Its involvement and impact on different parts of the human body remain underestimated due to lack of technology in imaging for objective assessment in the past. The advances in imaging technique and image analysis technology have provided a novel approach for the understanding of the phenotypic presentation of neuro-osseous changes in AIS patients as compared with normal controls. This review is the summary of morphological assessment of the skeletal and nervous systems in girls with AIS based on MRI. Girls with AIS are found to have morphological differences in multiple areas including the vertebral column, spinal cord, skull and brain when compared with age- and sex-matched normal controls. Taken together, the abnormalities in the skeletal system and nervous system of AIS are likely to be inter-related and reflect a systemic process of asynchronous neuro-osseous growth. The current knowledge about the anatomical changes in AIS has important implications with respect to the understanding of fundamental pathomechanical processes involved in the evolution of the scoliotic deformity. (orig.)

  5. Generative NeuroEvolution for Deep Learning

    OpenAIRE

    Verbancsics, Phillip; Harguess, Josh

    2013-01-01

    An important goal for the machine learning (ML) community is to create approaches that can learn solutions with human-level capability. One domain where humans have held a significant advantage is visual processing. A significant approach to addressing this gap has been machine learning approaches that are inspired from the natural systems, such as artificial neural networks (ANNs), evolutionary computation (EC), and generative and developmental systems (GDS). Research into deep learning has ...

  6. Analyzing the dynamics of emotional scene sequence using recurrent neuro-fuzzy network.

    Science.gov (United States)

    Zhang, Qing; Lee, Minho

    2013-02-01

    In this paper, we propose a new framework to analyze the temporal dynamics of the emotional stimuli. For this framework, both electroencephalography signal and visual information are of great importance. The fusion of visual information with brain signals allows us to capture the users' emotional state. Thus we adopt previously proposed fuzzy-GIST as emotional feature to summarize the emotional feedback. In order to model the dynamics of the emotional stimuli sequence, we develop a recurrent neuro-fuzzy network for modeling the dynamic events of emotional dimensions including valence and arousal. It can incorporate human expertise by IF-THEN fuzzy rule while recurrent connections allow the fuzzy rules of network to see its own previous output. The results show that such a framework can interact with human subjects and generate arbitrary emotional sequences after learning the dynamics of an emotional sequence with enough number of samples.

  7. Attack, parry and riposte: molecular fencing between the innate immune system and human herpesviruses.

    Science.gov (United States)

    Le-Trilling, V T K; Trilling, M

    2015-07-01

    Once individuals acquire one of the eight human-pathogenic herpesviruses, the upcoming relationship is predefined to last lifelong. Despite the fact that acute phases of herpesviral replication are usually confined and controlled by a concerted action of all branches of the healthy immune system, sterile immunity is never reached. To accomplish this, herpesviruses evolved the unique ability to outlast episodes of efficient immunity in a dormant state called latency and a remarkable array of immune antagonists which counteract most (if not all) relevant aspects of intrinsic, innate and adaptive immune responses. Certain psychological and physiological conditions (such as stress, immuno-suppression or pregnancy) predispose for viral reactivation which can lead to recurrent disease and virus spread. One important pillar of immunity is the innate immune system. The leading cytokines of the innate immune response are interferons (IFN). IFNs reinforce intrinsic immunity, induce a cell-intrinsic antiviral state and recruit and orchestrate adaptive immunity. Consistently, individuals lacking a functional IFN system suffer from otherwise harmless opportunists and live-attenuated vaccines. The selective pressure elicited by IFNs drove herpesviruses to evolve numerous IFN antagonistic gene products. A molecular in-depth understanding of (herpes-) viral IFN antagonists might allow the design of novel antiviral drugs which reconstitute IFN responses by blocking the antagonistic function and thereby help the host to help himself. Additionally, virus mutants lacking immune evasins constitute promising candidates for vaccine viruses. Here we summarize the current knowledge on IFN antagonistic strategies of the eight human herpesviruses and try to decipher common strategies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Insights from Analysis of Binding Sites of Human Meprins: Screening of Inhibitors by Molecular Dynamics Simulation Study.

    Science.gov (United States)

    Chaudhuri, Ankur; Bera, Asim K; Sarkar, Indrani; Chakraborty, Sibani

    2016-01-01

    Human meprin-α and-β are important regulators of angiogenesis, cancer, inflammation, fibrosis, and neurodegenerative diseases and hence important therapeutic targets. Meprins are the only astacin proteases that are expressed in membrane-bound and secreted form. The cleavage specificity of human meprins is similar in certain cases but differs markedly in others. The inhibitor selectivity of human meprins is controlled by the specific residues involved in binding at the active-site cleft of the proteases. Meprins are inhibited by various small molecular inhibitors as well as macromolecular endogenous inhibitors, making them good drug targets. In the current study, molecular dynamics simulation was performed for 10 ns on ten systems consisting of two apoenzymes of meprin -α/β and eight complexes of human meprin-α and -β complexed to four inhibitors with different metal binding moieties and comparable Ki values. These simulation studies helped to elucidate the molecular details of how several parameters influence protein-inhibitor binding affinity. Analysis of the interaction energies of the protein-inhibitor complexes revealed the diverse binding nature of this series of inhibitors. Several structural segments of human meprins exhibited certain conformational changes during the simulation time course. Among the inhibitors studied captopril had a different disposition in the meprin-bound complexes compared to the other three inhibitors, namely Pro- Leu-Gly-hydroxamate, galardin and EDTA. Comparison of the interaction energies for each system helped us to conclude that the hydroxamic acid-based inhibitors are the most potent inhibitors of meprins.

  9. Molecular Mechanisms of Malignant Transformation by Low Dose Cadmium in Normal Human Bronchial Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Laura Cartularo

    Full Text Available Cadmium is a carcinogenic metal, the mechanisms of which are not fully understood. In this study, human bronchial epithelial cells were transformed with sub-toxic doses of cadmium (0.01, 0.05, and 0.1 μM and transformed clones were characterized for gene expression changes using RNA-seq, as well as other molecular measurements. 440 genes were upregulated and 47 genes were downregulated in cadmium clones relative to control clones over 1.25-fold. Upregulated genes were associated mostly with gene ontology terms related to embryonic development, immune response, and cell movement, while downregulated genes were associated with RNA metabolism and regulation of transcription. Several embryonic genes were upregulated, including the transcription regulator SATB2. SATB2 is critical for normal skeletal development and has roles in gene expression regulation and chromatin remodeling. Small hairpin RNA knockdown of SATB2 significantly inhibited growth in soft agar, indicating its potential as a driver of metal-induced carcinogenesis. An increase in oxidative stress and autophagy was observed in cadmium clones. In addition, the DNA repair protein O6-methylguanine-DNA-methyltransferase was depleted by transformation with cadmium. MGMT loss caused significant decrease in cell viability after treatment with the alkylating agent temozolomide, demonstrating diminished capacity to repair such damage. Results reveal various mechanisms of cadmium-induced malignant transformation in BEAS-2B cells including upregulation of SATB2, downregulation of MGMT, and increased oxidative stress.

  10. Molecular epidemiology of human enterovirus associated with aseptic meningitis in Shandong Province, China, 2006-2012.

    Science.gov (United States)

    Tao, Zexin; Wang, Haiyan; Li, Yan; Liu, Guifang; Xu, Aiqiang; Lin, Xiaojuan; Song, Lizhi; Ji, Feng; Wang, Suting; Cui, Ning; Song, Yanyan

    2014-01-01

    Human enteroviruses (HEVs) are common causes of acute meningitis. However, there is limited information about HEV associated with aseptic meningitis in mainland China because it has not been classified as a notifiable disease. To characterize the HEVs associated with sporadic aseptic meningitis in China and to analyze their genetic features. Cerebrospinal fluid, throat swab and feces specimens were collected from patients with aseptic meningitis in 5 sentinel hospitals in Shandong Province, China between 2006 and 2012. Virological investigation (viral isolation and molecular identification) and phylogenetic analysis were performed. A total of 437 hospitalized patients were reported, and enteroviruses were detected in the specimens from 84 patients (19.2%) and were identified into 17 serotypes. The nine main serotypes were echovirus (E) 30 (27.4%), EV71 (13.1%), coxsackievirus (CV) B1 (9.5%), CVB3 (7.1%), CVB5 (7.1%), E6 (7.1%), E9 (7.1%), CVA9 (6.0%), and CVA10 (3.6%). Monthly distribution of isolated enteroviruses revealed a major peak in summer-fall season and a small second peak in winter constituted totally by EV71. Sequence analysis on VP1 coding region suggested Shandong strains had great genetic divergence with isolates from other countries. Multiple serotypes were responsible for enterovirus meningitis in mainland China. Aseptic meningitis caused by EV71 and coxsackie A viruses-the predominant pathogens for the hand, foot, and mouth disease-is currently an important concern in mainland China.

  11. Cellular and molecular portrait of eleven human glioblastoma cell lines under photon and carbon ion irradiation.

    Science.gov (United States)

    Ferrandon, S; Magné, N; Battiston-Montagne, P; Hau-Desbat, N-H; Diaz, O; Beuve, M; Constanzo, J; Chargari, C; Poncet, D; Chautard, E; Ardail, D; Alphonse, G; Rodriguez-Lafrasse, C

    2015-04-28

    This study aimed to examine the cellular and molecular long-term responses of glioblastomas to radiotherapy and hadrontherapy in order to better understand the biological effects of carbon beams in cancer treatment. Eleven human glioblastoma cell lines, displaying gradual radiosensitivity, were irradiated with photons or carbon ions. Independently of p53 or O(6)-methylguanine-DNA methyltransferase(1) status, all cell lines responded to irradiation by a G2/M phase arrest followed by the appearance of mitotic catastrophe, which was concluded by a ceramide-dependent-apoptotic cell death. Statistical analysis demonstrated that: (i) the SF2(2) and the D10(3) values for photon are correlated with that obtained in response to carbon ions; (ii) regardless of the p53, MGMT status, and radiosensitivity, the release of ceramide is associated with the induction of late apoptosis; and (iii) the appearance of polyploid cells after photon irradiation could predict the Relative Biological Efficiency(4) to carbon ions. This large collection of data should increase our knowledge in glioblastoma radiobiology in order to better understand, and to later individualize, appropriate radiotherapy treatment for patients who are good candidates. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Mining the human genome after Association for Molecular Pathology v. Myriad Genetics.

    Science.gov (United States)

    Evans, Barbara J

    2014-07-01

    The Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics portrays the human genome as a product of nature. This frames medical genetics as an extractive industry that mines a natural resource to produce valuable goods and services. Natural resource law offers insights into problems medical geneticists can expect after this decision and suggests possible solutions. Increased competition among clinical laboratories offers various benefits but threatens to increase fragmentation of genetic data resources, potentially causing waste in the form of lost opportunities to discover the clinical significance of particular gene variants. The solution lies in addressing legal barriers to appropriate data sharing. Sustainable discovery in the field of medical genetics can best be achieved through voluntary data sharing rather than command-and-control tactics, but voluntary mechanisms must be conceived broadly to include market-based approaches as well as donative and publicly funded data commons. The recently revised Health Insurance Portability and Accountability Act Privacy Rule offers an improved--but still imperfect--framework for market-oriented data sharing. This article explores strategies for addressing the Privacy Rule's remaining defects. America is close to having a legal framework that can reward innovators, protect privacy, and promote needed data sharing to advance medical genetics.

  13. [The problem of molecular-genetic identification of sweat and grease deposits in the human fingerprints].

    Science.gov (United States)

    Faleeva, T G; Ivanov, I N; Mishin, E S; Vnukova, N V; Kornienko, I V

    2016-01-01

    The objective of the present experimental molecular-genetic study of DNA contained in of human fingerprints was to establish the relationship between the reference genetic profiles and the genotypes of the individuals leaving their fingerprints on a smooth metal object. The biological material for the purpose of the investigation was sampled at different time intervals. The were taken using a scotch tape and used to obtain the complete genetic profile immediately after the fingerprints had been left as well as within the next 24 hours and one week. It proved impossible to identify the complete genetic profile one month after the fingerprints had been left. The alleles not typical for reference samples were identified within one week after swabbing the material from the metal surface. The results of the sudy can be explained by the decrease of the concentration of the initial DNA-matrix in the samples due to its degradation in the course of time. It is concluded that the parallel genetic analysis is needed if reliable evidence of identity of the profiles of interest or its absence is to be obtained.

  14. Molecular evidence of high-risk human papillomavirus infection in colorectal tumours from Cuban patients

    Directory of Open Access Journals (Sweden)

    Yudira Soto

    Full Text Available The association between colorectal cancer and human papillomavirus (HPV infection is still unproven. The aim of this study was to investigate the presence of high-risk HPV (HR-HPV DNA in colorectal tissues from Cuban patients. A total of 63 colorectal formalin-fixed paraffin-embedded tissues were studied (24 adenocarcinoma, 18 adenoma, and 21 colorectal tissues classified as benign colitis. DNA from colorectal samples was analysed by quantitative real-time polymerase chain reaction to detect the most clinically relevant high HR-HPV types (HPV-16, -18, -31, -33, -45, -52, and -58. Associations between histologic findings and other risk factors were also analysed. Overall, HPV DNA was detected in 23.8% (15/63 of the samples studied. Viral infections were detected in 41.7% of adenocarcinoma (10/24 and 27.7% of adenoma cases (5/18. HPV DNA was not found in any of the negative cases. An association between histological diagnosis of adenocarcinoma and HPV infection was observed (odd ratio = 4.85, 95% confidence interval = 1.40-16.80, p = 0.009. The only genotypes identified were HPV 16 and 33. Viral loads were higher in adenocarcinoma, and these cases were associated with HPV 16. This study provides molecular evidence of HR-HPV infection in colorectal adenocarcinoma tissues from Cuban patients.

  15. Molecular characterization of human respiratory syncytial virus detected from central India.

    Science.gov (United States)

    Sahu, Mahima; Shukla, Mohan K; Barde, Pradip V

    2017-10-01

    Human Respiratory syncytial virus (hRSV) is the major cause of respiratory tract infection in both children and adults, virtually all children acquire infection with hRSV by the age of 3 years. Two subgroups of the virus, hRSV-A and hRSV-B based on sequence variability of G protein gene are divided into 11 and 17 genotypes, respectively. Very limited data regarding circulating genotypes is available from India. This study aimed to detect and characterize the circulating genotype of hRSV from central India. Throat swabs collected from patient's having influenza like illness (ILI) were subjected to RT-PCR for diagnosis, further sequencing and phylogenetic analysis was performed using primers specific for C-terminal end of G gene. Out of 526 tested samples 62 (12%) were found positive, 90% cases were from children under 3-year age children. Both hRSV-A and hRSV-B were detected in equal proportions. Sequence analysis of 15 samples revealed circulation of genotypes NA1, ON1 of hRSV-A, and BA9 of hRSV-B. We advocate molecular surveillance of hRSV for better patient management and epidemiological monitoring. © 2017 Wiley Periodicals, Inc.

  16. Identification of prognostic molecular features in the reactive stroma of human breast and prostate cancer.

    Directory of Open Access Journals (Sweden)

    Anne Planche

    Full Text Available Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value.

  17. Molecular Recognition of Human Liver Cancer Cells Using DNA Aptamers Generated via Cell-SELEX.

    Directory of Open Access Journals (Sweden)

    Jiehua Xu

    Full Text Available Most clinical cases of liver cancer cannot be diagnosed until they have evolved to an advanced stage, thus resulting in high mortality. It is well recognized that the implementation of early detection methods and the development of targeted therapies for liver cancer are essential to reducing the high mortality rates associated with this disease. To achieve these goals, molecular probes capable of recognizing liver cancer cell-specific targets are needed. Here we describe a panel of aptamers able to distinguish hepatocarcinoma from normal liver cells. The aptamers, which were selected by cell-based SELEX (Systematic Evolution of Ligands by Exponential Enrichment, have Kd values in the range of 64-349 nM toward the target human hepatoma cell HepG2, and also recognize ovarian cancer cells and lung adenocarcinoma. The proteinase treatment experiment indicated that all aptamers could recognize target HepG2 cells through surface proteins. This outcome suggested that these aptamers could be used as potential probes for further research in cancer studies, such as developing early detection assays, targeted therapies, and imaging agents, as well as for the investigation of common membrane proteins in these distinguishable cancers.

  18. Molecular mechanisms of resveratrol-induced apoptosis in human pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Napaporn Kaewdoungdee

    2014-10-01

    Full Text Available Resveratrol is a polyphenolic phytoalexin found at high concentrations in grapes, nuts, fruits and red wine with reported anti -carcinogenic effects. In this study, the molecular mechanism of resveratrol -induced apoptosis in human pancreatic cancer (Panc 2.03 cells is investigated. Resveratrol treatment of Panc 2.03 cells results in dose-dependent inhibition of cell growth and cells accumulated at the S phase transition of the cell cycle. The anti -proliferative effect of resveratrol is due to apoptosis as seen by the appearance of chrom atin condensation, nuclear fragmentation, DNA ladder formation and increased annexin V-stained cells. The apoptotic process is induced by decreased Bcl-2 expression concomitant with increased Bax expression, leading to an increase in the Bax/Bcl-2 ratio and subsequent activation of caspase-9 and caspase-3. In addition, resveratrol treatment also decreases the survivin level and increases the apoptosis-inducing factor level in a dose-dependent manner. These results suggest that resveratrol induces apoptosis of Panc 2.03 cells, at least in part through a mitochondrial -associated intrinsic pathway in both caspasedependent and independent manners. The present findings suggest that resveratrol has potential as a chemopreventive agent, and possibly as a therapeutic one against pancreatic cancer.

  19. Low molecular weight heparin and aspirin exacerbate human endometrial endothelial cell responses to antiphospholipid antibodies.

    Science.gov (United States)

    Quao, Zola Chihombori; Tong, Mancy; Bryce, Elena; Guller, Seth; Chamley, Lawrence W; Abrahams, Vikki M

    2018-01-01

    Women with antiphospholipid antibodies (aPL) are at risk for pregnancy complications despite treatment with low molecular weight heparin (LMWH) or aspirin (ASA). aPL recognizing beta2 glycoprotein I can target the uterine endothelium, however, little is known about its response to aPL. This study characterized the effect of aPL on human endometrial endothelial cells (HEECs), and the influence of LMWH and ASA. HEECs were exposed to aPL or control IgG, with or without low-dose LMWH and ASA, alone or in combination. Chemokine and angiogenic factor secretion were measured by ELISA. A tube formation assay was used to measure angiogenesis. aPL increased HEEC secretion of pro-angiogenic VEGF and PlGF; increased anti-angiogenic sFlt-1; inhibited basal secretion of the chemokines MCP-1, G-CSF, and GRO-α; and impaired angiogenesis. LMWH and ASA, alone and in combination, exacerbated the aPL-induced changes in the HEEC angiogenic factor and chemokine profile. There was no reversal of the aPL inhibition of HEEC angiogenesis by either single or combination therapy. By aPL inhibiting HEEC chemokine secretion and promoting sFlt-1 release, the uterine endothelium may contribute to impaired placentation and vascular transformation. LMWH and ASA may further contribute to endothelium dysfunction in women with obstetric APS. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Molecular dynamics simulation of the thermosensitivity of the human connexin 26 hemichannel

    Science.gov (United States)

    Alizadeh, Hadi; Davoodi, Jamal; Zeilinger, Carsten; Rafii-Tabar, Hashem

    2018-01-01

    Connexin hemichannels mediate cytoplasm and extracellular milieu communication by exchanging a variety of cytoplasmic molecules and ions. These hemichannels can be regulated by external stimuli such as mechanical stress, applied voltage, pH and temperature changes. Although there are many studies on structures and functions of connexin 26 in contexts of pH, ion concentration and voltage, employing computational methods, no such study has been performed so far involving temperature changes. In this study, using molecular dynamics simulation, we investigate thermosensitivity of the human Connexin 26 hemichannel. Our results show that the channel approaches a structurally closed state at lower temperature compared to higher temperature. This is in fair agreement with experimental results that indicate channel closure at lower temperature. Furthermore, our MD simulation results show that some regions of connexin 26 hemichannel are more sensitive to temperature compared to other regions. Whereas the intercellular half of the channel does not show any considerable response to temperature during the simulation time accessible in this study, the cytoplasmic half approaches a closed structural state at lower temperature compared to the higher temperature. Specifically, our results suggest that the cytoplasmic loop, the cytoplasmic half of the second transmembrane helix, and the N-terminus helix play a dominant role in temperature gating.

  1. Three low molecular weight cysteine proteinase inhibitors of human seminal fluid: purification and enzyme kinetic properties.

    Science.gov (United States)

    Yadav, Vikash Kumar; Chhikara, Nirmal; Gill, Kamaldeep; Dey, Sharmistha; Singh, Sarman; Yadav, Savita

    2013-08-01

    The cystatins form a superfamily of structurally related proteins with highly conserved structural folds. They are all potent, reversible, competitive inhibitors of cysteine proteinases (CPs). Proteins from this group present differences in proteinase inhibition despite their high level of structural similarities. In this study, three cysteine proteinase inhibitors (CPIs) of low molecular weight were isolated from human seminal fluid (HSF) by affinity chromatography on carboxymethyl (CM)-papain-Sepharose column, purified using various chromatographic procedures and checked for purity on sodium-dodecyl PAGE (SDS-PAGE). Matrix-assisted laser desorption-ionization-time-of flight-mass spectrometry (MALDI-TOF-MS) identified these proteins as cystatin 9, cystatin SN, and SAP-1 (an N-terminal truncated form of cystatin S). All three CPIs suppressed the activity of papain potentially and showed remarkable heat stability. Interestingly SAP-1 also inhibits the activity of trypsin, chymotrypsin, pepsin, and PSA (prostate specific antigen) and acts as a cross-class protease inhibitor in in vitro studies. Using Surface Plasmon Resonance, we have also observed that SAP-1 shows a significant binding with all these proteases. These studies suggest that SAP-1 is a cross-class inhibitor that may regulate activity of various classes of proteases within the reproductive systems. To our knowledge, this is the first report about purification of CPIs from HSF; the identification of such proteins could provide better insights into the physiological processes and offer intimation for further research. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  2. DETECTION OF OXIDATIVE STRESS, APOPTOSIS AND MOLECULAR LESIONS IN HUMAN OVARIAN CANCER CELLS

    Directory of Open Access Journals (Sweden)

    H. I. Falfushynska

    2016-05-01

    Full Text Available Background. Ovarian cancer has the highest mortality rate of gynaecological cancers. This is partly due to the lack of effective screening markers. Indices of oxidative stress are well-recognized prognostic criteria for tumorous transformation of tissue, but their value depends on the type of tumor and the stage of its development. Objective. The aim of this study is to clarify the relationship between antioxidant/pro-oxidant ratio and the signs of molecular lesions and apoptosis rate in blood of ovarian cancer patients and non-cancer ones. Results. The ovarian cancer group is marked by antioxidant/prooxidant balance shifting to oxidative damage in blood as the consequence of overexpression of oxyradicals (by 300%. Higher level of glutathione (by 366%, lower level of metallothioneins (by 65% as well as higher level of lipid peroxidation (by 174% and protein carbonyls (by 186% in blood of ovarian cancer patients compared to the normal ovarian group have been observed. The signs of cytotoxicity are determined in blood of ovarian cancer patients: an increased (compared to control level of DNA fragmentation (by 160%, choline esterase (up to twice, higher rate of both caspase dependent and caspase independent lysosomal mediated apoptosis. Conclusions. Cathepsin D activity both total and free, choline esterase activity, TBA-reactive substance and protein carbonyls level in blood could be used as the predictive markers of worse prognosis and the signs of human ovarian cancer.

  3. Integrative molecular phylogeography in the context of infectious diseases on the human-animal interface.

    Science.gov (United States)

    Gray, Rebecca R; Salemi, Marco

    2012-12-01

    The rate of new emerging infectious diseases entering the human population has increased over the past century, with pathogens originating from animals or from products of animal origin accounting for the vast majority. Primary risk factors for the emergence and spread of emerging zoonoses include expansion and intensification of animal agriculture and long-distance live animal transport, live animal markets, bushmeat consumption and habitat destruction. Developing effective control strategies is contingent upon the ability to test causative hypotheses of disease transmission within a statistical framework. Broadly speaking, molecular phylogeography offers a framework in which specific hypotheses regarding pathogen gene flow and dispersal within an ecological context can be compared. A number of different methods has been developed for this application. Here, our intent is firstly to discuss the application of a wide variety of statistically based methods (including Bayesian reconstruction, network parsimony analysis and regression) to specific viruses (influenza, salmon anaemia virus, foot and mouth disease and Rift Valley Fever) that have been associated with animal farming/movements; and secondly to place them in the larger framework of the threat of potential zoonotic events as well as the economic and biosecurity implications of pathogen outbreaks among our animal food sources.

  4. Merkel Cell Polyomavirus: Molecular Insights into the Most Recently Discovered Human Tumour Virus

    Energy Technology Data Exchange (ETDEWEB)

    Stakaitytė, Gabrielė; Wood, Jennifer J.; Knight, Laura M.; Abdul-Sada, Hussein; Adzahar, Noor Suhana; Nwogu, Nnenna; Macdonald, Andrew; Whitehouse, Adrian, E-mail: A.Whitehouse@leeds.ac.uk [School of Molecular and Cellular Biology and Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT (United Kingdom)

    2014-06-27

    A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV) was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC.

  5. Spontaneous quaternary and tertiary T-R transitions of human hemoglobin in molecular dynamics simulation.

    Directory of Open Access Journals (Sweden)

    Jochen S Hub

    2010-05-01

    Full Text Available We present molecular dynamics simulations of unliganded human hemoglobin (Hb A under physiological conditions, starting from the R, R2, and T state. The simulations were carried out with protonated and deprotonated HC3 histidines His(beta146, and they sum up to a total length of 5.6 micros. We observe spontaneous and reproducible T-->R quaternary transitions of the Hb tetramer and tertiary transitions of the alpha and beta subunits, as detected from principal component projections, from an RMSD measure, and from rigid body rotation analysis. The simulations reveal a marked asymmetry between the alpha and beta subunits. Using the mutual information as correlation measure, we find that the beta subunits are substantially more strongly linked to the quaternary transition than the alpha subunits. In addition, the tertiary populations of the alpha and beta subunits differ substantially, with the beta subunits showing a tendency towards R, and the alpha subunits showing a tendency towards T. Based on the simulation results, we present a transition pathway for coupled quaternary and tertiary transitions between the R and T conformations of Hb.

  6. Colocalization of coregulated genes: a steered molecular dynamics study of human chromosome 19.

    Directory of Open Access Journals (Sweden)

    Marco Di Stefano

    Full Text Available The connection between chromatin nuclear organization and gene activity is vividly illustrated by the observation that transcriptional coregulation of certain genes appears to be directly influenced by their spatial proximity. This fact poses the more general question of whether it is at all feasible that the numerous genes that are coregulated on a given chromosome, especially those at large genomic distances, might become proximate inside the nucleus. This problem is studied here using steered molecular dynamics simulations in order to enforce the colocalization of thousands of knowledge-based gene sequences on a model for the gene-rich human chromosome 19. Remarkably, it is found that most (≈ 88% gene pairs can be brought simultaneously into contact. This is made possible by the low degree of intra-chromosome entanglement and the large number of cliques in the gene coregulatory network. A clique is a set of genes coregulated all together as a group. The constrained conformations for the model chromosome 19 are further shown to be organized in spatial macrodomains that are similar to those inferred from recent HiC measurements. The findings indicate that gene coregulation and colocalization are largely compatible and that this relationship can be exploited to draft the overall spatial organization of the chromosome in vivo. The more general validity and implications of these findings could be investigated by applying to other eukaryotic chromosomes the general and transferable computational strategy introduced here.

  7. Molecular cloning, expression, and chromosomal localization of the gene encoding a human myeloid membrane antigen (gp150).

    Science.gov (United States)

    Look, A T; Peiper, S C; Rebentisch, M B; Ashmun, R A; Roussel, M F; Lemons, R S; Le Beau, M M; Rubin, C M; Sherr, C J

    1986-10-01

    DNA from a tertiary mouse cell transformant containing amplified human sequences encoding a human myeloid membrane glycoprotein, gp150, was used to construct a bacteriophage lambda library. A single recombinant phage containing 12 kilobases (kb) of human DNA was isolated, and molecular subclones were then used to isolate the complete gp150 gene from a human placental genomic DNA library. The intact gp150 gene, assembled from three recombinant phages, proved to be biologically active when transfected into NIH 3T3 cells. Molecular probes from the gp150 locus annealed with a 4.0-kb polyadenylated RNA transcript derived from human myeloid cell lines and from tertiary mouse cell transformants. The gp150 gene was assigned to human chromosome 15, and was subchromosomally localized to bands q25-26 by in situ hybridization. The chromosomal location of the gp150 gene coincides cytogenetically with the region assigned to the c-fes proto-oncogene, another human gene specifically expressed by myeloid cells.

  8. Animal welfare: neuro-cognitive approaches

    Directory of Open Access Journals (Sweden)

    Massimo Morgante

    2010-01-01

    Full Text Available Many people maintain a naive belief that non-human animals consciously experience pain and suffering in similar ways to humans. Others tend to assume a more sceptical or agnostic attitude. Drawing on recent advances in research on animal cognition and neuroscience, the science of animal welfare is now beginning to address these issues empirically. We describe recent advances that may contribute to the main questions of animal welfare, namely whether animals are conscious and how we can assess good and bad welfare in animals. Evidence from psychology is described which demonstrate that many complex actions in humans can be carried out quite unconsciously and that human patients with certain sorts of brain damage can behave and manipulate objects properly while at the same time o consciously denying experience of them. The relevance of these findings with respect to the issue of animal consciousness is discussed. Evidence from animal cognition is described concerning the possibility that animals monitor the state of their own memories, show episodic-like knowledge and exhibit self-medication. Evidence from neuroscience concerning brain lateralization in non-human animals and its relevance to animal welfare is described. It is argued that in animals raised for economic purposes (milk and meat production differences in cognitive abilities and brain lateralization can affect adaptive behavioural, physiological and immune responses to environmental stressors.

  9. Molecular characteristics of extended-spectrum cephalosporin-resistant Enterobacteriaceae from humans in the community.

    Directory of Open Access Journals (Sweden)

    Angela H A M van Hoek

    Full Text Available To investigate the molecular characteristics of extended-spectrum cephalosporin (ESC-resistant Enterobacteriaceae collected during a cross-sectional study examining the prevalence and risk factors for faecal carriage of extended-spectrum β-lactamase (ESBL-producing Enterobacteriaceae in humans living in areas with high or low broiler density.ESC-resistant Enterobacteriaceae were identified by combination disc-diffusion test. ESBL/AmpC/carbapenemase genes were analysed using PCR and sequencing. For E. coli, phylogenetic groups and MLST were determined. Plasmids were characterized by transformation and PCR-based replicon typing. Subtyping of plasmids was done by plasmid multilocus sequence typing.175 ESC-resistant Enterobacteriaceae were cultured from 165/1,033 individuals. The isolates were Escherichia coli(n=65, Citrobacter freundii (n=52, Enterobacter cloacae (n=38, Morganella morganii (n=5, Enterobacter aerogenes (n=4, Klebsiella pneumoniae (n=3, Hafnia alvei (n=2, Shigella spp. (n=2, Citrobacter amalonaticus (n=1, Escherichia hermannii (n=1, Kluyvera cryocrescens (n=1, and Pantoea agglomerans (n=1. The following ESBL genes were recovered in 55 isolates originating from 49 of 1,033 (4.7 % persons: blaCTX-M-1 (n=17, blaCTX-M-15 (n=16, blaCTX-M-14 (n=9, blaCTX-M-2 (n=3, blaCTX-M-3 (n=2, blaCTX-M-24 (n=2, blaCTX-M-27 (n=1, blaCTX-M-32 (n=1, blaSHV-12 (n=2, blaSHV-65 (n=1 and blaTEM-52 (n=1. Plasmidic AmpC (pAmpC genes were discovered in 6 out of 1,033 (0.6 % persons. One person carried two different E. coli isolates, one with blaCTX-M-1 and the other with blaCMY-2 and therefore the prevalence of persons carrying Enterobacteriaceae harboring ESBL and/or pAmpC genes was 5.2 %. In eight E. coli isolates the AmpC phenotype was caused by mutations in the AmpC promoter region. No carbapenemase genes were identified. A large variety of E. coli genotypes was found, ST131 and ST10 being most common.ESBL/pAmpC genes resembled those from patients in Dutch

  10. Holistic systems biology approaches to molecular mechanisms of human helper T cell differentiation to functionally distinct subsets.

    Science.gov (United States)

    Chen, Z; Lönnberg, T; Lahesmaa, R

    2013-08-01

    Current knowledge of helper T cell differentiation largely relies on data generated from mouse studies. To develop therapeutical strategies combating human diseases, understanding the molecular mechanisms how human naïve T cells differentiate to functionally distinct T helper (Th) subsets as well as studies on human differentiated Th cell subsets is particularly valuable. Systems biology approaches provide a holistic view of the processes of T helper differentiation, enable discovery of new factors and pathways involved and generation of new hypotheses to be tested to improve our understanding of human Th cell differentiation and immune-mediated diseases. Here, we summarize studies where high-throughput systems biology approaches have been exploited to human primary T cells. These studies reveal new factors and signalling pathways influencing T cell differentiation towards distinct subsets, important for immune regulation. Such information provides new insights into T cell biology and into targeting immune system for therapeutic interventions. © 2013 John Wiley & Sons Ltd.

  11. A comprehensive experiment for molecular biology: Determination of single nucleotide polymorphism in human REV3 gene using PCR-RFLP.

    Science.gov (United States)

    Zhang, Xu; Shao, Meng; Gao, Lu; Zhao, Yuanyuan; Sun, Zixuan; Zhou, Liping; Yan, Yongmin; Shao, Qixiang; Xu, Wenrong; Qian, Hui

    2017-07-08

    Laboratory exercise is helpful for medical students to understand the basic principles of molecular biology and to learn about the practical applications of molecular biology. We have designed a lab course on molecular biology about the determination of single nucleotide polymorphism (SNP) in human REV3 gene, the product of which is a subunit of DNA polymerase ζ and SNPs in this gene are associated with altered susceptibility to cancer. This newly designed experiment is composed of three parts, including genomic DNA extraction, gene amplification by PCR, and genotyping by RFLP. By combining these activities, the students are not only able to learn a series of biotechniques in molecular biology, but also acquire the ability to link the learned knowledge with practical applications. This comprehensive experiment will help the medical students improve the conceptual understanding of SNP and the technical understanding of SNP detection. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(4):299-304, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

  12. Molecular characteristics of Human Endogenous Retrovirus type-W in schizophrenia and bipolar disorder.

    Science.gov (United States)

    Perron, H; Hamdani, N; Faucard, R; Lajnef, M; Jamain, S; Daban-Huard, C; Sarrazin, S; LeGuen, E; Houenou, J; Delavest, M; Moins-Teisserenc, H; Moins-Teiserenc, H; Bengoufa, D; Yolken, R; Madeira, A; Garcia-Montojo, M; Gehin, N; Burgelin, I; Ollagnier, G; Bernard, C; Dumaine, A; Henrion, A; Gombert, A; Le Dudal, K; Charron, D; Krishnamoorthy, R; Tamouza, R; Leboyer, M

    2012-12-04

    Epidemiological and genome-wide association studies of severe psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD), suggest complex interactions between multiple genetic elements and environmental factors. The involvement of genetic elements such as Human Endogenous Retroviruses type 'W' family (HERV-W) has consistently been associated with SZ. HERV-W envelope gene (env) is activated by environmental factors and encodes a protein displaying inflammation and neurotoxicity. The present study addressed the molecular characteristics of HERV-W env in SZ and BD. Hundred and thirty-six patients, 91 with BD, 45 with SZ and 73 healthy controls (HC) were included. HERV-W env transcription was found to be elevated in BD (P<10-4) and in SZ (P=0.012) as compared with HC, but with higher values in BD than in SZ group (P<0.01). The corresponding DNA copy number was paradoxically lower in the genome of patients with BD (P=0.0016) or SZ (P<0.0003) than in HC. Differences in nucleotide sequence of HERV-W env were found between patients with SZ and BD as compared with HC, as well as between SZ and BD. The molecular characteristics of HERV-W env also differ from what was observed in Multiple Sclerosis (MS) and may represent distinct features of the genome of patients with BD and SZ. The seroprevalence for Toxoplasma gondii yielded low but significant association with HERV-W transcriptional level in a subgroup of BD and SZ, suggesting a potential role in particular patients. A global hypothesis of mechanisms inducing such major psychoses is discussed, placing HERV-W at the crossroads between environmental, genetic and immunological factors. Thus, particular infections would act as activators of HERV-W elements in earliest life, resulting in the production of an HERV-W envelope protein, which then stimulates pro-inflammatory and neurotoxic cascades. This hypothesis needs to be further explored as it may yield major changes in our understanding and treatment of

  13. Molecular determinants of acidic pH-dependent transport of human equilibrative nucleoside transporter 3.

    Science.gov (United States)

    Rahman, Md Fazlur; Askwith, Candice; Govindarajan, Rajgopal

    2017-09-08

    Equilibrative nucleoside transporters (ENTs) translocate hydrophilic nucleosides across cellular membranes and are essential for salvage nucleotide synthesis and purinergic signaling. Unlike the prototypic human ENT members hENT1 and hENT2, which mediate plasma membrane nucleoside transport at pH 7.4, hENT3 is an acidic pH-activated lysosomal transporter partially localized to mitochondria. Recent studies demonstrate that hENT3 is indispensable for lysosomal homeostasis, and that mutations in hENT3 can result in a spectrum of lysosomal storage-like disorders. However, despite hENT3's prominent role in lysosome pathophysiology, the molecular basis of hENT3-mediated transport is unknown. Therefore, we sought to examine the mechanistic basis of acidic pH-driven hENT3 nucleoside transport with site-directed mutagenesis, homology modeling, and [(3)H]adenosine flux measurements in mutant RNA-injected Xenopus oocytes. Scanning mutagenesis of putative residues responsible for pH-dependent transport via hENT3 revealed that the ionization states of Asp-219 and Glu-447, and not His, strongly determined the pH-dependent transport permissible-impermissible states of the transporter. Except for substitution with certain isosteric and polar residues, substitution of either Asp-219 or Glu-447 with any other residues resulted in robust activity that was pH-independent. Dual substitution of Asp-219 and Glu-447 to Ala sustained pH-independent activity over a broad range of physiological pH (pH 5.5-7.4), which also maintained stringent substrate selectivity toward endogenous nucleosides and clinically used nucleoside drugs. Our results suggest a putative pH-sensing role for Asp-219 and Glu-447 in hENT3 and that the size, ionization state, or electronegative polarity at these positions is crucial for obligate acidic pH-dependent activity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Neuro-inspired computing using resistive synaptic devices

    CERN Document Server

    2017-01-01

    This book summarizes the recent breakthroughs in hardware implementation of neuro-inspired computing using resistive synaptic devices. The authors describe how two-terminal solid-state resistive memories can emulate synaptic weights in a neural network. Readers will benefit from state-of-the-art summaries of resistive synaptic devices, from the individual cell characteristics to the large-scale array integration. This book also discusses peripheral neuron circuits design challenges and design strategies. Finally, the authors describe the impact of device non-ideal properties (e.g. noise, variation, yield) and their impact on the learning performance at the system-level, using a device-algorithm co-design methodology. • Provides single-source reference to recent breakthroughs in resistive synaptic devices, not only at individual cell-level, but also at integrated array-level; • Includes detailed discussion of the peripheral circuits and array architecture design of the neuro-crossbar system; • Focuses on...

  15. Emerging trends in neuro engineering and neural computation

    CERN Document Server

    Lee, Kendall; Garmestani, Hamid; Lim, Chee

    2017-01-01

    This book focuses on neuro-engineering and neural computing, a multi-disciplinary field of research attracting considerable attention from engineers, neuroscientists, microbiologists and material scientists. It explores a range of topics concerning the design and development of innovative neural and brain interfacing technologies, as well as novel information acquisition and processing algorithms to make sense of the acquired data. The book also highlights emerging trends and advances regarding the applications of neuro-engineering in real-world scenarios, such as neural prostheses, diagnosis of neural degenerative diseases, deep brain stimulation, biosensors, real neural network-inspired artificial neural networks (ANNs) and the predictive modeling of information flows in neuronal networks. The book is broadly divided into three main sections including: current trends in technological developments, neural computation techniques to make sense of the neural behavioral data, and application of these technologie...

  16. ADAPTIVE NEURO-FUZZY INFERENCE SYSTEM FOR END MILLING

    Directory of Open Access Journals (Sweden)

    ANGELOS P. MARKOPOULOS

    2016-09-01

    Full Text Available Soft computing is commonly used as a modelling method in various technological areas. Methods such as Artificial Neural Networks and Fuzzy Logic have found application in manufacturing technology as well. NeuroFuzzy systems, aimed to combine the benefits of both the aforementioned Artificial Intelligence methods, are a subject of research lately as have proven to be superior compared to other methods. In this paper an adaptive neuro-fuzzy inference system for the prediction of surface roughness in end milling is presented. Spindle speed, feed rate, depth of cut and vibrations were used as independent input variables, while roughness parameter Ra as dependent output variable. Several variations are tested and the results of the optimum system are presented. Final results indicate that the proposed model can accurately predict surface roughness, even for input that was not used in training.

  17. Prediction of conductivity by adaptive neuro-fuzzy model.

    Science.gov (United States)

    Akbarzadeh, S; Arof, A K; Ramesh, S; Khanmirzaei, M H; Nor, R M

    2014-01-01

    Electrochemical impedance spectroscopy (EIS) is a key method for the characterizing the ionic and electronic conductivity of materials. One of the requirements of this technique is a model to forecast conductivity in preliminary experiments. The aim of this paper is to examine the prediction of conductivity by neuro-fuzzy inference with basic experimental factors such as temperature, frequency, thickness of the film and weight percentage of salt. In order to provide the optimal sets of fuzzy logic rule bases, the grid partition fuzzy inference method was applied. The validation of the model was tested by four random data sets. To evaluate the validity of the model, eleven statistical features were examined. Statistical analysis of the results clearly shows that modeling with an adaptive neuro-fuzzy is powerful enough for the prediction of conductivity.

  18. A Neuro-psychological Explanation of Religious Experience?

    DEFF Research Database (Denmark)

    Runehov, Anne Leona Cesarine

    2004-01-01

    The search for the basis of religious experience among neurological processes in the brain has resulted in a widespread debate within, as well as outside the academic world. The aim of this paper is to analyse to what extent a neuro-psychological theory could explain the phenomenon of religious...... experience. To clarify what the neuro-psychological studies of the present paper mean by the concept of religious experience, the concept has been divided into three different types: the Erlebnis or RErl type, the Erfahrung or RErf type and the ideological or RIT type of religious experience. In his studies...... and for the problem arising when drawing inadequately reasoned conclusions. Key Words Religious experiences, religious Erlebnis, religious Erfahrung, (religious) ideology, neuroscience, neuropsychology, pain, PET, reductionism, partial reductionism, Transcendental Meditation, epilepsy, schizophrenia....

  19. Seizure prediction using adaptive neuro-fuzzy inference system.

    Science.gov (United States)

    Rabbi, Ahmed F; Azinfar, Leila; Fazel-Rezai, Reza

    2013-01-01

    In this study, we present a neuro-fuzzy approach of seizure prediction from invasive Electroencephalogram (EEG) by applying adaptive neuro-fuzzy inference system (ANFIS). Three nonlinear seizure predictive features were extracted from a patient's data obtained from the European Epilepsy Database, one of the most comprehensive EEG database for epilepsy research. A total of 36 hours of recordings including 7 seizures was used for analysis. The nonlinear features used in this study were similarity index, phase synchronization, and nonlinear interdependence. We designed an ANFIS classifier constructed based on these features as input. Fuzzy if-then rules were generated by the ANFIS classifier using the complex relationship of feature space provided during training. The membership function optimization was conducted based on a hybrid learning algorithm. The proposed method achieved highest sensitivity of 80% with false prediction rate as low as 0.46 per hour.

  20. Is hair loss a reality in neuro-interventional radiology?

    LENUS (Irish Health Repository)

    Gavagan, L

    2012-02-01

    Reports in the literature of radiation-induced hair loss are becoming increasingly common. This work describes a retrospective dose study of patients (n = 958) undergoing diagnostic (primarily cerebral angiograms) and therapeutic (primarily cerebral embolisation) procedures in a neuro-interventional suite. A comparison of patient doses as dose area product (DAP) readings from a single-plane image intensifier system (mean DAP value of 8772 cGy cm(2)) were compared with patient doses from a flat panel biplane system (mean DAP value of 7855 cGy cm(2)). Over 80 % of patients requiring neuro-interventional procedures were found to undergo two procedures or more. An estimated 7 % of therapeutic procedures were found to reach the International Commission on Radiological Protection threshold for temporary epilation.

  1. Prediction of conductivity by adaptive neuro-fuzzy model.

    Directory of Open Access Journals (Sweden)

    S Akbarzadeh

    Full Text Available Electrochemical impedance spectroscopy (EIS is a key method for the characterizing the ionic and electronic conductivity of materials. One of the requirements of this technique is a model to forecast conductivity in preliminary experiments. The aim of this paper is to examine the prediction of conductivity by neuro-fuzzy inference with basic experimental factors such as temperature, frequency, thickness of the film and weight percentage of salt. In order to provide the optimal sets of fuzzy logic rule bases, the grid partition fuzzy inference method was applied. The validation of the model was tested by four random data sets. To evaluate the validity of the model, eleven statistical features were examined. Statistical analysis of the results clearly shows that modeling with an adaptive neuro-fuzzy is powerful enough for the prediction of conductivity.

  2. Space Flight-Associated Neuro-ocular Syndrome.

    Science.gov (United States)

    Lee, Andrew G; Mader, Thomas H; Gibson, C Robert; Tarver, William

    2017-09-01

    New and unique physiologic and pathologic systemic and neuro-ocular responses have been documented in astronauts during and after long-duration space flight. Although the precise cause remains unknown, space flight-associated neuro-ocular syndrome (SANS) has been adopted as an appropriate descriptive term. The Space Medicine Operations Division of the US National Aeronautics and Space Administration (NASA) has documented the variable occurrence of SANS in astronauts returning from long-duration space flight on the International Space Station. These clinical findings have included unilateral and bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and nerve fiber layer infarcts. The clinical findings of SANS have been correlated with structural changes on intraorbital and intracranial magnetic resonance imaging and in-flight and terrestrial ultrasonographic studies and ocular optical coherence tomography. Further study of SANS is ongoing for consideration of future manned missions to space, including a return trip to the moon or Mars.

  3. Aquatic intervention in children with neuro-motor impairments

    OpenAIRE

    Getz, M.D.

    2006-01-01

    The present thesis addresses the influence of aquatic interventions on motor performance of children with neuro-motor deficiencies in a functional context. The theoretical framework is based on a functional approach in compliance to the International Classification of Function and Disability (ICF). Chapter 2 addresses the relationship between motor performance in the aquatic environment setting as measured by the Aquatic Independence Measure (AIM) to motor performance on land as measured by t...

  4. Neuro-expert system applications in power systems

    Energy Technology Data Exchange (ETDEWEB)

    Khosla, R.; Dillon, T.

    1997-12-31

    In this chapter we outline a generic neuro-expert system (GENUES) architecture for hybrid reasoning. The architecture consists of five phases, namely, decomposition phase, control phase, decision phase, preprocessing phase, and postprocessing phase. The architecture is particularly applicable in time critical diagnostic/classification domains and data intensive domains in general. We describe the application of GENUES in a real time alarm processing system in a power system control centre. (Author)

  5. Cognitive rehabilitation in neuro-oncological patients: three case reports

    Directory of Open Access Journals (Sweden)

    Chiara Zucchella

    2012-06-01

    Full Text Available Cognitive impairment is one of the most common neurological disorders in neuro-oncological patients, linked with morbidity, disability, and poor quality of life. As pharmacologic interventions have not yet proven effective in the treatment of cognitive deficits, cognitive rehabilitation could represent an alternative approach. This paper presents three case studies, describing the cognitive intervention and discussing its effectiveness in the light of current evidence.

  6. Ultrastructural muscle and neuro-muscular junction alterations in polymyositis

    Directory of Open Access Journals (Sweden)

    L. L. Babakova

    2012-01-01

    Full Text Available Ultrastructural analysis of 7 biopsies from m.palmaris longus and m.deltoideus in patients with confirmed polymyositis revealed alterationand degeneration of muscle fibers and anomalies of neuro-muscular junction (NMJ. The NMJ abnormalities and following denervation ofmuscle fibers in polymyositis start with subsynaptic damages. The occurance of regeneration features in muscle fibers at any stage is characteristic for PM.

  7. Cognitive rehabilitation of schizophrenia through NeuroVr training.

    Science.gov (United States)

    La Paglia, Filippo; La Cascia, Caterina; Rizzo, Rosalinda; Sideli, Lucia; Francomano, Antonio; La Barbera, Daniele

    2013-01-01

    Cognitive difficulties are prevalent in people with diagnosis of schizophrenia and are associated with poor long-term functioning. In particular, memory, selective, divided and sustained attention and executive functions are altered by this disease. We used a Virtual Reality environment (developed via the NeuroVr2.0 software) for the rehabilitation of shifting, sustained attention and action planning functions using tasks reminiscent of daily life tasks. Test and retest showed significant differences in the assessed cognitive dimensions.

  8. Hybrid Neuro-Fuzzy Classifier Based On Nefclass Model

    Directory of Open Access Journals (Sweden)

    Bogdan Gliwa

    2011-01-01

    Full Text Available The paper presents hybrid neuro-fuzzy classifier, based on NEFCLASS model, which wasmodified. The presented classifier was compared to popular classifiers – neural networks andk-nearest neighbours. Efficiency of modifications in classifier was compared with methodsused in original model NEFCLASS (learning methods. Accuracy of classifier was testedusing 3 datasets from UCI Machine Learning Repository: iris, wine and breast cancer wisconsin.Moreover, influence of ensemble classification methods on classification accuracy waspresented.

  9. Connexin-dependent signaling in neuro-hormonal systems.

    OpenAIRE

    Potolicchio Ilaria; Cigliola Valentina; Velazquez-Garcia Silvia; Klee Philippe; Valjevac Amina; Kapic Dina; Cosovic Esad; Lepara Orhan; Hadzovic-Dzuvo Almira; Mornjacovic Zakira; Meda Paolo

    2011-01-01

    The advent of multicellular organisms was accompanied by the development of short and long range chemical signalling systems including those provided by the nervous and endocrine systems. In turn the cells of these two systems have developed mechanisms for interacting with both adjacent and distant cells. With evolution such mechanisms have diversified to become integrated in a complex regulatory network whereby individual endocrine and neuro endocrine cells sense the state of activity of th...

  10. Neuro-fuzzy controller to navigate an unmanned vehicle.

    Science.gov (United States)

    Selma, Boumediene; Chouraqui, Samira

    2013-12-01

    A Neuro-fuzzy control method for an Unmanned Vehicle (UV) simulation is described. The objective is guiding an autonomous vehicle to a desired destination along a desired path in an environment characterized by a terrain and a set of distinct objects, such as obstacles like donkey traffic lights and cars circulating in the trajectory. The autonomous navigate ability and road following precision are mainly influenced by its control strategy and real-time control performance. Fuzzy Logic Controller can very well describe the desired system behavior with simple "if-then" relations owing the designer to derive "if-then" rules manually by trial and error. On the other hand, Neural Networks perform function approximation of a system but cannot interpret the solution obtained neither check if its solution is plausible. The two approaches are complementary. Combining them, Neural Networks will allow learning capability while Fuzzy-Logic will bring knowledge representation (Neuro-Fuzzy). In this paper, an artificial neural network fuzzy inference system (ANFIS) controller is described and implemented to navigate the autonomous vehicle. Results show several improvements in the control system adjusted by neuro-fuzzy techniques in comparison to the previous methods like Artificial Neural Network (ANN).

  11. A novel Neuro-fuzzy classification technique for data mining

    Directory of Open Access Journals (Sweden)

    Soumadip Ghosh

    2014-11-01

    Full Text Available In our study, we proposed a novel Neuro-fuzzy classification technique for data mining. The inputs to the Neuro-fuzzy classification system were fuzzified by applying generalized bell-shaped membership function. The proposed method utilized a fuzzification matrix in which the input patterns were associated with a degree of membership to different classes. Based on the value of degree of membership a pattern would be attributed to a specific category or class. We applied our method to ten benchmark data sets from the UCI machine learning repository for classification. Our objective was to analyze the proposed method and, therefore compare its performance with two powerful supervised classification algorithms Radial Basis Function Neural Network (RBFNN and Adaptive Neuro-fuzzy Inference System (ANFIS. We assessed the performance of these classification methods in terms of different performance measures such as accuracy, root-mean-square error, kappa statistic, true positive rate, false positive rate, precision, recall, and f-measure. In every aspect the proposed method proved to be superior to RBFNN and ANFIS algorithms.

  12. ORGANIZATIONAL NEURO STUDIES AND ETHICAL CONSIDERATIONS

    OpenAIRE

    YOĞUN, Ayse ESMERAY

    2016-01-01

    Cognitive neuroscience as a multidisciplinary field, seeks to understand human behavior at the intersection of social, cognitive, and neural spheres of science. Neuroscience can help organizations become more effective by support productivity and employee satisfaction. With this paper, it is aimed to contribute to literature with the potential promise of cognitive side of organizational behavior as synergic young field. The main aim of this paper is to discuss neuroscience techniques and ongo...

  13. Molecular Epidemiology of Human Enterovirus Associated with Aseptic Meningitis in Shandong Province, China, 2006–2012

    Science.gov (United States)

    Liu, Guifang; Xu, Aiqiang; Lin, Xiaojuan; Song, Lizhi; Ji, Feng; Wang, Suting; Cui, Ning; Song, Yanyan

    2014-01-01

    Background Human enteroviruses (HEVs) are common causes of acute meningitis. However, there is limited information about HEV associated with aseptic meningitis in mainland China because it has not been classified as a notifiable disease. Objectives To characterize the HEVs associated with sporadic aseptic meningitis in China and to analyze their genetic features. Study Design Cerebrospinal fluid, throat swab and feces specimens were collected from patients with aseptic meningitis in 5 sentinel hospitals in Shandong Province, China between 2006 and 2012. Virological investigation (viral isolation and molecular identification) and phylogenetic analysis were performed. Results A total of 437 hospitalized patients were reported, and enteroviruses were detected in the specimens from 84 patients (19.2%) and were identified into 17 serotypes. The nine main serotypes were echovirus (E) 30 (27.4%), EV71 (13.1%), coxsackievirus (CV) B1 (9.5%), CVB3 (7.1%), CVB5 (7.1%), E6 (7.1%), E9 (7.1%), CVA9 (6.0%), and CVA10 (3.6%). Monthly distribution of isolated enteroviruses revealed a major peak in summer-fall season and a small second peak in winter constituted totally by EV71. Sequence analysis on VP1 coding region suggested Shandong strains had great genetic divergence with isolates from other countries. Conclusions Multiple serotypes were responsible for enterovirus meningitis in mainland China. Aseptic meningitis caused by EV71 and coxsackie A viruses–the predominant pathogens for the hand, foot, and mouth disease–is currently an important concern in mainland China. PMID:24587020

  14. Molecular epidemiology of human enterovirus associated with aseptic meningitis in Shandong Province, China, 2006-2012.

    Directory of Open Access Journals (Sweden)

    Zexin Tao

    Full Text Available BACKGROUND: Human enteroviruses (HEVs are common causes of acute meningitis. However, there is limited information about HEV associated with aseptic meningitis in mainland China because it has not been classified as a notifiable disease. OBJECTIVES: To characterize the HEVs associated with sporadic aseptic meningitis in China and to analyze their genetic features. STUDY DESIGN: Cerebrospinal fluid, throat swab and feces specimens were collected from patients with aseptic meningitis in 5 sentinel hospitals in Shandong Province, China between 2006 and 2012. Virological investigation (viral isolation and molecular identification and phylogenetic analysis were performed. RESULTS: A total of 437 hospitalized patients were reported, and enteroviruses were detected in the specimens from 84 patients (19.2% and were identified into 17 serotypes. The nine main serotypes were echovirus (E 30 (27.4%, EV71 (13.1%, coxsackievirus (CV B1 (9.5%, CVB3 (7.1%, CVB5 (7.1%, E6 (7.1%, E9 (7.1%, CVA9 (6.0%, and CVA10 (3.6%. Monthly distribution of isolated enteroviruses revealed a major peak in summer-fall season and a small second peak in winter constituted totally by EV71. Sequence analysis on VP1 coding region suggested Shandong strains had great genetic divergence with isolates from other countries. CONCLUSIONS: Multiple serotypes were responsible for enterovirus meningitis in mainland China. Aseptic meningitis caused by EV71 and coxsackie A viruses-the predominant pathogens for the hand, foot, and mouth disease-is currently an important concern in mainland China.

  15. Genetic diversity and molecular evolution of the major human metapneumovirus surface glycoproteins over a decade.

    Science.gov (United States)

    Papenburg, Jesse; Carbonneau, Julie; Isabel, Sandra; Bergeron, Michel G; Williams, John V; De Serres, Gaston; Hamelin, Marie-Ève; Boivin, Guy

    2013-11-01

    Human metapneumovirus (HMPV) is a recently discovered paramyxovirus that is a major cause of respiratory infections worldwide. We aim to describe the molecular evolution of the HMPV F (fusion) and G (attachment) surface glycoproteins because they are targets for vaccines, monoclonal antibodies and antivirals currently in development. Nasopharyngeal aspirates were collected in children <3 years old with acute respiratory infection in Quebec City during 2001-2010. HMPV-positive samples (n = 163) underwent HMPV-F and -G gene sequencing. Furthermore, HMPV-F (n = 124) and -G (n = 217) sequences were obtained from GenBank and other studies. Evolutionary analyses (phylogenetic reconstruction, sequence identity, detection of recombination and adaptive evolution) were computed. Sequences clustered into 5 genetic lineages (A1, A2a, A2b, B1 and B2). Multiple lineages circulated each year in Quebec City. With the exception of B1, each of the 5 subgroups was the predominant lineage during ≥1 season. The A1 lineage was not detected since 2002-2003 in our local cohort. There was no evidence of inter- or intragenic recombination. HMPV-F was highly conserved, whereas HMPV-G exhibited greater diversity. HMPV-F demonstrated strong evidence of purifying selection, both overall and in an abundance of negatively selected amino acid sites. In contrast, sites under diversifying selection were detected in all HMPV-G lineages (range, 4-15), all of which were located in the ectodomain. Predominant circulating HMPV lineages vary by year. HMPV-F is highly constrained and undergoes significant purifying selection. Given its high genetic variability, we found a modest number of positively selected sites in HMPV-G. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Molecular Characterisation of Small Molecule Agonists Effect on the Human Glucagon Like Peptide-1 Receptor Internalisation.

    Directory of Open Access Journals (Sweden)

    Aiysha Thompson

    Full Text Available The glucagon-like peptide receptor (GLP-1R, which is a G-protein coupled receptor (GPCR, signals through both Gαs and Gαq coupled pathways and ERK phosphorylation to stimulate insulin secretion. The aim of this study was to determine molecular details of the effect of small molecule agonists, compounds 2 and B, on GLP-1R mediated cAMP production, intracellular Ca2+ accumulation, ERK phosphorylation and its internalisation. In human GLP-1R (hGLP-1R expressing cells, compounds 2 and B induced cAMP production but caused no intracellular Ca2+ accumulation, ERK phosphorylation or hGLP-1R internalisation. GLP-1 antagonists Ex(9-39 and JANT-4 and the orthosteric binding site mutation (V36A in hGLP-1R failed to inhibit compounds 2 and B induced cAMP production, confirming that their binding site distinct from the GLP-1 binding site on GLP-1R. However, K334A mutation of hGLP-1R, which affects Gαs coupling, inhibited GLP-1 as well as compounds 2 and B induced cAMP production, indicating that GLP-1, compounds 2 and B binding induce similar conformational changes in the GLP-1R for Gαs coupling. Additionally, compound 2 or B binding to the hGLP-1R had significantly reduced GLP-1 induced intracellular Ca2+ accumulation, ERK phosphorylation and hGLP-1R internalisation. This study illustrates pharmacology of differential activation of GLP-1R by GLP-1 and compounds 2 and B.

  17. Molecular evolution of the fusion protein (F) gene in human respiratory syncytial virus subgroup B.

    Science.gov (United States)

    Kimura, Hirokazu; Nagasawa, Koo; Kimura, Ryusuke; Tsukagoshi, Hiroyuki; Matsushima, Yuki; Fujita, Kiyotaka; Hirano, Eiko; Ishiwada, Naruhiko; Misaki, Takako; Oishi, Kazunori; Kuroda, Makoto; Ryo, Akihide

    2017-08-01

    In this study, we examined the molecular evolution of the fusion protein (F) gene in human respiratory syncytial virus subgroup B (HRSV-B). First, we performed time-scale evolution analyses using the Bayesian Markov chain Monte Carlo (MCMC) method. Next, we performed genetic distance, linear B-cell epitope prediction, N-glycosylation, positive/negative selection site, and Bayesian skyline plot analyses. We also constructed a structural model of the F protein and mapped the amino acid substitutions and the predicted B-cell epitopes. The MCMC-constructed phylogenetic tree indicated that the HRSV F gene diverged from the bovine respiratory syncytial virus gene approximately 580years ago and had a relatively low evolutionary rate (7.14×10(-4)substitutions/site/year). Furthermore, a common ancestor of HRSV-A and -B diverged approximately 290years ago, while HRSV-B diverged into three clusters for approximately 60years. The genetic similarity of the present strains was very high. Although a maximum of 11 amino acid substitutions were observed in the structural model of the F protein, only one strain possessed an amino acid substitution located within the palivizumab epitope. Four epitopes were predicted, although these did not correspond to the neutralization sites of the F protein including the palivizumab epitope. In addition, five N-glycosylation sites of the present HRSV-B strains were inferred. No positive selection sites were identified; however, many sites were found to be under negative selection. The effective population size of the gene has remained almost constant. On the basis of these results, it can be concluded that the HRSV-B F gene is highly conserved, as is the F protein of HRSV-A. Moreover, our prediction of B-cell epitopes does not show that the palivizumab reaction site may be recognized as an epitope during naturally occurring infections. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Molecular Characterization of Human Respiratory Syncytial Virus in the Philippines, 2012-2013.

    Directory of Open Access Journals (Sweden)

    Rungnapa Malasao

    Full Text Available Human respiratory syncytial virus (HRSV is a major cause of acute lower respiratory tract infections in infants and children worldwide. We performed molecular analysis of HRSV among infants and children with clinical diagnosis of severe pneumonia in four study sites in the Philippines, including Biliran, Leyte, Palawan, and Metro Manila from June 2012 to July 2013. Nasopharyngeal swabs were collected and screened for HRSV using real-time polymerase chain reaction (PCR. Positive samples were tested by conventional PCR and sequenced for the second hypervariable region (2nd HVR of the G gene. Among a total of 1,505 samples, 423 samples were positive for HRSV (28.1%, of which 305 (72.1% and 118 (27.9% were identified as HRSV-A and HRSV-B, respectively. Two genotypes of HRSV-A, NA1 and ON1, were identified during the study period. The novel ON1 genotype with a 72-nucleotide duplication in 2nd HVR of the G gene increased rapidly and finally became the predominant genotype in 2013 with an evolutionary rate higher than the NA1 genotype. Moreover, in the ON1 genotype, we found positive selection at amino acid position 274 (p<0.05 and massive O- and N-glycosylation in the 2nd HVR of the G gene. Among HRSV-B, BA9 was the predominant genotype circulating in the Philippines. However, two sporadic cases of GB2 genotype were found, which might share a common ancestor with other Asian strains. These findings suggest that HRSV is an important cause of severe acute respiratory infection among children in the Philippines and revealed the emergence and subsequent predominance of the ON1 genotype and the sporadic detection of the GB2 genotype. Both genotypes were detected for the first time in the Philippines.

  19. Adsorption of human serum albumin: Dependence on molecular architecture of the oppositely charged surface

    Science.gov (United States)

    Sukhishvili, Svetlana A.; Granick, Steve

    1999-05-01

    We contrast the adsorption of human serum albumin (HSA) onto two solid substrates previously primed with the same polyelectrolyte of net opposite charge to form one of two alternative structures: randomly adsorbed polymer and the "brush" configuration. These structures were formed either by the adsorption of quaternized poly-4-vinylpyridine (QPVP) or by end-grafting QPVP chains of the same chemical makeup and the same molecular weight to surfaces onto which QPVP segments did not adsorb. The adsorption of HSA was quantified by using Fourier transform infrared spectroscopy in attenuated total reflection (FTIR-ATR). The two substrates showed striking differences with regard to HSA adsorption. First, the brush substrate induced lesser perturbations in the secondary structure of the adsorbed HSA, reflecting easier conformational adjustment for longer free segments of polyelectrolyte upon binding with the protein. Second, the penetration of HSA into the brush substrate was kinetically retarded relative to the randomly adsorbed polymer, probably due to both pore size restriction and electrostatic sticking between charged groups of HSA and QPVP molecules. Third, release of HSA from the adsorbed layer, as the ionic strength was increased from a low level up to the high level of 1 M NaCl, was largely inhibited for the brush substrate, but occurred easily and rapidly for the substrate with statistically adsorbed QPVP chains. Finally, even after addition of a strong polymeric adsorption competitor (sodium polystyrene sulfonate), HSA remained trapped within a brush substrate though it desorbed slowly from the preadsorbed QPVP layer. This method to produce irreversible trapping of the protein within a brush substrate without major conformational change may find application in biosensor design.

  20. [Molecular detection of human papillomavirus in women with cervical condylomas treated with trichloroacetic acid].

    Science.gov (United States)

    Cortés Gutiérrez, Elva I; Witvrun Avila, Joel N; Sánchez Rodríguez, Glafir; Gaspar Belmonte, José A; Hernández Garza, Fernando; Cerda Flores, Ricardo M

    2005-03-01

    1) To determinate the presence of human papillomavirus (HPV) in women with cervical condylomas after the trichloroacetic acid application by the polymerase chain reaction (PCR) test, and 2) to validate the colposcopy test versus the PCR (gold standard). A selected sample of 28 women of 18 to 45 years old with cervical condyloma acuminate, without evidence of cervical neoplasic lesion and with positive diagnosis of HPV with PCR was included. beta-globin gene was used as internal control and as DNA integrity marker. Women included in this study were divided in: treated group (n = 14), which were treated just one time with trichloroacetic acid to 90% in the cervix, the cul de sacs and the vagina areas, and placebo group (n = 14), which were treated with physiological saline. After eight weeks of being applied the treatment, each one of the 28 women was HPV diagnosed again by colposcopy and PCR. All women amplified for the beta-globin gene. In the treated group, 11/14 (78%) patients did not show amplification. The colposcopy showed two negative false, five positive false, one positive true and six negative true tests, revealing sensitivity of 33.33% and specificity of 54.54%. From the molecular point of view, this study showed that the trichloroacetic acid application causes physical destruction of the infected tissue, without detecting DNA damage due to the cellular desquamation. On the other hand, the colposcopy regarding the PCR is not an appropriate test for the diagnosis and follow-up of the HPV infection.

  1. Molecular spectroscopic studies examining the interactions between phenobarbital and human serum albumin in alcohol consumption.

    Science.gov (United States)

    Cui, Sheng-Feng; Li, Wei; Zhou, Cheng-He

    2017-11-02

    Alcohol dependence is associated with a wide range of serious mental, physical, and social consequences and is one of the most common chronic diseases worldwide. Barbiturates, which are a first-line treatment in the clinic for alcohol withdrawal, may result in combined barbiturate and alcohol use. Their co-use abuse may promote synergistic effects between barbiturates and alcohol in vivo. To investigate the effects of different alcohol concentrations on the synergistic effects of phenobarbital and alcohol. The interactions between phenobarbital and human serum albumin (HSA) and the effects of different alcohol concentrations on the binding behaviors of the phenobarbital-HSA system were investigated by molecular docking and spectroscopic methods, including fluorescence spectroscopy and UV-visible absorption spectroscopy. Experimental results revealed that phenobarbital can be stored and carried by HSA. The presence of alcohol (≤1.96 × 10(-2) M) can increase the proportion of free phenobarbital and shorten the half-life and storage time of phenobarbital in the blood, thereby enhancing its bioactive efficacy. The binding constants (Kb) of the phenobarbital-HSA system decrease in the presence of alcohol (≥2.61 × 10(-2) M), which suggests that phenobarbital should be quickly cleared from blood, thereby decreasing the activity of phenobarbital. The effects of alcohol on the transposition of phenobarbital by HSA at the beginning of the barbiturate metabolic process play an important role in the synergistic effects of phenobarbital and alcohol. This mechanism may be significant for the clinical dosage of patients with alcohol dependence.

  2. Molecular identification of 7 human papillomavirus types in recurrent respiratory papillomatosis.

    Science.gov (United States)

    Peñaloza-Plascencia, M; Montoya-Fuentes, H; Flores-Martínez, S E; Fierro-Velasco, F J; Peñaloza-González, J M; Sánchez-Corona, J

    2000-09-01

    Recurrent respiratory papillomatosis (RRP) is the most frequent benign neoplasm in childhood; it originates as a mild dysphonia and results in asphyxia. The RRP has been associated with an infection caused by human papillomavirus (HPV), mainly types 6 and 11, the latter being associated with more severe RRP. To analyze the frequency of the association of RRP with the HPV types in our juvenile population and to classify it according to severity. Observational descriptive trial. Forty-seven samples of paraffin-embedded papillomas, from 26 female and 21 male children (age range, 2 weeks to 17 years) were analyzed. DNA was isolated and a 188-base pair fragment was amplified from a consensus sequence in the E1 open reading frame of several HPVs by polymerase chain reaction. The corresponding band was recovered and reamplified. The fragment was digested with the restriction enzyme RsaI. The digestion products were compared with patterns of molecular weight markers for viral type identification. The patients' clinical records were reviewed, and RRP was classified as mild or aggressive. The presence of HPV types 6, 11, 16, 31, 33, 35, or 39 was confirmed in all the cases with different combinations. The chi(2) test showed no significant differences in clinical aggressiveness among the viral types. A logistic regression analysis demonstrated no association between clinical aggressiveness and any viral type or viral combination. These results show that RRP is caused by infection with HPV types 6 and 11 in addition to many other types, with no relationship between HPV type and clinical severity.

  3. Molecular dynamics simulations of human serum albumin and role of disulfide bonds.

    Science.gov (United States)

    Castellanos, Maria Monica; Colina, Coray M

    2013-10-10

    Atomistic molecular dynamics simulations of human serum albumin in the presence and absence of disulfide bonds are presented. Simulations of 70 ns duration provide information on the relevance of disulfide bonds in the dynamics and structural conformation of HSA. Significant conformational changes are observed in the absence of disulfide bonds after 35 ns that could impact the functionality and stability of the protein. Changes in the secondary structure, hydrogen bonds, B factors, and cross-correlations reveal which disulfide bonds are important for keeping the secondary and tertiary structure and dynamics of the protein (e.g., Cys168-Cys177, Cys278-Cys289) and which have little effect on the local structure and dynamics (e.g., Cys200-Cys246, Cys461-Cys477). Removing all disulfide bonds in the protein appears to be a practical prescreening tool for identifying disulfide bonds relevant to structure and dynamics. In the absence of disulfide bonds, certain hydrogen bonds and correlated motions vanish, affecting the structure of neighboring residues. The structure of the primary binding sites of HSA is partially affected when disulfide bonds are removed. For the native structure, simulations clearly reveal the conformational changes that allow the only free cysteine to be exposed on the protein surface to form intermolecular disulfide bonds; this information could not be resolved from the static crystal structure alone. The absence of specific disulfide bonds could lead to partially unfolded structures; such structures are known to be prone to protein aggregation. Removing disulfide bonds could have similar consequences in other proteins of interest, such as immunoglobulin G.

  4. Molecular epidemiology of human rhinovirus infections in the pediatric emergency department.

    Science.gov (United States)

    Martin, Emily K; Kuypers, Jane; Chu, Helen Y; Lacombe, Kirsten; Qin, Xuan; Strelitz, Bonnie; Bradford, Miranda; Jones, Charla; Klein, Eileen J; Englund, Janet A

    2015-01-01

    Human rhinovirus (HRV) infections are highly prevalent, genetically diverse, and associated with both mild upper respiratory tract and more severe lower tract illnesses (LRTI). To characterize the molecular epidemiology of HRV infections in young children seeking acute medical care. Nasal swabs collected from symptomatic children FilmArray(®)) for multiple viruses including HRV/enterovirus. HRV-positive results were confirmed by laboratory-developed real-time reverse transcription PCR (LD-PCR). Clinical data were collected by chart review. A subset of samples was selected for sequencing using the 5' noncoding region. Associations between LRTI and HRV species and genotypes were estimated using logistic regression analysis. Of 595 samples with HRV/enterovirus detected by FilmArray, 474 (80%) were confirmed as HRV by LD-PCR. 211 (96%) of 218 selected samples were sequenced; HRV species A, B, and C were identified in 133 (63%), 6 (3%), and 72 (34%), respectively. LRTI was more common in HRV-C than HRV-A illness episodes (adjusted OR [95% CI] 2.35[1.03-5.35). Specific HRV-A and HRV-C genotypes detected in multiple patients were associated with a greater proportion of LRTI episodes. In 18 patients with >1 HRV-positive illness episodes, a distinct genotype was detected in each. Diverse HRV genotypes circulated among symptomatic children during the study period. We found an association between HRV-C infections and LRTI in this patient population and evidence of association between specific HRV genotypes and LRTI. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Molecular detection of human papillomavirus and viral DNA load after radiotherapy for cervical carcinomas.

    Science.gov (United States)

    Kahla, Saloua; Kochbati, Lotfi; Sarraj, Sana; Ben Daya, Imen; Maalej, Mongi; Oueslati, Ridha

    2016-10-13

    Infection with high-risk types of human papillomavirus (HPV) is a necessary cause for cervical carcinoma. Radiation therapy together with surgery is the most effective treatment. The purpose of this study was to investigate the molecular basis of the response to radiotherapy in cervical cancer cells. Tumor cells were obtained from biopsies of 44 cervical cancers, collected before and after radiotherapy. The presence of HPV was analyzed by polymerase chain reaction (PCR) using primers specific for the L1 region. The prevalence of HPV was 70.4%, with HPV16 being the most common (54.5%) and HPV18 the second (15.9%). Our analyses show that ionizing radiation does not influence HPV detection, as the percentage of HPV-positive biopsies was similar in patients before and after radiotherapy (HPV16 60% vs. 51.7% and HPV18 20% vs. 13.7%, respectively). However, the detection of HPV did vary by tumor stage, with the highest proportion observed in late-stage tumors (HPV16 and HPV18 in 80% and 60% of stage III tumors, respectively). We also found that HPV viral load is influenced by radiotherapy and tumor stage, with the highest viral loads in late-stage tumors (stage III) after 1 day since radiotherapy (p<0.05). According to Kaplan-Meier curves, higher HPV viral load was associated with significantly shortened progression-free survival (p = 0.04). Our data provide prospective evidence that ionizing radiation can affect the HPV viral load and this might offer the best strategies for assessment of therapeutic efficacy.

  6. Molecular targets for the protodynamic action of cis-urocanic acid in human bladder carcinoma cells

    Directory of Open Access Journals (Sweden)

    Laihia Jarmo K

    2010-10-01

    Full Text Available Abstract Background cis-urocanic acid (cis-UCA is an endogenous amino acid metabolite capable of transporting protons from the mildly acidic extracellular medium into the cell cytosol. The resulting intracellular acidification suppresses many cellular activities. The current study was aimed at characterizing the molecular mechanisms underlying cis-UCA-mediated cytotoxicity in cultured cancer cells. Methods 5367 bladder carcinoma cells were left untreated or treated with cis-UCA. Cell death was assessed by measuring caspase-3 activity, mitochondrial membrane polarization, formation and release of cytoplasmic histone-associated DNA fragments, and cellular permeabilization. Cell viability and metabolic activity were monitored by colorimetric assays. Nuclear labelling was used to quantify the effects of cis-UCA on cell cycle. The activity of the ERK and JNK signalling pathways was studied by immunoblotting with specific antibodies. Phosphatase activity in cis-UCA-treated cells was determined by assay kits measuring absorbance resulting from the dephosphorylation of an artificial substrate. All statistical analyses were performed using the two-way Student's t-test (p Results Here we report that treatment of the 5637 human bladder carcinoma cells with 2% cis-UCA induces both apoptotic and necrotic cell death. In addition, metabolic activity of the 5637 cells is rapidly impaired, and the cells arrest in cell cycle in response to cis-UCA. Importantly, we show that cis-UCA promotes the ERK and JNK signalling pathways by efficiently inhibiting the activity of serine/threonine and tyrosine phosphatases. Conclusions Our studies elucidate how cis-UCA modulates several cellular processes, thereby inhibiting the proliferation and survival of bladder carcinoma cells. These anti-cancer effects make cis-UCA a potential candidate for the treatment of non-muscle invasive bladder carcinoma.

  7. Molecular and clinical characterization of human respiratory syncytial virus in South Korea between 2009 and 2014.

    Science.gov (United States)

    Park, E; Park, P H; Huh, J W; Yun, H J; Lee, H K; Yoon, M H; Lee, S; Ko, G

    2017-11-01

    Respiratory syncytial virus (RSV) can cause serious respiratory infections, second only to influenza virus. In order to know RSV's genetic changes we examined 4028 respiratory specimens from local hospital outpatients in Gyeonggi Province, South Korea over six consecutive years by real-time one-step RT-PCR; 183 patients were positive for RSV infection. To investigate the specific distribution of RSV genotypes, we performed partial sequencing of the glycoprotein gene. Of the 131 RSV-A specimens sequenced, 61 (43·3%) belonged to the ON1 genotype, 66 (46·8%) were NA1 genotype, 3 (2·1%) were GA5 genotype, and 1 (0·7%) belonged to the GA1 genotype. Of the 31 RSV-B specimens sequenced, 29 were BA9 genotype (87·9%) and 2 were BA10 genotype (6·1%). The most common clinical symptoms were fever, cough, nasal discharge, and phlegm; multiple logistic regression analysis showed that RSV-positive infection on pediatric patients was strongly associated with cough (OR = 2·8, 95% CI 1·6-5·1) and wheezing (OR = 2·8, 95% CI 1·7-4·4). The ON1 genotype was significantly associated with phlegm (OR = 11·8, 95% CI 3·8-46·7), while the NA1 genotype was associated with the pediatric patients' gender (males, OR = 2·4, 95% CI 1·1-5·4) and presence of chills (OR = 5·1, 95% CI 1·1-27·2). RSV subgroup B was showed association with nasal obstruction (OR = 4·6, 95% CI 1·2-20·0). The majority of respiratory virus coinfections with RSV were human rhinovirus (47·2%). This study contributes to our understanding of the molecular epidemiological characteristics of RSV, which promotes the potential for improving RSV vaccines.

  8. Object-Oriented NeuroSys: Parallel Programs for Simulating Large Networks of Biologically Accurate Neurons

    Energy Technology Data Exchange (ETDEWEB)

    Pacheco, P; Miller, P; Kim, J; Leese, T; Zabiyaka, Y

    2003-05-07

    Object-oriented NeuroSys (ooNeuroSys) is a collection of programs for simulating very large networks of biologically accurate neurons on distributed memory parallel computers. It includes two principle programs: ooNeuroSys, a parallel program for solving the large systems of ordinary differential equations arising from the interconnected neurons, and Neurondiz, a parallel program for visualizing the results of ooNeuroSys. Both programs are designed to be run on clusters and use the MPI library to obtain parallelism. ooNeuroSys also includes an easy-to-use Python interface. This interface allows neuroscientists to quickly develop and test complex neuron models. Both ooNeuroSys and Neurondiz have a design that allows for both high performance and relative ease of maintenance.

  9. Molecular imaging correlates of tryptophan metabolism via the kynurenine pathway in human meningiomas.

    Science.gov (United States)

    Bosnyák, Edit; Kamson, David O; Guastella, Anthony R; Varadarajan, Kaushik; Robinette, Natasha L; Kupsky, William J; Muzik, Otto; Michelhaugh, Sharon K; Mittal, Sandeep; Juhász, Csaba

    2015-09-01

    Increased tryptophan metabolism via the kynurenine pathway (KP) is a key mechanism of tumoral immune suppression in gliomas. However, details of tryptophan metabolism in meningiomas have not been elucidated. In this study, we evaluated in vivo tryptophan metabolism in meningiomas and compared it with gliomas using α-[(11)C]-methyl-L-tryptophan (AMT)-PET. We also explored expression patterns of KP enzymes in resected meningiomas. Forty-seven patients with MRI-detected meningioma (n = 16) and glioma (n = 31) underwent presurgical AMT-PET scanning. Tumoral AMT uptake and tracer kinetic parameters (including K and k3' evaluating unidirectional uptake and trapping, respectively) were measured, correlated with meningioma grade, and compared between meningiomas and gliomas. Patterns of KP enzyme expression were assessed by immunohistochemistry in all meningiomas. Meningioma grade showed a positive correlation with AMT k3' tumor/cortex ratio (r = 0.75, P = .003), and this PET parameter distinguished grade I from grade II/III meningiomas with 92% accuracy. Kinetic AMT parameters could differentiate meningiomas from both low-grade gliomas (97% accuracy by k3' ratios) and high-grade gliomas (83% accuracy by K ratios). Among 3 initial KP enzymes (indoleamine 2,3-dioxygenase 1/2, and tryptophan 2,3-dioxygenase 2 [TDO2]), TDO2 showed the strongest immunostaining, particularly in grade I meningiomas. TDO2 also showed a strong negative correlation with AMT k3' ratios (P = .001). PET imaging of tryptophan metabolism can provide quantitative imaging markers for differentiating grade I from grade II/III meningiomas. TDO2 may be an important driver of in vivo tryptophan metabolism in these tumors. These results can have implications for pharmacological targeting of the KP in meningiomas. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Neuro-Behçet’s disease in childhood: A focus on the neuro-ophthalmological features

    Directory of Open Access Journals (Sweden)

    Mora Paolo

    2013-01-01

    Full Text Available Abstract Neuro-Behçet’s disease (NBD involves the central nervous system; peripheral nervous system involvement is not often reported. NBD is quite common in adult patients and occurs rarely during childhood and adolescence. Young patients may share symptoms and signs of NBD with other neuro-ophthalmological disorders (e.g. idiopathic intracranial hypertension; thus, making the differential diagnosis difficult. Neuroimaging is mandatory and necessary for a correct NBD diagnosis but in children radiological examinations are often difficult to perform without sedation. From 1971 to 2011, 130 patients aged ≤16 years have been reported with NBD, according to retrospective surveys, case series, and case reports. The origin of the reported cases met the well-known geographical distribution of Behçet’s disease (BD; the mean age at presentation of neurological findings was 11.8 years, with male gender prevalence (ratio, 2.9:1. We considered in detail the neuro-ophthalmological features of the 53 cases whose neuroimaging alterations were described with an assigned radiological pattern of the disease (parenchymal: 14 cases, non-parechymal: 35 cases, and mixed: 4 cases. In 19/53 patients (36%, neuro-ophthalmological symptoms anticipated any pathognomonic sign for a BD diagnosis, or only occasional aphtae were recalled by the patients. Family history was positive in 17% of subjects. Headache was reported in 75% of the patients; in those presenting with cerebral vascular involvement, headache was combined to other symptoms of intracranial hypertension. Papilledema was the most frequently reported ophthalmological finding, followed by posterior uveitis. Treatment consisted of systemic steroids in 93% of patients, often combined with other immunosuppressive drugs (especially colchicine and azathioprine. Clinical recovery or improvement was documented in the large majority of patients. Nine subjects had definitive alterations, and one died. Based on our

  11. Molecular and physiological actions of quercetin: need for clinical trials to assess its benefits in human disease.

    Science.gov (United States)

    Miles, Sarah L; McFarland, Margaret; Niles, Richard M

    2014-11-01

    There is a growing realization that natural products such as phytochemicals can be used in diets or as supplements to prevent or treat human disease. The disciplines of epidemiology, pharmacognosy, and molecular biology have provided evidence that certain dietary constituents decrease blood pressure, influence immune and neuronal function, affect the incidence of cancer, and ameliorate the abnormal properties of cancer cells. Molecular studies have uncovered the interesting feature that most phytochemicals have multiple modes of action. This review focuses on the flavonoid phytochemical quercetin and describes the myriad of conditions in which quercetin affects a number of physiological processes. Despite the compelling information available, including a number of animal studies, translation of these findings into human clinical trials has been slow. The status of current clinical research on quercetin is summarized, and direction for further research is suggested. © 2014 International Life Sciences Institute.

  12. Different molecular organization of two carotenoids, lutein and zeaxanthin, in human colon epithelial cells and colon adenocarcinoma cells

    Science.gov (United States)

    Grudzinski, Wojciech; Piet, Mateusz; Luchowski, Rafal; Reszczynska, Emilia; Welc, Renata; Paduch, Roman; Gruszecki, Wieslaw I.

    2018-01-01

    Two cell lines, human normal colon epithelial cells (CCD 841 CoTr) and human colon adenocarcinoma cells (HT-29) were cultured in the presence of exogenous carotenoids, either zeaxanthin or lutein. Both carotenoids demonstrated cytotoxicity with respect to cancer cells but not to normal cells. Cells from both the cell lines were analyzed with application of fluorescence lifetime imaging microscopy and Raman scattering microscopy. Both imaging techniques show effective incorporation of carotenoid molecules into growing cells. Comparison of the Raman scattering and fluorescence lifetime characteristics reveals different molecular organization of carotenoids in the carcinoma and normal cells. The main difference consists in a carotenoid aggregation level which is substantially lower in the carcinoma cells as compared to the normal cells. Different molecular organization of carotenoids was interpreted in terms of a different metabolism of normal and carcinoma cells and has been concluded to provide a possibility of cancer diagnosis based on spectroscopic analyses.

  13. Evidence-based Neuro Linguistic Psychotherapy: a meta-analysis.

    Science.gov (United States)

    Zaharia, Cătălin; Reiner, Melita; Schütz, Peter

    2015-12-01

    Neuro Linguistic Programming (NLP) Framework has enjoyed enormous popularity in the field of applied psychology. NLP has been used in business, education, law, medicine and psychotherapy to identify people's patterns and alter their responses to stimuli, so they are better able to regulate their environment and themselves. NLP looks at achieving goals, creating stable relationships, eliminating barriers such as fears and phobias, building self-confidence, and self-esteem, and achieving peak performance. Neuro Linguistic Psychotherapy (NLPt) encompasses NLP as framework and set of interventions in the treatment of individuals with different psychological and/or social problems. We aimed systematically to analyse the available data regarding the effectiveness of Neuro Linguistic Psychotherapy (NLPt). The present work is a meta-analysis of studies, observational or randomized controlled trials, for evaluating the efficacy of Neuro Linguistic Programming in individuals with different psychological and/or social problems. The databases searched to identify studies in English and German language: CENTRAL in the Cochrane Library; PubMed; ISI Web of Knowledge (include results also from Medline and the Web of Science); PsycINFO (including PsycARTICLES); Psyndex; Deutschsprachige Diplomarbeiten der Psychologie (database of theses in Psychology in German language), Social SciSearch; National library of health and two NLP-specific research databases: one from the NLP Community (http://www.nlp.de/cgi-bin/research/nlprdb.cgi?action=res_entries) and one from the NLP Group (http://www.nlpgrup.com/bilimselarastirmalar/bilimsel-arastirmalar-4.html#Zweig154). From a total number of 425 studies, 350 were removed and considered not relevant based on the title and abstract. Included, in the final analysis, are 12 studies with numbers of participants ranging between 12 and 115 subjects. The vast majority of studies were prospective observational. The actual paper represents the first

  14. Study of interaction of butyl p-hydroxybenzoate with human serum albumin by molecular modeling and multi-spectroscopic method

    Energy Technology Data Exchange (ETDEWEB)

    Wang Qin, E-mail: wqing07@lzu.c [Department of Chemistry, Lanzhou University, Lanzhou 730000 (China); Zhang Yaheng, E-mail: zhangyah04@lzu.c [Department of Chemistry, Lanzhou University, Lanzhou 730000 (China); Sun Huijun, E-mail: sun.hui.jun-04@163.co [Department of Chemistry, Lanzhou University, Lanzhou 730000 (China); Chen Hongli, E-mail: hlchen@lzu.edu.c [Department of Chemistry, Lanzhou University, Lanzhou 730000 (China); Chen Xingguo, E-mail: chenxg@lzu.edu.c [Department of Chemistry, Lanzhou University, Lanzhou 730000 (China)

    2011-02-15

    Study of the interaction between butyl p-hydroxybenzoate (butoben) and human serum albumin (HSA) has been performed by molecular modeling and multi-spectroscopic method. The interaction mechanism was predicted through molecular modeling first, then the binding parameters were confirmed using a series of spectroscopic methods, including fluorescence spectroscopy, UV-visible absorbance spectroscopy, circular dichroism (CD) spectroscopy and Fourier transform infrared (FT-IR) spectroscopy. The thermodynamic parameters of the reaction, standard enthalpy {Delta}H{sup 0} and entropy {Delta}S{sup 0}, have been calculated to be -29.52 kJ mol{sup -1} and -24.23 J mol{sup -1} K{sup -1}, respectively, according to the Van't Hoff equation, which suggests the van der Waals force and hydrogen bonds are the predominant intermolecular forces in stabilizing the butoben-HSA complex. Results obtained by spectroscopic methods are consistent with that of the molecular modeling study. In addition, alteration of secondary structure of HSA in the presence of butoben was evaluated using the data obtained from UV-visible absorbance, CD and FT-IR spectroscopies. - Research highlights: The interaction between butyl p-hydroxybenzoate with HSA has been investigated for the first time. Molecular modeling study can provide theoretical direction for experimental design. Multi-spectroscopic method can provide the binding parameters and thermodynamic parameters. These results are important for food safety and human health when using parabens as a preservative.

  15. [Establishment of diagnosis and treatment patterns of holistic integrated medicine for neuro-ophthalmology].

    Science.gov (United States)

    Wang, Yanling

    2014-12-01

    Neuro-ophthalmology, as an interdisciplinary, covers at least three disciplines- ophthalmology, neurology and neurosurgery. With limited knowledge in each discipline, doctors often make misdiagnoses for neuro-ophthalmology diseases. Therefore, it is imperative to abandon the distinction between disciplines and combine all the knowledge to diagnose and treat patients in patterns of holistic integrated medicine in order to effectively improve the diagnosis and treatment of neuro-ophthalmology.

  16. Hemiballismus Secondary to Neuro-Behçet Disease: Case Report

    OpenAIRE

    Turgay Demir; Şebnem Bıçakçı; Miray Erdem

    2014-01-01

    Behçet’s Disease is a multisystemic, inflammatory, recurrent disorder with oral and genital ulcerations along with cutaneous and opthalmic symptoms. Central nervous involvement called Neuro-Behçet is one of the clinical forms of Behçet’s Disease. Extrapyramidal findings are rare in Neuro-Behçet. We report here a case with Neuro-Behçet disease presented with acute hemiballismus.

  17. MI-ANFIS: A Multiple Instance Adaptive Neuro-Fuzzy Inference System

    Science.gov (United States)

    2015-08-02

    Instance AdaptiveNeuro- Fuzzy Inference System We introduce a novel adaptive neuro- fuzzy architecture based on the framework of Multiple Instance Fuzzy ...Inference. The new architecture called Multiple Instance-ANFIS (MI-ANFIS), is an extension of the standard Adaptive Neuro Fuzzy Inference System (ANFIS... Fuzzy Inference REPORT DOCUMENTATION PAGE 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 10. SPONSOR/MONITOR’S ACRONYM(S) ARO 8. PERFORMING

  18. MOLECULAR CHARACTERIZATION BY USING RANDOM AMPLIFIED POLYMORPHIC DNA (RAPD ANALYSIS OF SALMONELLA ENTERITIDIS ISOLATES RECOVERED FROM AVIAN AND HUMAN SOURCES

    Directory of Open Access Journals (Sweden)

    E. YAQOOB, I. HUSSAIN AND S. U. RAHMAN

    2007-04-01

    Full Text Available Random amplified polymorphic DNA (RAPD analysis was applied for molecular characterization of five Salmonella enteritidis strains from different avian sources and human cases of infection. A total of 16 primers were used and only five primers showed good discriminatory power for all five isolates. Dendrogram showed a common lineage among all five isolates. There was a close genetic relationship among isolates of eggs and human sources, while there was less pronounced homology among isolates of broiler meat and human sources. On the basis of results we have found that an endemic strain of S. enteritidis is prevalent between the poultry derived food and humans which gives us an insight to genetic diversity of S. enteritidis from these sources.

  19. Characterization of Enterobius vermicularis in a human population, employing a molecular-based method from adhesive tape samples.

    Science.gov (United States)

    Piperaki, Evangelia-Theophano; Spanakos, Gregory; Patsantara, Giannoula; Vassalou, Evdokia; Vakalis, Nikolaos; Tsakris, Athanassios

    2011-01-01

    Human infection with the parasitic nematode Enterobius vermicularis occurs worldwide, particularly in children. Although its prevalence may exceed 35% in some parts of the world, molecular studies of E. vermicularis in humans are limited. The aim of the present study was to investigate the genetic variation within E. vermicularis in a human population. For this purpose, 77 adhesive tape samples taken from Greek children infested with E. vermicularis were tested. New primers were designed to amplify a segment of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of E. vermicularis from adhesive tape samples. Thirty-six amplicons were sequenced and eleven different haplotypes were identified. All sequences clustered within the type previously characterized (type B), only reported to date from captive chimpanzees. To the best of our knowledge, this is the first study of E. vermicularis genotypes from a human population. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. A Molecular Dynamics Approach to Ligand-Receptor Interaction in the Aspirin-Human Serum Albumin Complex

    OpenAIRE

    Alvarez, H. Ariel; McCarthy, Andrés N.; Grigera, J. Raúl

    2012-01-01

    In this work, we present a study of the interaction between human serum albumin (HSA) and acetylsalicylic acid (ASA, C9H8O4) by molecular dynamics simulations (MD). Starting from an experimentally resolved structure of the complex, we performed the extraction of the ligand by means of the application of an external force. After stabilization of the system, we quantified the force used to remove the ASA from its specific site of binding to HSA and calculated the mechanical nonequilibrium exter...